Complement Receptor Deficiency

Complement receptor deficiency is a rare health problem where the body does not have enough working “complement receptors” on its immune cells, or these receptors do not work properly. Complement receptors are tiny proteins that sit on the surface of white blood cells, red blood cells, and other cells. They help the immune system see and grab germs that have been marked (opsonized) by the complement system. When the receptors are missing or weak, the immune system cannot clear germs and immune complexes well, so infections and autoimmune problems can happen more easily. [1]

Complement receptor deficiency is a very rare inherited immune problem where important “complement receptors” on white blood cells or B cells do not work properly or are missing. These receptors (for example CR1/CD35, CR2/CD21, CR3/CD11b–CD18 and CR4/CD11c–CD18) normally help immune cells grab and swallow bacteria that have been tagged by complement proteins, and they also help clear immune complexes and shape antibody responses. When these receptors are defective, people can have repeated skin and lung infections, gum disease, and sometimes autoimmune diseases like lupus, because germs are not cleared well and immune complexes can build up.

The complement system is a group of more than 30 blood proteins that act like “helper soldiers” for the immune system. They coat bacteria, help kill them, attract immune cells, and clean away dead cells and immune complexes. Complement receptors (such as CR1, CR2, CR3, and CR4) are like “locks” that recognize these coated germs and waste. If the locks are missing or broken, the coated germs and waste cannot be removed properly. [2]

Because complement receptor deficiency is so uncommon, there is no single “magic” drug that cures the receptor defect. Treatment is usually based on general principles used for primary immunodeficiency and complement disorders: strong infection prevention, early antibiotics, vaccination, sometimes immunoglobulin (IgG) replacement, and in the most severe forms related to CD18 (leukocyte adhesion deficiency type I) curative bone-marrow transplant (HSCT).

Because of this problem, people with complement receptor deficiency may get repeated bacterial infections, especially of the skin, mouth, lungs, or blood. They may also have a higher chance of autoimmune diseases, where the immune system attacks the body’s own tissues, such as lupus or some types of arthritis. These patterns are known from studies on complement deficiencies and on low or abnormal CR1 and CR2 expression in autoimmune disease and immunodeficiency. [3]

Another names

Doctors do not always use one single name for complement receptor deficiency. Different names may be used in books and articles because several complement receptors can be affected. Some possible names you may see include: [1]

• Complement receptor defect or complement receptor disorder. [1]

• CR1 deficiency (complement receptor 1 deficiency). [2]

• CR2 deficiency (CD21 deficiency). [3]

• CR3 functional deficiency (often part of leukocyte adhesion deficiency type 1, due to CD18 problems). [4]

• CR4 functional deficiency (also linked to CD18 problems). [4]

These names point to the same basic idea: the receptors that should bind complement-coated material do not work normally, which changes how the immune system reacts to germs and immune complexes. [2]

Types of complement receptor deficiency

There is no single standard list of types, but doctors often think about which receptor is affected and how. Most information comes from research on CR1, CR2, CR3, and CR4, plus clinical reports of CD21 deficiency and of CD18 defects that damage CR3 and CR4 function. [1]

• CR1 (CD35) deficiency or low CR1 expression
  CR1 is found on red blood cells, white blood cells, and other cells. It helps clear immune complexes and control complement activation. Low CR1 levels have been linked with systemic lupus erythematosus (SLE) and other autoimmune diseases in several studies. When CR1 is reduced, immune complexes are not cleared well and can deposit in tissues. [2]

• CR2 (CD21) deficiency
  CR2 is found mainly on B cells. It helps B cells respond to germs coated with complement and supports normal antibody responses. True genetic CD21 (CR2) deficiency is rare but has been reported in families with low antibodies (hypogammaglobulinemia), recurrent infections, and autoimmunity. [3]

• CR3 (CD11b/CD18) functional deficiency
  CR3 is a β2-integrin (CD11b/CD18) on neutrophils, monocytes, and natural killer cells. It binds iC3b on germs and helps phagocytosis (engulfing). Failure to make CD18 leads to loss of CR3 and is part of leukocyte adhesion deficiency type 1, which causes severe, recurrent bacterial and skin infections and poor wound healing. [4]

• CR4 (CD11c/CD18) functional deficiency
  CR4 (CD11c/CD18) is related to CR3 and also uses CD18. It participates in binding complement-coated particles and in cell adhesion. When CD18 is missing, CR4 cannot form correctly, which further weakens phagocytosis and immune cell trafficking. [4]

• Combined low CR1/CR2 expression
  Some patients, especially with SLE or other autoimmune conditions, show low levels of both CR1 and CR2 on B cells or red cells. This is sometimes described as complement receptor deficiency in the context of autoimmune disease, and it may contribute to poor clearance of immune complexes and abnormal B-cell activation. [5]

• Secondary or acquired complement receptor deficiency
  In some conditions, the genes are normal, but chronic inflammation, infections, or immune activation change how much receptor is present or how it works. This can be seen in chronic autoimmune diseases or severe infections. In these cases, the receptor problem is secondary to another disease. [6]

Causes of complement receptor deficiency

There are many possible reasons why complement receptors may be too few or not working well. Some are inherited (genetic), and some are acquired later in life. For many people, more than one factor may be involved. [1]

1. Inherited mutations in CR1 (CD35) gene
   Changes in the CR1 gene can lower CR1 levels or change its structure. This may reduce immune complex clearance and can increase the risk of autoimmune diseases like SLE in some people. [2]

2. Inherited mutations in CR2 (CD21) gene
   Rare families have mutations in the CD21 gene that cause real CD21 deficiency. These patients can have low antibodies, recurrent infections, and autoimmunity. [3]

3. Mutations in ITGAM (CD11b) affecting CR3
   ITGAM encodes CD11b, part of CR3. Some variants change CR3 function and are linked with autoimmune diseases like SLE, showing how genetic changes in CR3 can disturb immune control. [4]

4. Mutations in ITGB2 (CD18) gene
   ITGB2 encodes CD18, which pairs with CD11b and CD11c to form CR3 and CR4. Mutations cause leukocyte adhesion deficiency type 1. In this disorder, CR3 and CR4 cannot be expressed, leading to a practical complement receptor deficiency on phagocytes. [5]

