Immune Dysregulation with Autoimmunity and Immunodeficiency

Immune dysregulation with autoimmunity and immunodeficiency means the body’s defense system is out of balance in two ways at the same time. First, it is over-active against the self (autoimmunity), so it may attack blood cells, the gut, the joints, the skin, lungs, or other organs. Second, it is under-active against germs (immunodeficiency), so infections can happen more often or more severely. In many people this happens because of changes in genes that control immune “brakes” and “traffic lights,” so the system cannot calm down properly or target the right threats. Doctors sometimes call these conditions primary immune regulatory disorders (PIRDs) or “inborn errors of immunity” with prominent autoimmunity. PubMed+2Frontiers+2

Immune dysregulation with autoimmunity and immunodeficiency means the immune system loses its balance. Parts that should protect you from infection are weak (immunodeficiency), while parts that should tolerate your own tissues become overactive and attack your body (autoimmunity). Many of these conditions are now grouped as Primary Immune Regulatory Disorders (PIRDs) or Inborn Errors of Immunity (IEI). They are often caused by single-gene changes that disturb immune “brakes” (such as CTLA-4 and LRBA) or signaling pathways that keep inflammation under control. People may come to the doctor first with autoimmune problems (like low blood cells, gut inflammation, thyroid disease) and only later show infections, or both can happen together. PubMed+2PMC+2

These conditions are not rare curiosities anymore: the official international classification is updated regularly and now lists hundreds of genes linked to immune dysregulation, with new ones added each year. Doctors use these lists to match symptoms and lab results to the right diagnosis and to guide testing and treatment. iuis.org+3PubMed+3PubMed+3

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Other names

You may see several names that refer to the same overall idea:

• Primary immune regulatory disorders (PIRDs) – a group name for conditions where loss of immune control causes autoimmunity, hyper-inflammation, and often infections. Frontiers+1

• Inborn errors of immunity (IEI) with autoimmunity – the formal, gene-based classification used worldwide. PubMed+1

• Primary immunodeficiency with autoimmunity – an older clinical label highlighting that autoimmunity can be the first sign of an underlying immunodeficiency (for example, in CVID). Lippincott Journals+1

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Types

Doctors often sort these conditions by the main immune control that is broken. A few common “type” buckets:

1. Checkpoint defects in T-cell regulation – for example CTLA-4 haploinsufficiency or LRBA deficiency, which reduce the “brakes” on immune responses and lead to lymphoproliferation, cytopenias, enteropathy, and infections. PMC+2Frontiers+2

2. Regulatory T-cell (Treg) pathway problems – broad group; when Tregs are too few or don’t work, self-tolerance fails and autoimmunity appears early and often. PMC

3. Cytokine signaling dysregulation – pathways such as STAT3 gain-of-function or PI3K-delta activation can drive chronic inflammation and autoimmunity while predisposing to infection. (Overview category within PIRD/IEI frameworks.) Frontiers+1

4. Defects in B-cell maturation and antibody production – classic CVID where low immunoglobulins cause infections, and autoimmunity (especially autoimmune cytopenias) is common. NCBI+2PMC+2

5. Impaired immune “off-switches”/cell death – conditions that blunt normal shutdown of responses, leading to lymphoproliferation and autoimmunity. (Concept summarized in PIRD reviews.) BioMed Central

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Causes

Below are 20 common causes or cause-categories. Many are monogenic (single-gene) disorders recognized by the international IEI list.

1. CTLA-4 haploinsufficiency: missing half the normal CTLA-4 “brake” lets T cells stay active too long, causing lymph node enlargement, low blood counts, gut inflammation, and infections. PMC+1

2. LRBA deficiency: LRBA normally helps keep CTLA-4 on the cell surface. Without LRBA, CTLA-4 is lost inside the cell, removing a key brake and driving autoimmunity and infections. PubMed+1

3. STAT3 gain-of-function: overactive STAT3 signaling pushes autoimmune responses and increases infection risk. (PIRD/IEI category.) Frontiers

4. PIK3CD/PIK3R1 variants (Activated PI3K-δ syndrome): dysregulated PI3K signaling causes recurrent infections, swollen nodes/spleen, and autoimmunity. (IEI framework.) PubMed

