Common Variable Immunodeficiency-8 with Autoimmunity

Other names
How LRBA and the immune system work
Types (clinical patterns)
Causes and risk factors
Common symptoms and signs
Diagnostic tests
Non-pharmacological treatments (therapies and other measures)
Drug treatments
Dietary molecular supplements
Immunity-booster, regenerative, and stem-cell-related therapies
Surgeries and major procedures
Prevention and long-term protection
When to see doctors urgently
What to eat and what to avoid
Frequently asked questions

Common variable immunodeficiency-8 with autoimmunity is a rare inherited immune system disease caused by harmful changes in the LRBA (lipopolysaccharide-responsive beige-like anchor) gene. This gene helps immune regulatory proteins, especially CTLA-4, stay inside immune cells and work properly. When LRBA does not work, CTLA-4 is broken down too quickly, so “brakes” on the immune system are lost. The result is a double problem: the body does not make enough good antibodies (like a weak defense army), and at the same time immune cells may attack the person’s own blood cells, gut, or other organs (autoimmunity). Children often show recurrent chest and sinus infections, diarrhea, enlarged spleen or lymph nodes, and autoimmune problems such as low platelets or anemia. [1]

Common variable immunodeficiency 8 with autoimmunity (often called CVID8) is a rare inherited disease of the immune system. It happens when both copies of a gene called LRBA are changed (mutated), so the body cannot make a normal LRBA protein. This protein helps immune cells work properly and stay under control.1

Because LRBA protein does not work, people with this condition have weak defense against germs and also too much immune attack against their own body, which is called autoimmunity. Children usually start to have problems early in life, such as repeated chest infections, long-lasting diarrhea, and diseases where the immune system destroys blood cells or inflames the gut.1 2

In many patients, CVID-8 looks like classic common variable immunodeficiency (CVID) but with stronger autoimmune and inflammatory signs. Autoimmune cytopenias (immune thrombocytopenic purpura, autoimmune hemolytic anemia, neutropenia), inflammatory bowel disease-like colitis, and lung inflammation are frequent complications. [2] These problems can be long-lasting and may damage organs such as lungs (bronchiectasis), liver, and gut if they are not treated early and continuously. [3]

Because this is a complex, life-long condition, treatment is usually managed by a specialist immunology / hematology team in a hospital. The main goals are to reduce infections, control autoimmunity, protect organs, and give the child or adult as normal a life as possible. Therapies combine careful daily care, non-drug measures, medicines, and sometimes advanced procedures like stem cell transplantation in very severe cases. [3][4]

Doctors call it “common variable” because blood tests show low antibody levels like classic CVID, but the genetic cause is a specific LRBA mutation, so it is listed separately as type 8. It is passed in an autosomal recessive way, which means both parents usually carry one faulty copy but are healthy themselves.2 3

Other names

This disease can appear under several related names in medical books and databases. All of them point to the same or closely related condition caused by LRBA gene problems.1 2

Common variable immunodeficiency-8 with autoimmunity (CVID8) – Official name used in disease ontologies and genetic databases.2
Combined immunodeficiency due to LRBA deficiency – Stresses that both arms of the immune system (antibody and cell-mediated) can be affected.1 5
LRBA deficiency with autoimmunity – Focuses on the main gene (LRBA = lipopolysaccharide-responsive beige-like anchor protein) and the autoimmune features.4
Immune checkpoint deficiency due to LRBA mutation – Used in some reviews because LRBA helps protect a control protein called CTLA-4, which calms T cells.6

How LRBA and the immune system work

The LRBA protein is made inside immune cells, especially B cells and some T cells. It helps move tiny sacs (vesicles) inside the cell so that important proteins, like CTLA-4, can be sent to the right place and not destroyed too early. CTLA-4 is a “brake” that helps stop T cells from over-reacting.4 7

When LRBA is missing or very low, CTLA-4 is broken down faster, so there is less brake on the immune system. T cells can then stay active for too long and attack the body’s own cells, causing autoimmunity. At the same time, B cells have trouble maturing and making normal antibodies (immunoglobulins), so infections become more frequent.4 8

Research shows that LRBA mutations disturb B-cell activation, antibody secretion, and cell survival (autophagy and apoptosis), leading to low immunoglobulin levels (hypogammaglobulinemia) and poor vaccine responses. This combination of weak defense and self-attack explains why CVID8 patients have both infections and autoimmune illnesses.4 9

Types (clinical patterns)

All known patients share LRBA gene problems, but the clinical picture can look different from person to person. Doctors sometimes think about practical “types” based on the main problems, not on different genes.5 10

Infection-dominant type – Some patients mainly show repeated infections, such as ear infections, sinusitis, and pneumonia, with less obvious autoimmunity early on.1 11
Autoimmunity-dominant type – Other patients show strong autoimmune problems (like low platelets or anemia) as the first or main feature, even before serious infections are noticed.6 8
Gut-dominant type – Some children mainly have chronic diarrhea, poor weight gain, or inflammatory bowel disease–like colitis due to ongoing immune attack in the intestines.1 7
Lymphoproliferative / organ-enlargement type – A few patients show large lymph nodes, big spleen, and sometimes lung damage or nodules, reflecting chronic immune stimulation.6 12

These patterns often overlap in the same person and can change over time, so they are just a simple way to think about the disease, not strict separate categories.5 11

Causes and risk factors

Here “causes” mainly means the true genetic cause plus other factors that can influence how severe the disease becomes or when it shows up.