5. Other inherited inborn errors of immunity
   Some broader immune gene defects can indirectly lower complement receptor expression or function. These inborn errors may be grouped with primary immunodeficiencies that affect innate immunity and complement pathways. [6]

6. Chronic systemic lupus erythematosus (SLE)
   In SLE, immune complexes form and use up complement. Many studies show reduced CR1 and CR2 expression on cells in SLE, which can worsen immune complex problems and tissue damage. [7]

7. Other autoimmune diseases (e.g., rheumatoid arthritis, Sjögren syndrome)
   Autoimmune diseases such as rheumatoid arthritis and Sjögren syndrome have been linked with changes in CR1 and CR2 levels on B cells and other cells, which may change immune responses and complex clearance. [8]

8. Chronic immune complex–mediated diseases
   Conditions with many circulating immune complexes (for example some vasculitides or cryoglobulinemia) may lead to down-regulation or exhaustion of complement receptors on cells that constantly handle these complexes. [9]

9. Severe or repeated bacterial infections
   Strong or long-lasting infections can alter expression of complement receptors on immune cells as part of the inflammatory response, sometimes lowering receptor levels temporarily or functionally. [10]

10. Chronic viral infections
    Some viruses act on B cells or other immune cells and may change CR2 or other receptors on their surface, which can disturb complement receptor function and immune regulation. [11]

11. Bone marrow failure or dysplasia
    Diseases like myelodysplastic syndromes can produce abnormal immune cells with altered surface receptor patterns, including complement receptors, which may lower effective receptor numbers. [12]

12. Medications that affect immune cells
    Some drugs that suppress or modulate the immune system may change receptor expression on white blood cells, including complement receptors, as part of their effect on cell activation and trafficking. [13]

13. Chronic kidney or liver disease
    Chronic organ disease can disturb complement production, immune complex handling, and receptor expression, because the liver and spleen are important for removing complement-coated complexes. [14]

14. Nutritional deficiencies
    Severe long-term lack of key nutrients (such as protein, some vitamins, and trace elements) can weaken bone marrow and immune function in general and may lower receptor expression indirectly. [15]

15. Uncontrolled chronic inflammation
    Ongoing inflammation in the body can cause continuous activation and internalization of receptors on immune cells. Over time, this can reduce receptors on the surface, including complement receptors. [16]

16. Aging of the immune system (immunosenescence)
    With age, immune cells often show changes in receptor patterns and function. Complement receptor expression and function may decline as part of this process, contributing to weaker clearance of germs and immune complexes. [17]

17. Malignancies of blood cells (e.g., some leukemias, lymphomas)
    Cancer cells of the blood or lymph system may show abnormal or reduced expression of complement receptors, and treatments like chemotherapy can further disturb receptor patterns on remaining normal cells. [18]

18. Secondary to complement protein deficiencies
    In people who already have complement protein deficiencies, chronic changes in complement activation and complex handling can secondarily change receptor expression or function, acting like a partial receptor deficiency. [19]

19. Environmental toxins and smoking
    Long-term exposure to toxins, including cigarette smoke, can damage the bone marrow and immune cells and may indirectly affect receptor expression and function. [20]

20. Unknown or multifactorial causes
    In some patients with low complement receptor expression, no clear cause is found. It may be due to a mix of subtle genetic variants and environmental triggers that together disturb receptor production or function. [21]

Symptoms of complement receptor deficiency

Symptoms can be different from person to person, depending on which receptor is affected, how severe the problem is, and whether there are other immune defects. Many signs come from repeated infections and from autoimmune disease. [1]

1. Repeated bacterial infections
   People may get the same types of infections again and again, such as chest infections, skin infections, sinus infections, or ear infections. These infections may start early in life and come back often. [2]

2. Severe or unusual infections
   Some infections can be more serious than usual, for example bloodstream infections or deep tissue infections. This can happen because phagocytes cannot easily grab and kill complement-coated germs without working receptors. [3]

3. Slow wound healing and easy skin infections
   In people with CR3/CR4 problems (for example due to CD18 defects), wounds may heal slowly, and the skin around wounds or the gums may get infected and inflamed very often. [4]

4. Chronic gum disease (gingivitis) and mouth infections
   Recurrent swelling, bleeding gums, and mouth ulcers can appear because the local immune defense in the mouth is weak when phagocytes cannot use complement receptors well. [5]

5. Frequent respiratory infections
   People may have repeated bronchitis, pneumonia, or chronic cough. Poor clearance of complement-coated bacteria and immune complexes in the lungs may lead to ongoing damage. [6]

6. Enlarged lymph nodes or spleen
   Lymph nodes and the spleen are key organs for filtering germs and immune complexes. In some patients, these organs may become enlarged due to chronic immune activation and storage of complexes. [7]

7. Features of autoimmune diseases (e.g., lupus-like symptoms)
   Symptoms like joint pain, rash, kidney problems, or fatigue can appear if immune complexes build up and the immune system attacks self-tissues, as seen in SLE and related diseases linked with CR1/CR2 changes. [8]

8. Low antibody levels and poor vaccine responses (especially with CD21 deficiency)
   Some people with CD21 deficiency have low immunoglobulin levels and respond poorly to vaccines. They may get infections even after vaccination because B cells cannot use CR2 properly. [9]

9. Fatigue and poor growth in children
   Long-term infections and chronic inflammation can lead to tiredness, weight loss, or poor growth in children, as the body spends much energy fighting infections. [10]

10. Fever that comes back often
    A person may have repeated episodes of fever without a clear cause, or fever with each new infection, showing that the immune system is often active. [11]

11. Skin rashes or vasculitic spots
    Small red or purple spots on the skin (purpura), or other rashes, can occur if immune complexes deposit in small blood vessels and cause inflammation. [12]

12. Kidney problems from immune complex deposition
    Protein in the urine, swelling of legs, or high blood pressure may appear if immune complexes build up in the kidneys, as happens in some complement-related autoimmune diseases. [13]

13. Joint pain and swelling
    Joint pain, stiffness, and swelling can occur if immune complexes and inflammation affect the joints, like in lupus or rheumatoid arthritis, which are connected with CR1/CR2 changes in some patients. [14]