5. FOXP3 pathway defects (regulatory T-cell problems): when Tregs fail, the immune system attacks self; infections may also occur. (PIRD concept.) PMC

6. CVID (common variable immunodeficiency): poor antibody production leads to infections; autoimmunity—especially autoimmune cytopenias and thyroid disease—is frequent. NCBI+1

7. XIAP deficiency and related apoptosis/cell-death defects: failure to properly end immune responses can drive inflammation and autoimmunity with infection susceptibility. (IEI category overview.) PubMed

8. DOCK8 deficiency and combined immunodeficiencies: impaired cell signaling and barrier immunity permit infections; autoimmunity may occur. (IEI framework.) PubMed

9. Complement pathway defects: poor clearance of immune complexes and dying cells may promote autoimmunity alongside infections. (IUIS phenotypic lists.) PubMed

10. Cytokine pathway imbalances (e.g., IL-2/IL-10 axis): disturbed anti-inflammatory signals allow uncontrolled inflammation and autoimmunity. (PIRD reviews.) Frontiers

11. Perforin/cytotoxicity pathway defects: when killer cells cannot turn off immune responses by removing activated cells, hyper-inflammation and autoimmunity can occur. BioMed Central

12. T-cell receptor signaling defects: skewed activation can produce both susceptibility to infection and autoimmune features. (IEI overview.) PubMed

13. B-cell tolerance defects: faulty elimination of self-reactive B cells fosters autoantibodies and infections due to poor protective antibodies. (CVID + IEI concepts.) PMC

14. Checkpoint phenocopies (autoantibodies against checkpoints): rare patients make antibodies that block their own immune brakes, acting like a genetic defect. PubMed

15. Environmental triggers on genetic background: infections or vaccines rarely unmask underlying PIRD; the genetic predisposition is the main driver. (PIRD overview.) PubMed

16. Hematopoietic stem-cell niche and maturation defects: abnormal lymphocyte development can present with autoimmunity and infections. (IEI umbrella.) PubMed

17. Dysregulated germinal center formation: poor quality control during antibody maturation leads to autoantibodies and weak protective antibodies. (CVID literature.) PMC

18. Immune dysregulation in the gut (enteropathy-dominant PIRDs): genes affecting barrier and T-cell control can cause Crohn-like colitis plus infections. (PIRD reviews, LRBA case series.) PubMed

19. Neurologic involvement from systemic dysregulation: some PIRDs cause brain/spinal cord inflammation along with systemic autoimmunity. (LRBA CNS reports; CTLA-4 neurologic series.) PMC+1

20. Newly discovered IEI genes each year: continuous updates expand the known causes and explain previously “mystery” combinations of autoimmunity + infections. RUPress

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Symptoms and clinical clues

1. Unusual autoimmunity at a young age (for example, autoimmune anemia or low platelets): common front-door sign of a PIRD/IEI. PubMed

2. Recurrent or severe infections (ear, sinus, lungs, gut, skin): reflect underlying immunodeficiency. NCBI

3. Swollen lymph nodes and enlarged spleen/liver (lymphoproliferation): the immune system is “stuck on.” Frontiers

4. Chronic diarrhea or inflammatory colitis (enteropathy): gut autoimmunity or dysregulated inflammation. PubMed

5. Rashes and eczema-like skin disease: cutaneous autoimmunity or chronic infection/inflammation. (PIRD overviews.) PubMed

6. Thyroid autoimmunity or other endocrine problems: frequent in immune dysregulation disorders and CVID. PMC

7. Failure to thrive or poor weight gain in children: signals chronic inflammation or infections. PubMed

8. Mouth ulcers or autoimmune mucosal problems: seen in CVID and checkpoint defects. PMC

9. Autoimmune joint pain/swelling (arthritis): part of the hyper-inflammatory phenotype. PubMed

10. Breathing problems or chronic cough: can signal bronchiectasis from infections or lung autoimmunity—often checked by HRCT. NCBI