Homozygous LRBA gene mutation (main cause)
The key cause is a harmful change in both copies of the LRBA gene on chromosome 4. This change makes LRBA protein absent or very low, which leads directly to CVID8.2 4
Autosomal recessive inheritance from carrier parents
Most affected children inherit one faulty LRBA gene from each parent, who usually have no symptoms. When two carriers have a child, there is a 25% chance in each pregnancy that the child will have the disease.2 3
Consanguinity (parents related by blood)
In some reports, affected children come from families where parents are cousins or otherwise related. This makes it more likely that both parents carry the same rare LRBA mutation.4 10
Defective CTLA-4 “brake” pathway
LRBA helps protect CTLA-4 from being destroyed. Without LRBA, CTLA-4 levels fall, and T cells lose an important brake, causing immune over-activity and autoimmunity.6 1
Abnormal B-cell development and class switching
LRBA mutations disturb B-cell activation, formation of plasma cells, and switching from IgM to other antibody types. This leads to low IgG and IgA and poor vaccine responses.4 9
Problems with autophagy in immune cells
Research shows LRBA deficiency affects autophagy, the “self-cleaning” process of cells. Poor autophagy can damage immune cell survival and function, adding to immune weakness and mis-control.4 16
Increased apoptosis (cell death) of lymphocytes
LRBA-mutated lymphocytes can die more easily, reducing helpful immune cells and contributing to low antibody production and infections.4 9
Imbalance of regulatory T cells (Tregs)
Many CVID and LRBA-deficient patients have lower or poorly working regulatory T cells, which normally prevent autoimmunity. This imbalance allows autoimmune attacks on blood cells, gut, joints, or other organs.6 8
Chronic immune activation and inflammation
Repeated infections and ongoing autoimmunity keep the immune system “switched on” all the time, causing enlarged lymph nodes, big spleen, and tissue damage over the years.5 6
Other immune genes that modify severity
Some patients may have additional changes in other immune regulation genes (for example in the CTLA-4 pathway) that can make symptoms more severe or different, even with the same LRBA mutation.6 8
Early-life viral or bacterial infections as triggers
Serious infections in early childhood can reveal the underlying LRBA defect because the immune system cannot clear germs properly, leading to pneumonia, sepsis, or gut infections.1 11
Imbalance of gut microbiome
Ongoing diarrhea and gut inflammation in LRBA deficiency may be linked to disturbed gut bacteria, which can further stimulate the immune system and worsen autoimmunity in the intestine.7 8
Family history of primary immunodeficiency or autoimmunity
Children from families with many cases of early infections, immune weakness, or autoimmune disease are more likely to carry shared genetic risks, including LRBA mutations.5 11
Environmental infections that provoke autoimmunity
Some infections may indirectly trigger autoimmune features in genetically susceptible people, adding to the autoimmunity seen in LRBA deficiency.6 8
Delayed diagnosis and treatment
If LRBA deficiency is not recognized for many years, repeated infections and uncontrolled autoimmunity can cause permanent damage to lungs, gut, or blood cells, making the disease appear worse.1 12
Inadequate vaccination responses
Because antibody responses to vaccines are weak, patients stay vulnerable to vaccine-preventable infections, which then add to the overall disease burden.9 11
Coexisting allergic or atopic disease
Some LRBA-deficient patients have eczema, asthma, or other atopic problems, which reflect general immune imbalance and may worsen quality of life.6 12
Coexisting autoimmune endocrine or rheumatic disease
Thyroid disease, arthritis, or diabetes can appear with LRBA deficiency, adding extra autoimmunity “layers” to the main immune defect.7 17
Gender and hormonal influences (possible)
Some immune diseases show sex differences, though data for LRBA deficiency are still limited. Hormones may change immune responses, but this is still being studied.6 11
Unknown or not yet discovered modifiers
Scientists think there are still other genes and environmental factors that affect who becomes sick and how severe CVID8 becomes, but these are not fully known yet.4 6