14. Breathing problems from chronic lung damage
    After many infections, the lung tissue and airways may become damaged (for example bronchiectasis). This can cause long-term breathlessness and cough. [15]

15. Symptoms of related primary immunodeficiency
    Since complement receptor problems may be part of a wider immunodeficiency, symptoms such as chronic diarrhea, unusual viral or fungal infections, or failure to thrive may also be seen in some patients. [16]

Diagnostic tests for complement receptor deficiency

There is no single simple test that says “you have complement receptor deficiency.” Doctors usually look at the full story: symptoms, physical exam, infection pattern, autoimmune signs, lab tests of blood cells, complement levels, receptor expression, and sometimes genetic tests. Many points below are based on how doctors investigate complement deficiencies and inborn errors of immunity in general. [1]

Physical exam–based tests

1. Full general physical examination
   The doctor looks at the whole body, checks weight, height, breathing, skin, and joints. They look for signs of repeated infections, rash, enlarged lymph nodes, or organ enlargement. This exam gives important early clues that the immune system or complement system may not be working well. [2]

2. Vital signs check (temperature, heart rate, breathing rate, blood pressure)
   Vital signs help show if there is an active infection or chronic illness. Repeated fevers or low blood pressure in infections can suggest serious immune problems, including complement pathway issues. [3]

3. Skin and mucous membrane inspection
   The doctor looks carefully at the skin, mouth, gums, and nose for scars from old infections, current pustules, ulcers, or vasculitic spots. Recurrent skin and mucosal infections are common in phagocytic and complement disorders, and may point toward a receptor problem. [4]

4. Palpation of lymph nodes, liver, and spleen
   Feeling the neck, armpit, groin nodes, and the left upper abdomen (for spleen) helps detect organ enlargement. Enlarged nodes and spleen can reflect chronic immune activation and immune complex storage, as seen in complement and receptor defects. [5]

5. Growth and development assessment in children
   Measuring height and weight and comparing them to age charts helps detect poor growth. Chronic infections or immune disease from complement receptor problems can slow growth over time. [6]

Manual clinical tests

6. Otoscopy and sinus examination
   Looking into the ears with an otoscope and examining the nose and sinuses helps find repeated middle ear infections or chronic sinusitis, which are common in antibody and complement-related problems. [7]

7. Detailed oral and dental examination
   Inspecting teeth and gums for gingivitis, periodontitis, and mouth ulcers is important, especially in CR3/CR4-related problems where severe gum disease and recurrent mouth infections are reported. [8]

8. Chest examination with stethoscope
   Listening to the lungs and tapping the chest can show signs of pneumonia, chronic bronchitis, or bronchiectasis. Frequent abnormal findings may point to an underlying immune or complement problem. [9]

9. Joint examination for swelling and tenderness
   The doctor gently moves and presses on joints to check for pain, fluid, or limited motion. Joint problems may suggest associated autoimmune disease like lupus or arthritis in patients with complement receptor changes. [10]

10. Basic neurologic bedside tests
    Simple tests of reflexes, strength, sensation, and balance can show if there is nerve involvement, which can occur in some immune complex–mediated vasculitic diseases linked to complement problems. [11]

Laboratory and pathological tests

11. Complete blood count (CBC) with differential
    The CBC checks red cells, white cells, and platelets. In complement receptor deficiencies, the total counts may be normal or may show infection-related changes, but the pattern of recurrent infections guides doctors to study the immune system more. [12]

12. Quantitative immunoglobulins (IgG, IgA, IgM, sometimes IgE)
    This blood test measures levels of main antibodies. In CD21 (CR2) deficiency, low immunoglobulin levels and poor vaccine responses may be seen, helping to confirm a combined receptor and antibody problem. [13]

13. Specific antibody responses to vaccines
    Doctors may measure antibody levels after standard vaccines (e.g., pneumococcal). Poor responses can point to B-cell and complement receptor issues, especially when CD21 is involved. [14]

14. Total complement activity (CH50 and AH50 tests)
    CH50 (classical pathway) and AH50 (alternative pathway) tests measure how well the complement proteins work together. In pure receptor deficiency, these may be normal, but in combined complement and receptor problems they can be low. These tests help separate protein defects from receptor defects. [15]

15. Measurement of individual complement components (e.g., C3, C4)
    Blood levels of C3, C4, and other components can show if complement is being used up by immune complexes. Low C3 or C4 with normal or low receptor levels supports a diagnosis involving complement pathways and immune complex disease. [16]

16. Flow cytometry for complement receptor expression (CR1, CR2, CR3, CR4)
    Flow cytometry uses fluorescent antibodies to measure how much of each receptor is present on different blood cells. This is a key test for complement receptor deficiency, and has been used to show CD21 deficiency, low CR1 in SLE, and loss of CR3/CR4 in CD18 defects. [17]

17. Neutrophil phagocytosis and oxidative burst tests
    Functional tests examine how well neutrophils can engulf and kill bacteria. In CR3/CR4-related problems, phagocytosis of complement-coated particles may be reduced, even if other killing pathways are partly intact. [18]

18. Genetic testing for complement receptor and CD18 genes
    DNA tests can look for mutations in genes like CR2 (CD21), ITGAM (CD11b), and ITGB2 (CD18). Identifying a clear genetic change helps confirm an inherited complement receptor deficiency, especially in families with several affected members. [19]

Electrodiagnostic tests

19. Nerve conduction studies and electromyography (EMG)
    If a person has numbness, weakness, or tingling, nerve conduction tests can check for nerve damage, which can happen in some immune complex vasculitides related to complement problems. These tests are not specific for receptor deficiency, but they help assess complications. [20]

20. Electrocardiogram (ECG)
    An ECG records heart electrical activity. In patients with systemic autoimmune disease linked to complement receptor abnormalities, ECG can help detect heart involvement, such as myocarditis or arrhythmias. Again, it is not specific but helps assess organ damage. [21]

Imaging tests

21. Chest X-ray
    Chest X-ray is often done to look for pneumonia, chronic lung changes, or bronchiectasis in people with repeated respiratory infections. Repeated lung problems suggest an underlying immune or complement pathway issue. [22]

22. High-resolution CT scan of the chest
    CT scans give a more detailed view of the lungs and airways. They help detect bronchiectasis and scarring caused by long-standing infections in immunodeficient patients, including those with complement-related defects. [23]

23. Ultrasound or CT of abdomen (liver and spleen)
    Imaging of the abdomen checks liver and spleen size and structure. Enlargement can reflect chronic immune complex handling and immune activation related to complement and receptor problems. [24]

Non-pharmacological (non-drug) treatments

1. Individual infection-prevention plan
Doctors usually create a personalized infection-prevention plan for people with complement receptor deficiency. This plan may include written instructions on what to do at the first sign of fever, when to go to hospital, and which emergency antibiotics are recommended. Having a clear plan helps reduce delays in treatment and lowers the risk of serious sepsis.