11. Neurologic symptoms (headache, seizures, weakness): possible CNS inflammation in some PIRDs. PMC+1

12. Autoimmune thyroid, celiac-like disease, or other organ-specific autoimmunity: frequently reported in CVID with autoimmunity. PMC

13. Fever and high inflammatory markers without clear infection: points to immune over-activation. (PIRD overview.) Frontiers

14. Recurrent pneumonia or sinusitis despite standard care: suggests antibody deficiency with or without autoimmunity. NCBI

15. Combination of multiple autoimmune conditions in the same person (polyautoimmunity): a strong clue to an underlying PIRD/IEI. PubMed

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Diagnostic tests

A) Physical examination (what the clinician looks for)

1. Growth and nutrition check: poor weight gain or height may indicate chronic inflammation or infection. PubMed

2. Lymph nodes, spleen, and liver exam: enlargement suggests lymphoproliferation from checkpoint/Treg disorders. Frontiers

3. Skin, hair, and nails inspection: rashes, alopecia, and nail changes can reflect autoimmunity. (CVID autoimmune literature.) PMC

4. Joint exam (swelling, warmth, range of motion): signs of autoimmune arthritis or inflammation. (PIRD clinical features.) PubMed

5. Neurologic screening (strength, reflexes, sensation): looks for CNS or peripheral nerve inflammation in selected PIRDs. PMC

B) Manual/bedside tests and procedures

6. Stool occult blood and fecal calprotectin: quick screens for gut inflammation in suspected enteropathy. (Enteropathy in LRBA/PIRD context.) PubMed

7. Pulmonary function tests (spirometry): identify airway damage from infections or inflammation; guide imaging. NCBI

8. Basic vision/cranial nerve checks: simple bedside screening if neurologic symptoms are present. (PIRD neurology reports.) PMC

9. Bedside ultrasound (where available): assesses spleen/liver size and lymph nodes to track lymphoproliferation. (General PIRD care concept.) PubMed

C) Laboratory and pathology tests

10. Complete blood count (CBC) with smear: looks for autoimmune cytopenias (low red cells, platelets, or neutrophils) and infection-related changes. (CVID/PIRD autoimmune focus.) PMC

11. Quantitative immunoglobulins (IgG, IgA, IgM): low levels suggest antibody deficiency such as CVID; patterns can guide further testing. NCBI

12. Specific antibody titers (vaccine responses): poor response to vaccines supports humoral immunodeficiency. (CVID evaluation standards.) NCBI

13. Autoantibodies (e.g., ANA, anti-dsDNA, anti-TPO) and direct antiglobulin (Coombs) test: mark tissue-specific autoimmunity and autoimmune cytopenias. (Autoimmunity in IEI/CVID.) PMC

14. Lymphocyte subsets by flow cytometry (T, B, NK cells; switched memory B cells): patterns support diagnoses like CVID and checkpoint defects. NCBI

15. Functional lymphocyte assays (proliferation, cytokine signaling panels): detect pathway problems (e.g., STAT3/PI3K dysregulation) that fit PIRD categories. Frontiers

16. Genetic testing (targeted panels/exome): confirms monogenic causes listed by IUIS/IEI, connects symptoms to a specific gene, and guides therapy. PubMed+1

17. Treg/CTLA-4 expression studies (where available): support CTLA-4/LRBA diagnoses and explain loss of immune “brakes.” PMC+1

18. Endoscopy with biopsies for chronic diarrhea: documents autoimmune enteropathy and rules out chronic infection. (LRBA/enteropathy literature.) PubMed

D) Electrodiagnostic tests

19. EMG/NCS (electromyography/nerve conduction studies): applied if there is suspected autoimmune neuropathy or myopathy linked to immune dysregulation. (Neurologic involvement case literature.) PMC

20. EEG (electroencephalography): used in seizure or encephalopathy evaluation where autoimmune CNS inflammation is suspected in PIRDs. (CTLA-4 neurologic series.) American Academy of Neurology

E) Imaging tests (often chosen based on symptoms)

• High-resolution CT (HRCT) chest: checks for bronchiectasis or interstitial lung disease in CVID or PIRD. NCBI