Common symptoms and signs

Repeated ear, sinus, and chest infections
Children often have many episodes of ear infections, sinusitis, bronchitis, or pneumonia each year because their antibody levels are low and germs are not cleared well.1 11
Chronic cough and breathing problems
A long-lasting cough, wheeze, or breathlessness can appear. Over time, repeated infections may damage airways and cause bronchiectasis (permanent widening of the bronchi).5 11
Persistent or bloody diarrhea
Many patients have chronic diarrhea, sometimes with blood or mucus, due to immune-mediated inflammation of the gut that can resemble inflammatory bowel disease.1 7
Poor weight gain and growth (failure to thrive)
Because of infections and gut problems, children may not gain weight well, grow more slowly, and look smaller than peers.7 10
Long-lasting fatigue and low energy
Constant infections, anemia, and inflammation can make patients feel tired most of the time, with low school or work stamina.8 12
Enlarged lymph nodes
Glands in the neck, underarms, or groin can become large and sometimes tender, reflecting chronic immune activation.6 12
Enlarged spleen and sometimes liver
The spleen (and sometimes liver) may be enlarged. This can trap blood cells and worsen anemia or low platelets, and it is a sign of ongoing immune or blood cell problems.5 6
Autoimmune low platelets (immune thrombocytopenia)
The immune system may destroy platelets, causing easy bruising, nosebleeds, or bleeding gums due to immune thrombocytopenic purpura.1 8
Autoimmune hemolytic anemia
The immune system can attack red blood cells, causing pale skin, tiredness, yellow eyes (jaundice), and dark urine in autoimmune hemolytic anemia.1 6
Inflammatory bowel disease–like colitis
Some patients have severe gut pain, diarrhea, and weight loss due to autoimmune inflammation in the colon, looking similar to Crohn’s disease or ulcerative colitis.7 16
Chronic or recurrent arthritis
Joint pain, swelling, and stiffness (especially in knees, ankles, or hands) can come from autoimmune arthritis, sometimes similar to juvenile idiopathic arthritis.17 6
Skin rashes or autoimmune skin disease
Eczema-like rashes, urticaria (hives), or autoimmune skin conditions such as vitiligo can appear due to ongoing immune dysregulation.6 12
Frequent fevers without clear cause
Low-grade or repeated fever may reflect chronic inflammation or infection that is not fully controlled because of the immune defect.5 11
Autoimmune endocrine problems (for example thyroid)
Some patients develop autoimmune thyroid disease or other hormone gland problems, which can cause tiredness, weight change, or cold intolerance.6 17
Increased risk of lymphoma or other cancers (long-term)
Long-lasting immune activation and poor surveillance can raise the risk of certain cancers, especially lymphomas, in some CVID-like and LRBA-deficient patients, so long-term follow-up is important.6 11

Diagnostic tests

(Physical exam, manual tests, lab/pathological, electrodiagnostic, and imaging)

Full general physical examination (physical exam)
The doctor checks overall appearance, temperature, breathing, heart rate, and blood pressure, and looks for signs of infection, pallor, bruising, or rash. This simple step guides which deeper tests are needed.11 12
Growth and nutrition assessment (physical / manual)
Weight, height, head size, and body mass index are plotted on a growth chart. Poor growth or weight loss supports the idea of chronic infection or gut disease.10 11
Lymph node and spleen palpation (physical exam)
The doctor gently feels the neck, armpits, groin, and abdomen for enlarged lymph nodes, liver, or spleen. Organ enlargement is common in LRBA deficiency and suggests ongoing immune activation.5 6
Chest and lung examination with stethoscope (physical exam)
Listening to the lungs can reveal crackles, wheezes, or reduced breath sounds, which may point to pneumonia or chronic lung damage like bronchiectasis.11
Joint movement and swelling check (manual exam)
The doctor moves joints through their range and presses gently for swelling or warmth. Persistent arthritis can suggest autoimmune involvement in LRBA deficiency.17 6
Simple lung function test (peak flow) (manual with device)
A child blows into a small peak-flow meter. Low or variable readings may show airway obstruction or asthma-like involvement in addition to infections.11
Bedside stool occult blood card test (manual / bedside)
A small sample of stool is placed on a test card to check for hidden blood, which suggests gut inflammation or colitis in patients with diarrhea.7
Complete blood count (CBC) with differential (lab test)
This blood test measures red cells, white cells, and platelets. It can show anemia, low platelets, low neutrophils, or abnormal lymphocytes, which fit with immune deficiency and autoimmunity.9 8
Serum immunoglobulin levels (IgG, IgA, IgM) (lab test)
Measuring antibody levels is central. Many patients have low IgG and often low IgA or IgM, confirming a CVID-like antibody deficiency picture.11 9
Lymphocyte subset counts by flow cytometry (lab test)
This test counts T cells, B cells, and NK cells. Patterns such as low switched memory B cells or abnormal T-cell subsets are common in CVID and LRBA deficiency.9 6
Detailed B-cell phenotyping (switched memory B cells) (lab test)
More advanced flow cytometry looks at class-switched memory B cells, which are often reduced in LRBA deficiency, helping to distinguish it from some other immune defects.9 8
Vaccine antibody response test (lab test)
After certain vaccines, doctors can measure antibody levels to see if the body responded well. Poor response supports the diagnosis of an antibody deficiency like CVID8.11
Direct antiglobulin (Coombs) test (lab / autoimmune)
This blood test detects antibodies stuck to red blood cells. A positive result supports autoimmune hemolytic anemia, which is a common autoimmune feature in LRBA deficiency.1 8
Autoantibody profiles (ANA and others) (lab / autoimmune)
Tests such as ANA (antinuclear antibody) and other autoantibodies can show broad autoimmunity. These results help document the immune dysregulation component of CVID8.6 8
Stool cultures and inflammatory markers (lab / pathology)
Stool samples may be checked for germs and for markers like calprotectin that indicate gut inflammation. This helps separate infection from autoimmune enteropathy.7
Pulmonary function tests with spirometry (electrodiagnostic)
In a lung lab, the patient breathes into a machine that measures airflow and lung volumes. Abnormal patterns can show airway narrowing or restrictive damage from repeated infections.11
Electrocardiogram (ECG) when needed (electrodiagnostic)
An ECG checks the heart’s rhythm and electrical activity. It may be used if certain medicines or complications might affect the heart in patients with chronic systemic disease.11
Chest X-ray (imaging test)
A chest X-ray can show pneumonia, enlarged lymph nodes in the chest, or early signs of chronic lung damage. It is usually one of the first imaging studies done.11
High-resolution CT scan of the chest (imaging test)
CT scans give a much more detailed picture of the lungs, showing bronchiectasis, nodules, or interstitial changes often seen in CVID-like disorders.11 6
Abdominal ultrasound or CT scan (imaging test)
Imaging of the abdomen can show enlarged liver or spleen, swollen gut loops, or lymph nodes in the belly, all of which support the picture of immune dysregulation in LRBA deficiency.5 10