2. Up-to-date vaccinations
Although vaccines are not drugs in the usual sense, they are a cornerstone of care. People are usually given inactivated vaccines against pneumococcus, meningococcus, Haemophilus influenzae type b (Hib) and seasonal influenza, and boosters are kept current. This is especially important because complement defects increase risk from encapsulated bacteria like Neisseria and Streptococcus.

3. Household vaccination and “cocooning”
Doctors often recommend that family members and close contacts are also well vaccinated so they are less likely to bring serious infections home. This “cocooning” strategy lowers exposure to dangerous germs for the patient, similar to approaches used in other serious immunodeficiencies.

4. Early-warning fever education
Patients and caregivers are taught that any fever (for example ≥38°C) can be serious. They learn to check temperature correctly, recognize red-flag symptoms (fast breathing, confusion, severe pain), and seek urgent care quickly instead of “waiting to see.” Education like this has been shown to improve outcomes in many primary immunodeficiencies.

5. Meticulous hand and respiratory hygiene
Regular handwashing with soap, use of alcohol hand rubs, covering coughs and wearing masks in crowded or high-risk places can significantly reduce respiratory infections. This is especially useful for people whose complement receptors cannot help phagocytes bind and remove bacteria and viruses efficiently.

6. Avoiding tobacco smoke and air pollution
Smoke and pollution irritate airways and damage the natural defense of the lungs. In a person whose neutrophils already have trouble grabbing opsonized germs because of CR3/CR4 problems, this extra irritation can make pneumonia more likely. Avoiding smoking and second-hand smoke is strongly recommended.

7. Dental and gum-disease prevention
Complement receptor problems linked to CD18 and CR3 are associated with severe gingivitis and periodontitis, because neutrophils cannot migrate properly to the gums. Regular dental check-ups, professional cleaning, daily flossing and antiseptic mouthwashes can reduce bacteria in the mouth and prevent tooth loss and jaw infections.

8. Skin care and wound protection
Because skin infections (boils, abscesses, cellulitis) are common, patients are advised to treat cuts and scrapes quickly with cleaning and dressings, avoid picking at the skin, and seek medical review for redness or pus. Good skin hygiene reduces the bacterial load and gives the immune system a better chance despite receptor defects.

9. Chest physiotherapy and airway clearance
If recurrent chest infections lead to chronic cough or bronchiectasis, breathing exercises, chest physiotherapy, postural drainage and sometimes home devices (flutter valves, oscillating PEP) help move mucus out of the lungs. Removing mucus reduces bacterial growth in damaged airways.

10. Nasal and sinus care
People with frequent sinus infections may benefit from saline rinses, nasal sprays and allergen control. These steps lower mucus stasis in the sinuses, making it harder for bacteria to multiply and cause chronic sinusitis, which is common in antibody and complement-related defects.

11. Written antibiotic “rescue pack” plan
Some immunologists provide a written plan for “stand-by” antibiotics for use at home when travel to hospital is delayed, especially in remote areas. The exact antibiotics and rules are individualized. The goal is to shorten the time from first fever or chest symptoms to effective treatment, but always under clear medical instructions.

12. Regular follow-up with an immunologist
Scheduled visits with an immunology specialist allow ongoing review of infections, lung function, autoimmunity and vaccine responses. Treatment like immunoglobulin replacement or prophylactic antibiotics is adjusted based on clinical course, not just lab tests.

13. Family genetic counseling and testing
Because complement receptor deficiency is usually inherited (often autosomal recessive involving genes such as ITGB2 for CD18), families may benefit from genetic counseling. This helps them understand recurrence risk, screening of siblings, and options for future pregnancies.

14. Infection-action medical alert card
Many centers give patients a card or bracelet stating that they have a serious immunodeficiency and need urgent assessment and broad-spectrum antibiotics if they present with fever or sepsis signs. This helps emergency teams act quickly even if they do not know the patient’s full history.

15. Physiotherapy and exercise program
Gentle, regular exercise improves lung expansion, circulation and general fitness, which support better recovery from infections. A physiotherapist can design a safe program that avoids over-fatigue but keeps muscles and lungs active.

16. Mental-health and social support
Living with a rare immunodeficiency and recurrent infections can cause anxiety, low mood and school or work disruption. Counseling, support groups and psychological support help patients cope and stick to complex treatment plans.

17. Infection-control planning for school or work
Doctors may help write letters to schools or employers guiding when the person should stay home (for example, during outbreaks of meningococcal or influenza infection) and what precautions to use. This reduces exposure while maintaining as normal a life as possible.

18. Travel medicine planning
Before travel, especially to areas with high infectious-disease burdens, immunologists may adjust vaccines, provide emergency antibiotics, and give specific advice on food and water safety. This is important because travel infections can be unusually severe in complement-related disorders.

19. Strict food-safety and hygiene practices
Avoiding undercooked meat, unpasteurized milk and unsafe water lowers the risk of gastrointestinal infections. Because complement receptor defects compromise bacterial clearance, avoiding food-borne pathogens is an important daily non-drug strategy.

20. Comprehensive written care plan
A written care plan summarizing diagnosis, baseline lab results, current medicines, allergies and emergency instructions is invaluable. It helps all doctors involved (family doctor, emergency team, dentist, surgeon) make safe and consistent decisions quickly.