• CT/MRI abdomen: evaluates spleen/liver size and lymph nodes for lymphoproliferation. (PIRD clinical assessment.) PubMed

• Brain MRI: evaluates suspected CNS inflammation in checkpoint/Treg pathway diseases. American Academy of Neurology

Non-pharmacological treatments

1. Vaccination planning (safe schedule): People with significant immune deficiency should avoid live vaccines but receive all recommended inactivated vaccines (and household members should be fully vaccinated to create a protective “cocoon”). Your specialist individualizes the plan by your exact diagnosis. CDC+2CDC+2

Purpose: reduce severe infections that can trigger autoimmune flares.
Mechanism: primes safer arms of immunity without risking live-vaccine replication.

2. Infection prevention routines: Hand hygiene, mask use during outbreaks, prompt dental care, skin/wound care, safe food/water, and early antibiotics when advised. HEPA home filtration may help airway health in recurrent lung disease. PubMed

Purpose: fewer infections → fewer immune “alarms.”
Mechanism: lowers pathogen exposure and secondary inflammation.

3. Pulmonary rehabilitation (for GLILD/airway disease): Guided breathing exercises, airway clearance, endurance training, and energy-conservation coaching improve function and reduce breathlessness. PMC

Purpose: better lung capacity and daily activity.
Mechanism: strengthens respiratory muscles; improves mucus clearance and oxygen use.

4. Nutrition optimization: Balanced, Mediterranean-style eating (fish/legumes/whole grains/vegetables/olive oil) supports immune health and reduces systemic inflammation; address iron, B12, folate, or vitamin D deficiency if present. BMJ

Purpose: support healing and steady energy.
Mechanism: anti-inflammatory nutrients, improved gut barrier and microbiome balance.

5. Structured sleep: 7–9 hours nightly with consistent timing improves infection resistance and reduces pain/fatigue. Sleep apnea screening if snoring/daytime sleepiness. PubMed

Purpose: restore immune rhythm.
Mechanism: sleep normalizes cytokines and T-cell function.

6. Graduated physical activity: Low-impact aerobic movement and gentle strength work (as tolerated) improve stamina, bone health (steroids can thin bone), and mood. PubMed

Purpose: reduce fatigue and steroid side effects.
Mechanism: anti-inflammatory myokines, improved insulin sensitivity.

7. Stress-management skills: Brief CBT, mindfulness, breathing drills, or guided imagery can reduce flare triggers related to stress. PubMed

Purpose: lower flare frequency.
Mechanism: calmer autonomic tone; reduced stress hormones.

8. Sun protection/skin care: Barrier creams for eczema-type rashes; sunscreen for photosensitive rashes; avoid skin trauma when platelets are low. PubMed

9. Bone protection plan: Calcium/vitamin D adequacy, weight-bearing exercise, and periodic bone-density checks if long-term steroids are needed. PubMed

10. Anemia/bleeding safety plan: Injury avoidance, soft toothbrush, prompt evaluation of dark stools or unusual bruising. PubMed

11. Germ-exposure budgeting: Plan work/school with sick-day rules; consider seasonal masking or remote options during surges. PubMed

12. Allergy avoidance and asthma control if present; good control reduces infection risk and lung flares. PubMed

13. Smoking cessation and alcohol moderation to protect lungs/liver and lower infection risk. PubMed

14. Dental schedule every 6 months (or more) to prevent bacteremia from gum disease. PubMed

15. Physical/occupational therapy for joint pain and fatigue pacing. PubMed

16. Heat–cold symptom tools: Warm packs for joint stiffness, cool packs for inflamed joints; safe use only. PubMed

17. Travel planning: Vaccines/antibiotics advice in advance; avoid high-risk exposures. CDC

18. Household vaccine strategy: Make sure family receive MMR/varicella/zoster (live) and all inactivated vaccines; avoid oral polio in household members. Guideline Central

19. Medication safety education: Early reporting of fever, cough, jaundice, unusual bruising while on immunosuppressants. PubMed

20. Support groups/psychosocial care to handle chronic-illness stress and improve adherence. PubMed

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Drug treatments

Doses and choices are individualized to your diagnosis, weight, organ involvement, and infection risk. Never start/stop without your clinician.