Non-pharmacological treatments (therapies and other measures)

1. Infection-prevention lifestyle program
A simple but powerful treatment is a daily infection-prevention routine: regular hand-washing, mask use during outbreaks, avoiding contact with people who have active flu, measles, chickenpox, or stomach viruses, and good ventilation at home and school. For a child or adult with CVID-8, this reduces exposure to germs that the weak immune system cannot handle well. The purpose is to lower infection frequency and protect lungs and ears from repeated damage. The mechanism is purely physical and behavioral: fewer germs reach the nose, throat, and lungs, so immune defenses are less overwhelmed. [6]

2. Vaccination plan for close contacts and selected non-live vaccines
People with CVID-8 often respond poorly to vaccines themselves, especially live vaccines which may be unsafe. However, vaccinating family members and classmates against flu, COVID-19, measles, and other infections builds a “ring of protection” around the patient. In some cases, patients may receive non-live vaccines (like inactivated influenza) after discussion with their specialist, mainly to reduce severity rather than guarantee full protection. The purpose is “herd protection” in the home, and the mechanism is that vaccinated contacts are less likely to bring infections into the house. [7]

3. Chest physiotherapy and airway clearance
Many people with LRBA-related CVID develop chronic lung problems such as bronchiectasis from repeated chest infections. Daily airway-clearance techniques (postural drainage, breathing exercises, oscillating devices) help loosen and remove mucus from the lungs. This reduces the number of bacteria sitting in the airways and can lower the risk of flare-ups and hospital admissions. The mechanism is mechanical cleaning of the bronchial tree, which improves oxygen exchange and reduces chronic inflammation. [8]

4. Nutritional optimization and growth support
Chronic diarrhea, malabsorption, and inflammatory bowel disease-like colitis are common in LRBA deficiency and CVID-8, so dietitian-guided nutrition is critical. The aim is to maintain healthy weight, muscle mass, and micronutrient levels (iron, vitamin D, B12, folate, zinc). This may include high-calorie oral supplements or, rarely, tube feeding during severe flares. Better nutrition improves immune cell function and helps the body cope with infections and autoimmune inflammation. [9]

5. Psychological and family support counseling
Living with a rare, chronic immune disease can be emotionally stressful for the patient and the entire family. Psychological support, support groups, and school counseling help children cope with hospital visits, isolation during infection outbreaks, and worries about the future. For parents, counseling provides tools to manage fear, burnout, and complex medical decisions. Better mental health is linked to better adherence to treatment and improved quality of life. [10]

6. Regular dental and ENT care
Patients with CVID-8 often have repeated sinus and ear infections. Regular review by ear-nose-throat and dental specialists helps detect chronic sinus disease, ear fluid, or dental infections early. Simple measures such as nasal saline irrigation, treatment of dental caries, and early antibiotics for bacterial sinusitis can prevent serious complications and hospital admissions. The mechanism is early local control of infection sources before they spread to lungs or bloodstream. [11]