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Drug treatments

There is no specific drug that directly repairs complement receptors. Drug therapy focuses on preventing and treating infections, replacing missing antibody function when present, and managing autoimmune or inflammatory complications. All doses below are typical ranges from prescribing information for primary immunodeficiency or standard use, not individual advice.

1. Intravenous immune globulin (IVIG – general class)
Class: Polyclonal IgG replacement. Typical dose: About 300–600 mg/kg every 3–4 weeks IV in primary immunodeficiency; adjusted to keep IgG levels and infections under control. Purpose: Provides ready-made antibodies when B-cell function is reduced or vaccine responses are weak. Mechanism: IgG antibodies coat bacteria and viruses, helping phagocytes that still function to clear them despite receptor problems. Side effects: Headache, chills, flu-like symptoms, rare thrombosis or kidney problems.

2. Gammagard Liquid (a branded IVIG product)
Class: Immune globulin IV (Human). Dose: 300–600 mg/kg every 3–4 weeks for primary immunodeficiency, based on clinical response. Time: Slow IV infusion in hospital or infusion center. Mechanism: Same as IVIG class, with broad IgG coverage. Side effects: Infusion reactions, aseptic meningitis, rare serious thrombotic events.

3. Gamunex-C (IVIG)
Class: Immune globulin IV/subcutaneous. Dose: 300–600 mg/kg IV every 3–4 weeks for primary humoral immunodeficiency. Purpose: Reduce serious bacterial infections. Mechanism: Supplies functional IgG to compensate for poor opsonization and B-cell help. Side effects: Infusion reactions, headache, thrombotic events, rare kidney injury.

4. Privigen (IVIG)
Class: Immune globulin IV. Dose: 200–800 mg/kg every 3–4 weeks in primary immunodeficiency. Purpose: Long-term infection prevention. Mechanism: Maintains protective IgG trough levels so infections are less frequent and less severe. Side effects: Similar to other IVIGs – headache, fever, rash, rare thrombotic and renal risks.

5. Asceniv (IVIG)
Class: Immune globulin IV (Human-slra). Dose: 300–800 mg/kg every 3–4 weeks for primary humoral immunodeficiency. Purpose: Replacement therapy in patients with recurrent infections and poor antibody production, which may coexist with complement receptor issues. Side effects: Infusion-related symptoms, headache, nausea, rare thrombotic or kidney complications.

6. QIVIGY (IVIG)
Class: Immune globulin IV, 10% solution. Dose: Dosing schedules for adults with primary humoral immunodeficiency are similar (around 300–600 mg/kg every 3–4 weeks), adjusted to response. Purpose: Reduce serious and recurrent bacterial infections. Side effects: Similar to other IVIGs – infusion reactions, headache, risk of thrombosis and renal dysfunction in susceptible patients.

7. Amoxicillin (prophylactic or treatment antibiotic)
Class: Aminopenicillin antibacterial. Dose example: 250–500 mg orally every 8–12 hours in adults for many respiratory infections; prophylactic regimens are individualized and may use once- or twice-daily dosing. Purpose: Treat or prevent common respiratory and ear infections. Mechanism: Inhibits bacterial cell-wall synthesis of susceptible organisms. Side effects: Allergy, rash, diarrhea, candidiasis; rare severe allergic reactions.

8. Amoxicillin–clavulanate
Class: β-lactam/β-lactamase inhibitor. Dose example: 875/125 mg twice daily in adults for sinusitis or bronchitis; prophylactic doses are lower and individualized. Purpose: Broader coverage of β-lactamase–producing bacteria in sinuses, lungs and skin. Mechanism: Amoxicillin blocks cell-wall synthesis; clavulanate blocks many β-lactamases. Side effects: Gastrointestinal upset, diarrhea, liver-enzyme elevation, allergy.

9. Azithromycin (prophylactic macrolide)
Class: Macrolide antibiotic. Dose example: 250–500 mg once daily or three times weekly for prophylaxis in some chronic lung diseases; exact regimen is specialist-guided. Purpose: Reduce frequency of respiratory infections and provide some anti-inflammatory effect. Mechanism: Inhibits bacterial protein synthesis and modulates inflammatory pathways. Side effects: Nausea, diarrhea, QT-interval prolongation, rare liver injury.

10. Trimethoprim–sulfamethoxazole (cotrimoxazole)
Class: Folate-pathway–inhibiting antibiotic combination. Dose example: Once-daily low-dose prophylaxis or higher doses twice daily for treatment; exact schedule is tailored. Purpose: Prevent or treat bacterial respiratory, ear, sinus and some opportunistic infections. Mechanism: Sequential inhibition of bacterial folate synthesis. Side effects: Rash, photosensitivity, bone-marrow suppression, hyperkalaemia and rare severe skin reactions.

11. Oral cephalosporins (e.g., cefuroxime)
Class: Second-generation cephalosporin antibiotic. Dose example: 250–500 mg twice daily for respiratory infections. Purpose: Alternative or step-up therapy in patients with β-lactam–sensitive organisms or penicillin intolerance. Mechanism: Inhibits cell-wall synthesis. Side effects: Diarrhea, allergy, possible C. difficile infection.

12. Fluoroquinolones (e.g., levofloxacin) – specialist use only
Class: Fluoroquinolone antibiotic. Dose example: 500–750 mg once daily in adults for serious pneumonia; usually reserved for older teens/adults with resistant infections. Purpose: Broad coverage for severe respiratory or systemic infections when other choices are unsuitable. Mechanism: Inhibits bacterial DNA gyrase and topoisomerase. Side effects: Tendon injury, QT prolongation, CNS effects; careful risk–benefit assessment required.

13. Meningococcal conjugate vaccines (e.g., MenACWY)
Class: Conjugate vaccine (biologic “drug”). Dose: Age-dependent schedules with boosters, especially in complement pathway defects. Purpose: Protect against invasive meningococcal disease, which is more common when complement function is impaired. Mechanism: Induces specific anti-capsular antibodies that work together with remaining complement activity. Side effects: Local pain, mild fever, very rare allergic reactions.