1. Immunoglobulin replacement (IVIG/SCIG): Replaces missing antibodies in many with CVID or antibody defects, preventing infections and sometimes calming inflammation. Typical IVIG dose ~400–600 mg/kg every 3–4 weeks (higher troughs for lung disease); SCIG is an at-home alternative. Side effects: headache, infusion reactions; rare thrombosis/aseptic meningitis. Medscape

2. Corticosteroids (e.g., prednisone): Short courses to control severe flares (e.g., autoimmune cytopenias, colitis, GLILD). Risk: weight gain, high sugar, bone loss, infection. Aim for steroid-sparing plans. Frontiers

3. Rituximab (anti-CD20): Depletes B cells; helpful for autoimmune cytopenias and GLILD in CVID; often combined with IVIG. Dosing varies (e.g., 375 mg/m² weekly ×4 or 1,000 mg ×2). Risks: infusion reactions, prolonged low IgG, infections; screen for hepatitis B. PMC+1

4. Sirolimus (mTOR inhibitor): First-line steroid-sparing drug in ALPS and other lymphoproliferative autoimmunity. Monitors include drug levels, lipids, kidney function. Risks: mouth sores, high lipids, infection. F1000Research+1

5. Abatacept (CTLA4-Ig): Replaces a missing immune “brake” in CTLA-4 haploinsufficiency/LRBA deficiency; can calm colitis, cytopenias, lymphoproliferation. Dosing is weight-based IV or weekly SC. Risks: infections, infusion reactions. PMC+1

6. Mycophenolate mofetil: Common steroid-sparing agent for cytopenias/colitis. Risks: low white counts, GI upset, teratogenic. PubMed

7. Azathioprine: Alternative steroid-sparing drug; test TPMT activity first. Risks: marrow suppression, liver injury. PubMed

8. Methotrexate (low-dose weekly): For arthritis/skin/gut inflammation with careful monitoring and folate. Risks: liver toxicity, marrow suppression. PubMed

9. JAK inhibitors (ruxolitinib, tofacitinib, baricitinib): Helpful in STAT3 GOF and some PIRD-related inflammation (including lung disease). Risks: shingles, clots (depends on agent), lipids—needs close oversight. PMC+2PMC+2

10. IL-6 blockade (tocilizumab): Can reduce inflammation in STAT3-skewed disease; monitor liver tests, lipids. ResearchGate

11. Antimicrobial prophylaxis: Low-dose antibiotics/antivirals/antifungals in selected patients to prevent infections while immunosuppressed. Risks: resistance, side effects. Immune Deficiency Foundation

12. TMP-SMX (PJP prophylaxis): Considered when high-dose steroids or certain biologics are used. Risks: allergy, low counts. PubMed

13. G-CSF (for neutropenia): Boosts neutrophils in severe/refractory cases. Risks: bone pain, spleen enlargement (rare). PubMed

14. IVIG for autoimmunity control: Beyond infection prevention, high-dose IVIG can modulate autoimmunity in select flares. Risks: as above. ScienceDirect

15. Hydroxychloroquine: For rash/arthritis; monitor eyes. Risks: retinal toxicity (rare with monitoring). PubMed

16. Vedolizumab/anti-integrin for colitis: Gut-selective biologic when colitis dominates and infections must be minimized. Risks: infections (generally lower systemic risk). PubMed

17. TNF inhibitors (careful selection): May help certain organ inflammation but can increase infection risk; specialist decision only. PubMed

18. Calcineurin inhibitors (tacrolimus/cyclosporine): Sometimes used for severe autoimmunity; monitor kidneys and blood pressure. PubMed

19. Celiac-style diet plus budesonide for small-bowel-dominant disease: In highly selected cases under GI supervision. PubMed

20. Combination therapy (e.g., rituximab + IVIG for severe autoimmunity): Used in refractory cases with careful infection monitoring. PMC

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Dietary molecular supplements