7. Exercise and pulmonary rehabilitation
Tailored, gentle physical activity, sometimes guided by physiotherapists, helps keep lungs, heart, and muscles strong. For people with chronic lung disease or fatigue, structured pulmonary rehab programs teach paced breathing, endurance building, and safe exercise levels. This improves exercise tolerance, reduces shortness of breath, and enhances overall resilience against infections. [12]

8. Sunlight exposure and vitamin D–friendly lifestyle
Limited but regular safe sunlight exposure and outdoor activity can support vitamin D levels, which may help immune regulation and bone health—important in children on long-term steroids or with malabsorption. The purpose is to complement dietary vitamin D and reduce osteopenia or fractures. Mechanistically, ultraviolet light in small doses stimulates skin production of vitamin D, later activated in liver and kidneys. [13]

9. Infection-control education at school or workplace
Teachers and employers need clear written information about the patient’s condition. Simple steps like letting the person sit near a window, avoiding overcrowded rooms, allowing mask use, and giving rapid permission for medical appointments can dramatically cut infection risk and stress. The mechanism is environmental and social adaptation, reducing exposure to viruses and bacteria. [14]

10. Avoidance of smoking and indoor air pollutants
Smoking (active or passive), biomass fuel smoke, and air pollution worsen chronic lung disease and increase the risk of pneumonia. In CVID-8, where lungs are already vulnerable, strict avoidance is a crucial non-drug treatment. Cleaner air lowers airway inflammation, preserves lung function, and decreases exacerbations. [15]

Drug treatments

Because this is a rare disease, medicines are often used “off-label” but based on strong scientific reasoning. Always follow specialist advice and the official prescribing information for each drug. [16]

1. Immunoglobulin replacement therapy (IVIG and SCIG)
The main cornerstone treatment in CVID-8 is regular immunoglobulin G (IgG) replacement, given intravenously (IVIG) or under the skin (SCIG). FDA-approved immune globulin products for primary immunodeficiency (such as the IVIG preparations listed by the FDA and brands like Privigen and Gammagard) supply pooled antibodies from healthy donors to compensate for the patient’s low or poor-quality antibodies. [1] The purpose is to reduce frequency and severity of infections and to protect lungs and other organs. Mechanistically, IgG binds bacteria and viruses, helps immune cells clear them, and may also calm autoimmune inflammation. Dose and interval are individualized by weight, infection history, and trough IgG levels, using label guidance and specialist judgment. [17]

2. Prophylactic antibiotics
Many guidelines recommend long-term low-dose antibiotics, especially macrolides such as azithromycin, for patients who still get repeated lung infections despite good IgG replacement. The purpose is to prevent bacterial growth in the airways and to reduce exacerbations. Macrolides also have anti-inflammatory effects in the lung tissue. Exact choice, dose, and frequency (for example, several days per week) are chosen by the specialist based on age, kidney and liver function, and resistance patterns. [18]

3. Short-term systemic corticosteroids
Drugs like prednisone are often the first choice when autoimmune cytopenias (such as immune thrombocytopenia or autoimmune hemolytic anemia) flare. Steroids calm the overactive immune cells that are destroying blood cells and reduce inflammatory chemicals. They are very effective in the short term, but long-term use can cause serious side effects such as weight gain, high blood pressure, diabetes, osteoporosis, mood changes, and infection risk. Doctors try to use the lowest effective dose for the shortest time, then switch to more targeted agents. [19]

4. Rituximab (CD20-targeted monoclonal antibody)
Rituximab is a monoclonal antibody that targets CD20 on B cells and is FDA-approved for lymphomas, rheumatoid arthritis, and some autoimmune diseases. [2] In CVID with autoimmune cytopenias or granulomatous-lymphocytic interstitial lung disease (GLILD), rituximab is widely used off-label when steroids and simpler drugs are not enough. [3] It works by depleting B cells that produce autoantibodies and drive inflammation. Studies and reviews show rituximab can effectively control autoimmune cytopenias and GLILD in many CVID patients, but it can also worsen low IgG levels and increase infection risk, so it is usually used together with IgG replacement and close monitoring. Serious potential side effects include infusion reactions, infections, rare brain infection (PML), and reactivation of hepatitis B, as highlighted in FDA prescribing information for rituximab and its biosimilars. [4] [20]

5. Azathioprine and other conventional immunosuppressants
Agents such as azathioprine, mycophenolate mofetil, or methotrexate may be used as steroid-sparing drugs for chronic autoimmune cytopenias, gut inflammation, or arthritis-like symptoms. They work by slowing down rapidly dividing immune cells, especially T and B lymphocytes, lowering the attack on the person’s own tissues. Their purpose is long-term stabilization with less steroid exposure. Side effects can include bone-marrow suppression (low blood counts), liver enzyme changes, nausea, and increased infection risk, so regular blood tests are essential. [21]