14. Pneumococcal vaccines (PCV13/PCV15 and PPSV23)
Class: Conjugate and polysaccharide vaccines. Dose: Childhood schedule plus adult boosters and 23-valent polysaccharide vaccine at recommended intervals. Purpose: Reduce invasive pneumococcal disease and pneumonia. Mechanism: Induces opsonizing antibodies against multiple pneumococcal serotypes. Side effects: Local reactions, low-grade fever.

15. Haemophilus influenzae type b (Hib) and influenza vaccines
Class: Inactivated or conjugate vaccines. Dose: Routine schedule with yearly inactivated influenza vaccination. Purpose: Protect against Hib meningitis/pneumonia and seasonal influenza, both of which can be life-threatening in immunodeficient patients. Side effects: Local pain, mild fever, rare severe allergy.

16. Low-dose oral corticosteroids (for autoimmune complications)
Class: Glucocorticoid anti-inflammatory drug. Dose example: Prednisone often started at 0.25–0.5 mg/kg/day and then tapered, depending on disease. Purpose: Control autoimmune manifestations such as lupus-like disease or autoimmune cytopenias linked to complement receptor abnormalities. Mechanism: Broad suppression of inflammatory cytokines and immune cell activity. Side effects: Weight gain, high blood pressure, osteoporosis, infection risk.

17. Hydroxychloroquine (for lupus-like autoimmunity)
Class: Antimalarial with immunomodulatory effects. Dose example: About 5 mg/kg/day (up to 400 mg/day in adults), with eye monitoring. Purpose: Treat lupus-like rashes, arthritis and immune-complex disease that can appear in complement-related disorders. Mechanism: Alters lysosomal pH and toll-like receptor signaling, reducing autoantibody-driven inflammation. Side effects: Retinal toxicity with long-term use, GI upset, skin pigmentation.

18. Rituximab (for severe autoimmunity or lymphoid complications)
Class: Anti-CD20 monoclonal antibody. Dose example: 375 mg/m² weekly for 4 doses or disease-specific regimens in autoimmunity. Purpose: Deplete B cells in severe autoimmune disease or lymphoproliferation. Mechanism: Targets CD20 on B cells, reducing autoantibody production and immune-complex formation. Side effects: Infusion reactions, infections, rare progressive multifocal leukoencephalopathy (PML).

19. Antifungals (e.g., itraconazole) in selected high-risk patients
Class: Triazole antifungal. Dose example: Commonly 100–200 mg once or twice daily in adults for prophylaxis or treatment; regimen individualized. Purpose: Prevent invasive fungal infections in patients with severe neutrophil dysfunction, as used in other phagocytic defects such as chronic granulomatous disease. Mechanism: Inhibits fungal ergosterol synthesis. Side effects: Liver-enzyme elevation, drug interactions, photosensitivity.

20. Antiviral drugs (e.g., oseltamivir) during influenza exposure
Class: Neuraminidase inhibitor. Dose example: 75 mg twice daily for 5 days in adults for treatment; lower daily dose for prophylaxis in some guidelines. Purpose: Reduce severity and duration of influenza, which can trigger bacterial superinfection. Mechanism: Blocks influenza virus release from infected cells. Side effects: Nausea, vomiting, rare neuropsychiatric events.

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Dietary molecular supplements

These supplements do not fix the genetic receptor problem, but they may support overall immune health when used safely under medical advice.

1. Vitamin D
Vitamin D helps regulate both innate and adaptive immune responses. Many people with chronic illness are deficient. Typical adult supplement doses range from 600–2000 IU/day, adjusted based on blood levels. Vitamin D modulates T-cell function and antimicrobial peptide production, which may lower respiratory infection risk. Excess doses can cause high calcium levels and kidney problems, so monitoring is important.

2. Vitamin C
Vitamin C is a water-soluble antioxidant that supports barrier function and neutrophil activity. Supplemental doses of 200–1000 mg/day are commonly used. It helps protect cells from oxidative damage generated during infections and may slightly shorten the duration of common colds. High doses can cause stomach upset and kidney-stone risk in susceptible people.

3. Zinc
Zinc is essential for normal development of immune cells and antibody production. Typical supplemental doses are 10–20 mg elemental zinc per day; higher doses should be time-limited. Zinc deficiency increases infection risk, so correcting low zinc may reduce respiratory and diarrheal illnesses. Too much zinc can cause nausea and interfere with copper absorption, leading to anemia and nerve problems.

4. Selenium
Selenium is a trace mineral needed for antioxidant enzymes and normal immune signaling. Usual supplement doses are 50–100 micrograms daily. Adequate selenium helps T cells and antibody responses work efficiently. Chronic high intake, however, can cause hair loss, nail changes and nerve symptoms, so blood levels and total dietary intake should be considered.

5. Omega-3 fatty acids (fish-oil EPA/DHA)
Omega-3 fatty acids from fish oil (commonly 500–1000 mg/day of combined EPA/DHA) have anti-inflammatory properties. They are often used to support cardiovascular and joint health and may gently modulate chronic inflammation that can accompany autoimmune features of complement receptor disorders. Side effects include fishy aftertaste and, at high doses, a small increase in bleeding tendency.

6. Probiotics
Probiotics are live bacteria (such as Lactobacillus or Bifidobacterium) taken to support gut microbiota. Typical doses are billions of colony-forming units per day for weeks or months. They may reduce antibiotic-associated diarrhea and some respiratory infections, though evidence is variable. In severely immunocompromised patients, they must be used with caution because rare bloodstream infections have been reported.

7. Folate (folic acid)
Folate is needed for DNA synthesis in rapidly dividing cells, including bone-marrow cells that make white cells. Supplemental doses are usually 400–800 micrograms daily. Correcting folate deficiency helps support normal blood counts and immune function. Very high doses may mask vitamin B12 deficiency, so monitoring by a doctor is important.

8. Vitamin B12
Vitamin B12 deficiency can cause anemia and impaired immunity. Typical oral doses are 250–1000 micrograms daily or periodic injections if absorption is poor. Restoring normal B12 status helps support healthy red and white blood cell production and nervous-system function, which is important in chronically ill patients.

9. N-acetylcysteine (NAC)
NAC is a precursor of glutathione and also a mucolytic agent. Oral doses of 600–1200 mg/day are used in some chronic lung diseases to thin mucus and reduce oxidative stress. In patients with repeated chest infections and bronchiectasis, NAC may support mucus clearance together with physiotherapy. Side effects include nausea and rare allergic reactions.