1. Vitamin D (often 1000–2000 IU/day unless lab-guided): Supports balanced immunity; avoid deficiency. Function/mechanism: modulates T and B cells, promotes tolerance; RCT data (VITAL) suggest reduced new autoimmune diseases with 2000 IU/day in older adults. Note: dose should be blood-test guided; avoid excess. PMC+2BMJ+2

2. Omega-3 (EPA/DHA ~1 g/day from food or supplement): Anti-inflammatory lipid mediators (resolvins). Evidence supports benefit in several autoimmune conditions; however high-dose fish-oil supplements may raise atrial fibrillation/stroke risk in people without heart disease—food sources are preferred unless your doctor advises. Frontiers+1

3. Folate/B12/iron (as needed): Corrects deficiency in cytopenias or chronic gut disease; supports red-cell production. PubMed

4. Calcium + vitamin D for bone health: Important if on steroids. PubMed

5. Zinc (short courses if low): Supports barrier immunity; excessive dosing can lower copper. PubMed

6. Probiotics (case-by-case): May modulate gut inflammation, but live microbe products can rarely cause bacteremia in immunocompromised patients; only use if your specialist approves. MDPI+1

7. Curcumin (dietary spice/extract under guidance): Anti-inflammatory effects shown in small studies; watch for interactions. PubMed

8. Fiber/prebiotics (food-first): Feeds beneficial gut microbes that produce anti-inflammatory short-chain fatty acids. PubMed

9. Selenium (if deficient): Antioxidant roles for thyroid and immune function; avoid excess. PubMed

10. Multinutrient approach via whole foods: Emphasize diverse plants, legumes, nuts, fish; supplements fill gaps only after testing. BMJ

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Immunity-booster / regenerative / stem-cell” therapies

1. Allogeneic hematopoietic stem-cell transplantation (HSCT): Curative for IPEX and used selectively for severe CTLA-4/LRBA, ALPS, or other PIRDs when medical therapy fails. Mechanism: replaces defective immune system; Risks: graft-versus-host disease, infections. PMC+1

2. Gene therapy (condition-specific, research/center-based): Established for some classic immunodeficiencies; under study for regulatory disorders. Mechanism: corrects or compensates for the faulty gene in immune cells. PubMed

3. JAK-pathway targeted regeneration of balance (JAK inhibitors): Not “regenerative,” but can reset overactive signaling in STAT3-GOF to restore tolerance. Risks: infections, lipids, thrombosis (agent-specific). PMC

4. IL-6 receptor blockade (tocilizumab) in STAT-skewing: Can dampen inflammatory loops to protect organs while other therapies work. ResearchGate

5. mTOR modulation (sirolimus) in ALPS-type lymphoproliferation: Reduces abnormal lymphocyte survival and autoimmunity. F1000Research

6. Intensive IVIG (immunomodulatory dosing) in select flares: Temporarily “re-educates” immune networks. ScienceDirect

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Surgeries

1. Lymph node/organ biopsy: To confirm the diagnosis (e.g., GLILD) or exclude lymphoma when imaging is unclear. Why: guides correct therapy. PMC

2. Splenectomy (rare now): Considered for life-threatening, treatment-refractory immune thrombocytopenia/hemolysis; increases lifelong infection risk—vaccination and prophylaxis required. Why: stops spleen-mediated destruction. PubMed

3. Central line placement: For patients needing long-term IV therapies; requires strict infection prevention. Why: reliable access for IVIG/biologics. PubMed

4. Feeding tube (select pediatric cases): For severe malnutrition during uncontrolled colitis while treatments take effect. Why: maintain growth and medication delivery. PubMed

5. HSCT procedure (see above): Curative intent for specific PIRDs. Why: rebuilds the immune system. JA Connections

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Prevention tips

1. Personalized vaccine plan; avoid live vaccines if severely immunocompromised. 2) Keep household fully immunized (avoid oral polio at home). 3) Prompt antimicrobial prophylaxis when advised. 4) Hand hygiene and sick-day masks. 5) Dental and skin care routines. 6) Nutrition and vitamin D sufficiency; prefer omega-3 from food. 7) Sleep and regular activity. 8) No smoking, moderate alcohol. 9) Travel prep with your clinic. 10) Medication safety plan (what to do with fever or bleeding). bmjmedicine.bmj.com+3CDC+3Guideline Central+3

