Immunology · Immunodeficiencies
B-cell (antibody) deficiencies: XLA, CVID, IgA deficiency, hyper-IgM !
- Topic
When the body cannot make enough antibodies, bacteria with a capsule keep causing ear, sinus and lung infections.
Updated 2026-11-01
What it is
Antibody deficiencies are the most common primary immunodeficiencies. B cells may be absent (XLA), present but unable to make enough antibody (CVID, IgA deficiency) or unable to switch from IgM to other classes (hyper-IgM syndrome). Infections are mostly sinopulmonary and caused by encapsulated bacteria; some forms add gut infections, autoimmunity and lymphoma.
Antibody deficiencies: the table to know
| Disease | Defect (gene, inheritance) | What is low | Infections and clues | Key test |
|---|---|---|---|---|
| X-linked (Bruton) agammaglobulinemia | BTK tyrosine kinase; X-linked recessive (boys) | Mature B cells absent; all immunoglobulin classes very low | Pneumonia, sinusitis, otitis from encapsulated bacteria after 6 months; enteroviral meningoencephalitis; Giardia; tiny tonsils and nodes | Flow cytometry: CD19 B cells almost absent; very low IgG, IgA, IgM |
| Common variable immunodeficiency (CVID) | Unknown in most cases; some TNFRSF13B (TACI); usually sporadic | IgG plus IgA and/or IgM; B cells normal in number | Sinopulmonary infections, bronchiectasis, chronic diarrhea; autoimmune cytopenias; granulomas; lymphoma and gastric cancer risk | Low immunoglobulins with poor vaccine antibody response |
| Selective IgA deficiency | Mostly unknown; often familial | IgA only; IgG and IgM normal | Often none; sinopulmonary and gut infections, Giardia, celiac disease, autoimmunity; anaphylaxis to blood products containing IgA | Very low serum IgA with normal IgG and IgM (after age 4) |
| Hyper-IgM syndrome | CD40 ligand on T cells (CD40LG); X-linked recessive is the most common form | IgG, IgA, IgE low; IgM normal or high | Encapsulated bacteria plus Pneumocystis and Cryptosporidium (with liver and bile duct disease); neutropenia | Immunoglobulin pattern; CD40L expression on activated T cells by flow cytometry |
| Transient hypogammaglobulinemia of infancy | Delayed maturation; not genetic in most | IgG low for age, recovers | Mild recurrent infections; normal vaccine responses | Repeat immunoglobulins over time; resolves in early childhood |
Clinical notes
- Immunoglobulin replacement (IV or subcutaneous) is the standard treatment for XLA, CVID and other defects with failing IgG.
- Live vaccines are avoided in XLA; oral polio vaccine has caused vaccine-associated paralysis in these patients.
- Patients with selective IgA deficiency who develop anti-IgA antibodies can react severely to transfusions; washed products or IgA-deficient donor products are used.
- IgG replacement is not given for isolated IgA deficiency, because the products contain little IgA and the missing antibody is mucosal.
In the lab
- Serum IgG, IgA, IgM compared with age-specific ranges.
- Specific antibody response to protein (tetanus) and polysaccharide (pneumococcal) vaccines.
- B-cell enumeration (CD19 or CD20) by flow cytometry.
Test yourself
Think of the answer, then tap the question to see it.
A 9-month-old boy has recurrent pneumonia, absent tonsils and almost no CD19 cells. What is the most likely diagnosis and gene?
X-linked (Bruton) agammaglobulinemia, caused by a BTK mutation that blocks B-cell maturation.
Why does a patient with hyper-IgM syndrome have high IgM but low IgG, IgA and IgE?
CD40 ligand on T cells is defective, so B cells do not receive the signal to switch class; they keep making IgM.
Which primary immunodeficiency is the most common and is linked to anaphylaxis after transfusion?
Selective IgA deficiency; some patients form anti-IgA antibodies that react with IgA in donor blood.
Which non-infectious complications are typical of common variable immunodeficiency?
Autoimmune cytopenias (ITP, autoimmune hemolytic anemia), granulomas, bronchiectasis and an increased risk of lymphoma.
Related
- Immunodeficiency: warning signs and the infection pattern by defect
- T-cell and combined deficiencies: DiGeorge, SCID, Wiskott–Aldrich, ataxia-telangiectasia
- Secondary immunodeficiency: HIV, malnutrition, drugs, asplenia
Microorganisms
- Streptococcus pneumoniae
- Haemophilus influenzae
- Giardia duodenalis
- Enteroviruses
- Pneumocystis jirovecii
- Cryptosporidium spp.
Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.
Sources: X-linked agammaglobulinemia (MedlinePlus Genetics, U.S. National Library of Medicine, 2026); Common variable immune deficiency (MedlinePlus Genetics, U.S. National Library of Medicine, 2026); X-linked hyper IgM syndrome (MedlinePlus Genetics, U.S. National Library of Medicine, 2026).
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Representative model, for educational purposes only.