10. Curcumin (from turmeric)
Curcumin is a plant polyphenol with anti-inflammatory and antioxidant properties. Typical supplemental doses are 500–1000 mg/day of standardized extract, often taken with black pepper (piperine) to improve absorption. It may help dampen low-grade inflammation and joint pain associated with autoimmune features, but evidence is still emerging. High doses can upset the stomach and interact with blood-thinners.

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Immune-boosting / regenerative / stem-cell–related drugs

These medicines are not routine for complement receptor deficiency but may be used in related primary immunodeficiencies or in the context of stem-cell transplantation. Use is highly specialist.

1. Filgrastim (G-CSF)
Filgrastim is a granulocyte colony-stimulating factor that increases neutrophil production. Typical doses are around 5 µg/kg/day subcutaneously for limited periods. In conditions with low neutrophil counts, raising neutrophils can reduce infection risk. It does not fix complement receptors but supports overall phagocyte numbers. Bone pain and high white-cell counts are common side effects.

2. Sargramostim (GM-CSF)
Sargramostim stimulates both neutrophil and monocyte production. Dosing schedules vary (for example 250 µg/m²/day). It may be used after bone-marrow transplant or chemotherapy to speed immune recovery. By increasing circulating phagocytes, it may indirectly help compensate for partial receptor dysfunction. Side effects include fever, bone pain and fluid retention.

3. Interferon-gamma-1b
Interferon-gamma is used in chronic granulomatous disease and sometimes other phagocyte defects to boost oxidative burst activity. Typical doses are given subcutaneously three times per week. It increases microbial killing by macrophages and neutrophils. Side effects include flu-like symptoms and injection-site reactions. Its role in pure complement receptor deficiency is uncertain and would be experimental.

4. Eltrombopag (thrombopoietin receptor agonist)
Eltrombopag stimulates platelet production. In some immune cytopenias or bone-marrow failure overlapping with immunodeficiency, it helps correct low platelet counts. Usual doses are 25–75 mg daily, adjusted to platelet response. It does not treat complement receptor defects directly but supports hematologic health. It can cause liver-enzyme elevation and risk of thrombosis.

5. Conditioning drugs for hematopoietic stem-cell transplantation (HSCT)
In severe CD18-related disease (leukocyte adhesion deficiency type I, which includes loss of CR3/CR4 function), HSCT can be curative. Conditioning regimens use drugs such as busulfan, cyclophosphamide or fludarabine to prepare the marrow for new stem cells. These drugs destroy existing marrow cells so transplanted healthy stem cells can engraft, but they have significant short- and long-term toxicities and are only used in specialist centers.

6. Experimental complement-receptor–targeted agents (e.g., CR3 agonists)
Small-molecule CR3 agonists like leukadherin-1 have been studied in models of vascular injury and inflammation. They increase CR3-mediated adhesion and phagocytosis in experimental systems. Their clinical use in human complement receptor deficiency is investigational only and not standard care.

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Surgical treatments

Surgery is supportive, not curative, and is used to manage damage from repeated infections or to deliver definitive HSCT.

1. Hematopoietic stem-cell transplantation (HSCT / bone-marrow transplant)
In severe CD18-related leukocyte adhesion deficiency, HSCT can replace the defective immune system with donor stem cells that express normal CR3/CR4 and LFA-1. This involves conditioning chemotherapy, infusion of donor stem cells and long monitoring. HSCT can be life-saving but carries risks such as graft-versus-host disease, infections and organ toxicity.

2. Central venous catheter placement
Some patients need frequent IV antibiotics or immunoglobulin infusions. A tunneled central line or implanted port can make repeated access easier and reduce trauma from many needle sticks. However, central lines themselves increase infection risk, so strict line-care protocols are critical.

3. Functional endoscopic sinus surgery (FESS)
If chronic sinusitis does not respond to medicines, ENT surgeons may perform FESS to open and drain blocked sinuses. In a patient with complement receptor deficiency and constant sinus infections, this can reduce the number of infections and improve quality of life, but careful peri-operative antibiotics are needed.

4. Ventilation tubes for recurrent otitis media
Children or adults with frequent middle-ear infections may receive tympanostomy tubes (grommets) to ventilate the middle ear and reduce fluid buildup. This decreases the frequency of painful infections and helps protect hearing, which is important in people already burdened by systemic illness.

5. Resection of severely damaged lung segments
In rare cases with advanced bronchiectasis localized to a small lung region, surgeons may remove the most destroyed segment or lobe. This can decrease chronic infection and bleeding, but it is major surgery and chosen only when medical therapy fails.

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Prevention strategies

1. Keep all routine and special vaccines up to date for both patient and close contacts.

2. Follow an agreed early-fever plan with rapid access to medical care and antibiotics.

3. Practice strict hand hygiene and respiratory etiquette, especially in schools, workplaces and public transport.

4. Avoid smoking, second-hand smoke and heavily polluted environments as much as possible.

5. Attend regular immunology and lung follow-up appointments even when feeling well.

6. Treat sinus, dental and skin infections promptly before they spread or become chronic.

7. Maintain good nutrition, hydration, sleep and stress management to support general immune function.

8. Use prophylactic antibiotics or Ig replacement only exactly as prescribed; do not stop early when feeling better.

9. Carry an emergency information card or bracelet that mentions the immunodeficiency and preferred antibiotics.

10. For families, pursue genetic counseling to understand risks for future children and to detect affected relatives early.

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When to see a doctor

People with complement receptor deficiency should have regular planned visits with an immunologist, but there are also urgent situations. Seek medical help immediately (emergency department if needed) for fever, chills, fast or difficult breathing, severe headache, neck stiffness, new rash with purple spots, confusion, very bad sore throat, chest pain, or rapidly spreading skin redness. These signs may indicate meningitis, sepsis or pneumonia, which can progress more quickly because phagocytes cannot grab complement-coated bacteria efficiently.