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When to see a doctor (or urgent care)

Seek care urgently for fever ≥38.0 °C, shortness of breath, chest pain, confusion, severe abdominal pain, uncontrolled bleeding/bruising, blood in stool/vomit, or rapid swelling of lymph nodes/spleen. Arrange routine follow-up every 3–6 months (or as directed) to monitor blood counts, immunoglobulins, lung/gut/skin symptoms, and medication side effects—especially if you receive steroids, rituximab, JAK inhibitors, sirolimus, or abatacept. PubMed

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What to eat & what to avoid

1. Emphasize Mediterranean-style meals: vegetables, fruits, legumes, whole grains, nuts, olive oil, and fish 1–2×/week. 2) Adequate protein (fish, poultry, legumes, eggs) for healing. 3) Vitamin-D-rich foods (fatty fish, fortified dairy) and test-guided supplements. 4) High-fiber foods for gut health. 5) Hydration for energy and mucus clearance. 6) Limit ultra-processed foods and added sugars. 7) Cook meats thoroughly; avoid unpasteurized products to lower infection risk. 8) Prefer omega-3 from food (fish, flax, walnuts); be cautious with high-dose fish-oil pills without medical advice. 9) Alcohol in moderation only (or avoid if on hepatotoxic drugs). 10) Discuss probiotics with your specialist before use. BMJ+2bmjmedicine.bmj.com+2

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FAQs

1. Is this the same as “autoimmune disease” alone?
   No. Here, autoimmunity and immunodeficiency coexist, so treatment must protect against infection and calm self-attack. PubMed

2. Can it be cured?
   Some forms (like IPEX) can be cured with HSCT; others are manageable long-term with targeted medicines and IVIG. PMC

3. Why do I get infections and autoimmunity together?
   The same faulty “brakes” that fail to stop self-attack also misdirect defenses against germs. Frontiers

4. Is genetic testing important?
   Yes—finding the exact gene (e.g., CTLA4, LRBA, FOXP3, STAT3) can unlock precision therapy (abatacept, JAK inhibitors, HSCT). JA Connections+1

5. Will IVIG fix autoimmunity?
   IVIG mainly prevents infections, but higher-dose IVIG can modulate autoimmunity in certain flares. Medscape+1

6. Are steroids safe?
   Short courses help, but long-term use raises infection, bone loss, diabetes risk; doctors aim for steroid-sparing plans. Frontiers

7. What is abatacept?
   A biologic that restores CTLA-4 “brake” signaling; useful in CTLA-4/LRBA-related disease. PMC

8. What is sirolimus?
   An mTOR inhibitor that is highly effective in ALPS for swollen nodes/spleen and cytopenias. F1000Research

9. What are JAK inhibitors for?
   They quiet overactive STAT-pathway signals (like STAT3 GOF) and can improve lung, gut, blood, and skin disease in selected patients. PMC

10. If I take rituximab, will I need more IVIG?
    Possibly—B-cell depletion can lower antibodies; clinicians often use IVIG and monitor infections. PMC

11. Are probiotics safe for me?
    Sometimes, but live probiotics have rare risks of bloodstream infection in immunocompromised people—ask your specialist first. MDPI

12. Should I take fish-oil capsules?
    Food sources are preferred. Recent data link regular fish-oil supplements to a higher risk of atrial fibrillation/stroke in otherwise healthy adults; benefits may differ if you already have heart disease. Discuss dosing with your doctor. bmjmedicine.bmj.com

13. Can diet alone control this?
    Diet supports therapy but usually cannot replace targeted medicines in PIRDs. Frontiers

14. Will I need surgery?
    Usually no. Surgery is for diagnosis (biopsy) or rare complications; HSCT is considered for specific severe gene-defined diseases. JA Connections

15. What specialists should I see?
    An immunologist plus organ-specific teams (hematology, pulmonology, gastroenterology, rheumatology) familiar with inborn errors of immunity. Frontiers

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: September 29, 2025.

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