6. Abatacept (CTLA4-Ig fusion protein – targeted therapy for LRBA deficiency)
Because LRBA deficiency leads to defective CTLA-4 “brakes” on T cells, abatacept, a CTLA-4–immunoglobulin fusion protein, is a rational targeted drug. Clinical studies in LRBA deficiency patients show that abatacept can significantly improve lymphoproliferation (enlarged lymph nodes and spleen), inflammatory bowel disease, and autoimmune cytopenias, and can reduce disease activity scores. [5] The mechanism is that abatacept acts as an artificial CTLA-4, binding co-stimulatory molecules on antigen-presenting cells and turning down T-cell activation. Side effects include increased risk of infections, infusion or injection reactions, and possible reactivation of latent infections. Dose and schedule follow approved indications for other autoimmune diseases and are carefully adapted for LRBA deficiency by experts. [22]

7. Sirolimus and other mTOR or targeted pathway inhibitors
Some LRBA-deficient patients benefit from sirolimus, an mTOR inhibitor, especially when there is lymphoproliferation or autoimmune cytopenias that do not respond to simple treatment. These drugs interfere with T-cell activation and proliferation through the mTOR pathway. They can help shrink enlarged lymph nodes and spleen and improve cytopenias. Side effects may include high cholesterol, mouth ulcers, delayed wound healing, and infection risk, and require blood-level monitoring. [23]

8. Biologic agents for specific autoimmune problems
Depending on the organ involved, doctors may use other biologic agents commonly used for autoimmune diseases, such as anti-TNF drugs or other targeted biologics, especially for inflammatory bowel disease-like colitis or arthritis. These are chosen case by case after weighing infection risk, as CVID-8 patients already have immune weakness. Mechanisms depend on the molecule (blocking TNF, IL-12/23, or other pathways), aiming to calm organ-specific inflammation while maintaining as much host defense as possible. [24]

9. Supportive drugs for complications (bronchodilators, proton-pump inhibitors, etc.)
Many patients need medicines to control complications: bronchodilators and inhaled steroids for chronic lung disease, proton-pump inhibitors for gastritis or reflux, and pain control medicines for arthritis. These drugs do not correct the core immune defect but improve daily comfort and function, which is an important part of long-term care. [25]

10. Emergency antibiotics and hospital-based treatments
Because infections can progress quickly in CVID-8, doctors often give patients and families a clear emergency plan, sometimes including oral “rescue” antibiotics to start at the first warning signs, followed by urgent review. Severe infections may need IV antibiotics and hospital care. The purpose is to shorten the time between first symptom and effective treatment, reducing the chance of sepsis or permanent lung damage. [26]

(Many more conventional and targeted drugs can be used in special situations. They all require specialist supervision and reference to the official FDA or regional prescribing information.)

Dietary molecular supplements

Supplements should never replace core treatments like immunoglobulin therapy. They are supportive and must be checked with the treating team to avoid interactions. [27]

1. Vitamin D
Vitamin D is important for bone health and also supports balanced immune function. In CVID-8, low vitamin D is common due to limited sun exposure, steroid use, and gut problems. Supplementation at an age- and weight-appropriate dose chosen by the doctor can help keep bones strong and may slightly improve immune regulation. Mechanistically, vitamin D receptors on immune cells influence T-cell and B-cell behavior and reduce over-inflammation. [28]

2. Calcium with vitamin D for bone protection
Children and adults on long-term steroids or with chronic inflammation have increased risk of osteoporosis. Combined calcium and vitamin D supplements (with doses based on dietary intake and lab tests) support bone mineralization. Calcium is the building block of bone, while vitamin D helps the gut absorb calcium and helps bone cells remodel correctly. This reduces fracture risk and improves growth. [29]

3. Iron (when iron-deficiency anemia is present)
Chronic blood loss from autoimmune hemolytic anemia or gut inflammation can cause iron deficiency. Oral or IV iron, when prescribed after confirming low iron stores, improves red blood cell production and energy levels. The mechanism is simple: iron is necessary to build hemoglobin, the oxygen-carrying molecule in red cells. Restoring iron stores supports recovery from anemia but must be combined with control of underlying autoimmunity. [30]

4. Vitamin B12 and folate
Autoimmune gastritis, small-bowel disease, or long-term medications can cause low vitamin B12 or folate levels, leading to anemia and neurological symptoms. Supplementation, by mouth or injection as advised, helps normalize DNA synthesis in bone marrow cells and protects nerves. In CVID-8, correcting these deficiencies supports better blood counts and energy. [31]

5. Zinc
Zinc plays a role in normal development and function of immune cells. Some people with chronic diarrhea or reduced intake may have low zinc. Carefully dosed supplements, monitored by the care team, can support wound healing and immune competence, though high doses can disturb copper balance, so monitoring is essential. [32]

6. Omega-3 fatty acids (fish-oil based)
Omega-3 fatty acids have anti-inflammatory effects in many chronic diseases. In CVID-8, they may help reduce background inflammation, joint pain, and support cardiovascular health, though they do not replace immunosuppressive drugs. Mechanistically, omega-3s are converted into lipid mediators that resolve inflammation rather than promote it. [33]

(Any supplement plan should be written down and checked against prescribed medicines to avoid interactions.)

