[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Immunology](https://durgical.com/en/immunology/) › [Immunodeficiencies](https://durgical.com/en/immunology/#a-immunodeficiency) › B-cell (antibody) deficiencies: XLA, CVID, IgA deficiency, hyper-IgM

[Immunology](https://durgical.com/en/immunology/) · [Immunodeficiencies](https://durgical.com/en/immunology/#a-immunodeficiency)

# 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

## Key points

- XLA: BTK mutation, X-linked; boys with almost no B cells (CD19), all immunoglobulins very low, small tonsils and lymph nodes, infections after 6 months.
- CVID: low IgG plus low IgA and/or IgM, B cells present but poor vaccine responses; usually diagnosed in the 20s–30s; autoimmunity (ITP, hemolytic anemia) and lymphoma.
- Selective IgA deficiency: the most common primary immunodeficiency; often silent; linked to celiac disease, Giardia and anaphylaxis to blood products with IgA.
- Hyper-IgM (CD40L defect, X-linked): normal or high IgM, low IgG, IgA and IgE; failed class switching; Pneumocystis and Cryptosporidium because T-cell help is also faulty.
- Enteroviruses and Giardia are the non-bacterial germs to remember in antibody deficiency.

## 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.

## Memory aid

Bruton boys have no B cells; CVID shows up in young adults; IgA deficiency is often silent until a transfusion; hyper-IgM is stuck in first gear and never switches.

## 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.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/immunology/b-cell-deficiencies-xla-cvid-iga-deficiency-hyper-igm/)

## Related

- [Immunodeficiency: warning signs and the infection pattern by defect](https://durgical.com/en/immunology/immunodeficiency-warning-signs-and-the-infection-pattern-by-defect/)
- [T-cell and combined deficiencies: DiGeorge, SCID, Wiskott–Aldrich, ataxia-telangiectasia](https://durgical.com/en/immunology/t-cell-and-combined-deficiencies-digeorge-scid-wiskott-aldrich-ataxia-telangiect/)
- [Secondary immunodeficiency: HIV, malnutrition, drugs, asplenia](https://durgical.com/en/immunology/secondary-immunodeficiency-hiv-malnutrition-drugs-asplenia/)

## Microorganisms

- [Streptococcus pneumoniae](https://durgical.com/en/microbiology/streptococcus-pneumoniae/)
- [Haemophilus influenzae](https://durgical.com/en/microbiology/haemophilus-influenzae/)
- [Giardia duodenalis](https://durgical.com/en/microbiology/giardia-duodenalis/)
- [Enteroviruses](https://durgical.com/en/microbiology/enteroviruses/)
- [Pneumocystis jirovecii](https://durgical.com/en/microbiology/pneumocystis-jirovecii/)
- [Cryptosporidium spp.](https://durgical.com/en/microbiology/cryptosporidium-spp/)

[← All of immunology](https://durgical.com/en/immunology/)

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](https://medlineplus.gov/genetics/condition/x-linked-agammaglobulinemia/) (MedlinePlus Genetics, U.S. National Library of Medicine, 2026); [Common variable immune deficiency](https://medlineplus.gov/genetics/condition/common-variable-immune-deficiency/) (MedlinePlus Genetics, U.S. National Library of Medicine, 2026); [X-linked hyper IgM syndrome](https://medlineplus.gov/genetics/condition/x-linked-hyper-igm-syndrome/) (MedlinePlus Genetics, U.S. National Library of Medicine, 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/immunology/b-cell-deficiencies-xla-cvid-iga-deficiency-hyper-igm/