Routine follow-up is also needed if infections are becoming more frequent again, if there is new weight loss, night sweats, prolonged diarrhea, unexplained bruising or signs of autoimmune disease (joint swelling, mouth ulcers, sun-sensitive rash). Early review allows doctors to adjust IgG dose, prophylactic antibiotics or investigate for complications such as bronchiectasis or autoimmune disease.

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Diet – what to eat and what to avoid

1. Eat plenty of fruits and vegetables rich in vitamins, minerals and antioxidants (like citrus, berries, leafy greens, carrots) to support general immunity.

2. Include lean protein (fish, poultry, eggs, legumes) at each meal to support antibody and immune-cell production.

3. Choose whole grains (brown rice, oats, whole-wheat bread) instead of refined grains to stabilize energy and support gut health.

4. Use healthy fats from nuts, seeds, olive oil and oily fish for anti-inflammatory omega-3s.

5. Stay well-hydrated with safe drinking water; dehydration can worsen fatigue and mucus thickness.

6. Limit ultra-processed foods high in sugar, salt and trans fats, which promote inflammation and weight gain.

7. Avoid raw or undercooked animal products (raw eggs, undercooked meat, unpasteurized milk) to reduce food-borne infections.

8. Be careful with salad bars and street foods where hygiene is uncertain, especially when traveling.

9. Limit alcohol (if used at all) because it can impair immunity and interact with many medicines.

10. Discuss any supplements or restrictive diets with your doctor or dietitian to avoid nutrient gaps or dangerous interactions with prescribed drugs.

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Frequently asked questions (FAQs)

1. Is complement receptor deficiency the same as complement component deficiency?
No. Complement component deficiencies involve missing or defective complement proteins like C2 or C3 in the blood. Complement receptor deficiency means the receptors on cell surfaces that bind complement-coated particles are abnormal or absent. Both can cause recurrent infections and autoimmune disease, but lab tests and genetic findings are different, and management is individualized.

2. How is complement receptor deficiency diagnosed?
Doctors usually suspect the condition in people with repeated infections, poor wound healing or severe gum disease. Tests may include complement levels and function, flow cytometry to check expression of CD18, CR3, CR4 or CD21 on white cells or B cells, and genetic testing of genes like ITGB2 (CD18) or CR2. The diagnosis should be made in a specialist immunology center.

3. Can complement receptor deficiency be cured?
Most forms cannot be corrected by simple medicines. However, in severe CD18-related leukocyte adhesion deficiency, allogeneic stem-cell transplantation (HSCT) or emerging gene-therapy approaches can be curative by providing stem cells that express normal receptors. For other receptor defects, treatment usually focuses on lifelong infection prevention and management of complications.

4. Will I always need antibiotics?
Not everyone needs daily prophylactic antibiotics. Some patients only need early, aggressive treatment of infections, while others with very frequent or severe infections may receive continuous low-dose prophylaxis. Decisions are based on infection history, lung imaging, IgG levels and response to vaccines, and are regularly reviewed to avoid resistance.

5. Do all patients require immunoglobulin (IVIG) replacement?
No. IVIG is usually considered when there is proven antibody deficiency (low IgG or poor vaccine responses) in addition to complement receptor problems. If antibody production is normal and infections are mild, IVIG may not be needed. When used, doses are adjusted to minimize infections while limiting side effects and cost.

6. Is it safe to receive live vaccines?
In many complement-related disorders, the main problem is with bacterial clearance, not severe T-cell defects, so several live vaccines may still be safe. However, decisions about live vaccines (such as MMR or varicella) depend on the full immune evaluation, coexisting conditions and local guidelines, and must be made by the immunologist.

7. Will I pass this condition to my children?
Many complement receptor defects are inherited in an autosomal recessive way, meaning both parents carry one abnormal copy. Each child then has a 25% chance of being affected. Genetic counseling and, when appropriate, carrier or prenatal testing can help families understand risks and options.

8. Why do some patients also develop autoimmune diseases?
Complement receptors help clear immune complexes and dying cells. When this clearance is inefficient, immune complexes can deposit in tissues and trigger autoimmune reactions like lupus-like disease or autoimmune hemolytic anemia. So the same defect that causes infections may also disturb self-tolerance and cause autoimmunity.

9. Can lifestyle changes really make a difference?
Yes. While lifestyle changes cannot fix the genetic problem, good hygiene, smoking avoidance, healthy sleep, exercise and nutrition reduce the burden of infections and speed recovery. These measures work together with medical treatments like vaccines, antibiotics and IVIG.

10. Are there special precautions before surgery or dental work?
Before any invasive procedure, doctors and dentists need to know about the immunodeficiency. They may prescribe prophylactic antibiotics and plan close monitoring afterward. Good pre- and post-operative infection control is especially important because complement receptor defects impair phagocyte function and wound defense.

11. Can I go to school or work normally?
Most people can attend school or work with reasonable precautions, such as avoiding close contact with people who have obvious infections, staying home when ill, and following vaccination recommendations. An individualized letter from the immunologist can help schools or employers understand needed accommodations.

12. What is the long-term outlook (prognosis)?
Prognosis depends on the specific gene defect, severity of receptor loss, age at diagnosis and access to specialized care. With early recognition, good infection prevention, appropriate use of IVIG and antibiotics, and treatment of complications, many patients can live into adulthood with improved quality of life. Severe untreated cases, especially LAD I, have higher risks of life-threatening infections.

13. Is gene therapy available now?
Gene therapy is an active research field for several primary immunodeficiencies, including some forms of leukocyte adhesion deficiency. Early trials show that inserting a normal copy of the defective gene into stem cells can restore function, but such therapies are still limited to research centers and are not yet widely available or standard for complement receptor deficiency.

14. Can complementary or herbal remedies replace medical treatment?
No. Herbal products and complementary therapies cannot replace vaccines, antibiotics, IVIG or other proven treatments. Some herbs can interact with prescribed medicines or suppress immunity further. Any complementary therapy should be discussed with the medical team to check for safety and interactions.

15. What should I do if I feel overwhelmed by my diagnosis?
Feeling worried or overwhelmed is completely understandable. Talking with your immunologist, a psychologist, family and patient-support groups can help. Many people find it easier to cope when they understand their condition, have a clear plan for infections and know they are followed by a specialist team experienced with rare immune disorders.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: February 26, 2025.