Immunity-booster, regenerative, and stem-cell-related therapies

1. Optimized immunoglobulin replacement as a functional immune “booster”
For CVID-8, the safest and best-studied “immune boosting” is not herbal products but properly dosed IVIG or SCIG. By keeping IgG levels above a minimum target, infection rates drop and chronic lung damage is slowed. In this sense, IgG replacement functions as a regenerative support for immune function, because it reduces constant damage from infections and allows organs to recover. [34]

2. Targeted CTLA-4 pathway repair with abatacept
Abatacept can be seen as a molecular repair of the CTLA-4 pathway, which is disrupted in LRBA deficiency. By mimicking CTLA-4 action, abatacept restores immune “braking” and reduces destructive autoimmunity. Long-term follow-up studies show sustained improvement in many patients and lower disease activity scores. This type of targeted biologic therapy is a modern example of “functional immune regeneration”, even though it is not a stem-cell product. [35]

3. Hematopoietic stem cell transplantation (HSCT)
In very severe or treatment-resistant LRBA deficiency, allogeneic hematopoietic stem cell transplantation (bone-marrow transplant) may be considered. Donor stem cells replace the patient’s immune system, potentially curing the underlying defect. Case series and cohort studies show that many LRBA-deficient patients who survive HSCT achieve partial or complete remission and can stop many immunosuppressive medicines, though there is a significant early transplant-related risk and possible graft-versus-host disease. [36]

4. Future regenerative and gene-targeted approaches
Research is exploring gene-based therapies and more refined cell therapies for monogenic immunodeficiencies like LRBA deficiency. These approaches aim to correct the defective gene or modulate specific immune pathways with fewer side effects. At present, they are experimental and only available in research settings, but they represent a long-term hope for safer, more complete correction of CVID-8. [37]

Surgeries and major procedures

1. Hematopoietic stem cell transplantation (HSCT) as a curative procedure
HSCT is both a drug-supported procedure and a form of surgery-like intervention. It involves conditioning chemotherapy, infusion of donor stem cells, and long hospital stays. It is considered in patients with severe, life-threatening disease manifestations that do not respond to medical therapy. The reason to do HSCT is the chance of long-term cure or major remission, balanced against the risks of early transplant-related mortality, severe infections, and graft-versus-host disease. [38]

2. Splenectomy (surgical removal of the spleen)
In some patients with refractory autoimmune thrombocytopenia or hemolytic anemia, splenectomy may be considered once medical treatments have failed. The spleen is a major site where damaged blood cells and antibody-coated cells are removed, so removing it can improve platelet and red cell counts. However, splenectomy increases lifelong risk of severe infections by certain bacteria, so it is used cautiously, usually with ongoing IgG replacement and strong vaccination and antibiotic plans. [39]

3. Surgery for chronic lung damage (rare, selected cases)
Severe localized bronchiectasis or destroyed lung segments may occasionally require surgical resection to control repeated infections or bleeding. The decision is made together by thoracic surgeons, pulmonologists, and immunologists, only after maximizing medical therapies. The goal is to remove non-functional lung tissue that acts as a reservoir for infection, while preserving as much healthy lung as possible. [40]

4. Central venous access devices
Some patients need implanted ports or central lines to receive frequent IVIG or complex chemotherapy regimens. While not surgery in the classic sense, insertion of these devices is an invasive procedure. It is done to make repeated infusions safer and easier, but it also carries risks of infection and thrombosis, so care and hygiene are essential. [41]

Prevention and long-term protection

Because we cannot list every possible measure in detail here, these are 10 key prevention ideas, each of which should be adapted by your medical team:

Keep IgG levels in the target range with regular IVIG/SCIG, as this is the most proven way to prevent serious infections and protect lungs. [42]
Avoid live vaccines in the patient unless a specialist clearly advises otherwise, while ensuring that household contacts are fully vaccinated with recommended schedules. [43]
Treat respiratory infections early and aggressively according to your emergency plan, to prevent pneumonia and bronchiectasis. [44]
Regular specialist reviews (immunology, hematology, gastroenterology, pulmonology) to detect complications such as chronic lung disease, liver disease, or malignancy early. [45]
Routine blood tests to monitor blood counts, liver and kidney function, and immunoglobulin levels, especially when using immunosuppressive or biologic medicines. [46]
Dental and ENT care to control chronic infection sources. [47]
Avoid tobacco smoke and polluted air to protect lungs. [48]
Maintain good nutrition and physical activity appropriate for energy level and organ function. [49]
Written care plan for school or work, including infection precautions and what to do in emergencies. [50]
Discuss HSCT early in very severe disease, so that families understand both potential benefits and serious risks, and can plan at an appropriate center if needed. [51]

When to see doctors urgently

People with CVID-8 should be in regular follow-up with an immunology team even when well. However, urgent medical attention is needed if there is high fever, difficulty breathing, chest pain, confusion, very fast heart rate, or severe abdominal pain, as these may be signs of sepsis, pneumonia, or other emergencies. [52]

Other warning signs include sudden bruising, nosebleeds, or dark urine, which can signal autoimmune thrombocytopenia or hemolytic anemia; persistent, bloody diarrhea or weight loss, which can point to severe gut inflammation; and new, rapidly enlarging lymph nodes or unexplained weight loss, which may require urgent evaluation for lymphoproliferative disease or cancer. [53]

Families should have a clear written emergency plan, including when to call their immunology center, when to go straight to the nearest emergency department, and which documents (diagnosis letter, medication list, and last IgG level) to bring. [54]

What to eat and what to avoid

For CVID-8, there is no single magic diet, but some principles help protect general health and reduce complications. A balanced, varied diet with enough calories, protein, fruits, vegetables, and whole grains supports immune cells, wound healing, and growth. Soft, easy-to-digest foods may be needed during gut flares. [55]

People with gut involvement often feel better when they avoid highly processed foods, very spicy or greasy meals, and large amounts of caffeine or fizzy drinks, which can irritate the digestive tract. Food safety is also important: thoroughly cooked meat and eggs, safe drinking water, and careful food storage reduce the risk of foodborne infections. [56]

If there is proven lactose intolerance or celiac disease, specific avoidance (lactose-free or gluten-free diet) is needed. Salt intake should be limited, especially if steroids are used, to reduce swelling and high blood pressure. Alcohol and smoking should be avoided in older patients, as they worsen liver and lung problems. All major dietary changes and supplements should be discussed with the care team, particularly if the patient is underweight or has severe gut disease. [57]

Frequently asked questions

1. Is CVID-8 with autoimmunity curable?
Without stem cell transplantation, CVID-8 is usually a life-long condition. However, with modern IgG replacement, targeted biologics such as abatacept, and careful management of autoimmunity and infections, many patients can live active lives. In selected severe cases, HSCT may offer a potential cure but comes with serious risks and is not suitable for everyone. [58]

2. Why does my child have both infections and autoimmunity?
LRBA deficiency weakens antibody production (causing infections) and also removes “brakes” on T-cell activation (causing attacks against the body’s own cells). So the immune system is weak and mis-directed at the same time. [59]

3. Will immunoglobulin therapy stop the autoimmunity?
IgG replacement mainly targets infections. In some patients it may modestly improve autoimmunity, but most still need additional immunosuppressive or targeted drugs (like steroids, rituximab, or abatacept) to fully control autoimmune cytopenias or gut disease. [60]

4. Is rituximab safe in CVID-8?
Rituximab has been used in many CVID patients with good effect on autoimmune cytopenias and GLILD, but it does carry important risks such as infusion reactions, serious infections, and very rare brain infection (PML). These risks are carefully weighed against its benefits, and treatment is usually combined with IgG replacement and close monitoring. [61]

5. Why is abatacept so important for LRBA deficiency?
Because LRBA deficiency leads to reduced CTLA-4 on regulatory T cells, abatacept—a CTLA-4–Ig fusion protein—acts as a replacement brake for the immune system. Studies show it can significantly reduce autoimmune symptoms and lymphoproliferation in many LRBA-deficient patients. [62]

6. When should HSCT be considered?
HSCT is usually discussed when there is severe, life-threatening disease (such as uncontrollable autoimmunity, severe lung disease, or organ damage) despite optimized IgG replacement, targeted biologics, and conventional immunosuppression. International cohorts suggest many transplanted LRBA patients achieve major remission, but early transplant-related mortality remains significant, so the decision is complex. [63]

7. Can my child go to school normally?
Most children with CVID-8 can attend school with reasonable infection precautions, flexible absence policies, and close communication between parents, school, and the medical team. Extra care is needed during major viral outbreaks, when temporary home study may be safer. [64]

8. Will my child grow normally?
Growth depends on controlling infections, gut disease, and inflammation, and on providing good nutrition and hormone balance. With modern therapies, many children achieve near-normal growth, but close monitoring and early interventions (nutrition support, bone-health management, and sometimes endocrinology review) are important. [65]

9. Is pregnancy possible in CVID-8?
There are reports of women with CVID having successful pregnancies under careful specialist supervision, with continued IgG replacement and close monitoring. For LRBA deficiency specifically, pregnancy requires detailed planning due to autoimmunity, medications, and inheritance risk, and should be managed in a high-risk obstetric and immunology setting. [66]

10. Where can families find reliable information and support?
Families can get reliable information from national primary immunodeficiency organizations, peer-reviewed articles, and their own immunology centers. Patient advocacy groups for primary immunodeficiencies and CTLA-4/LRBA defects can provide emotional support, practical tips, and help in understanding new research and treatment options. [67]

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 13, 2025.

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