Table 1 Primary and secondary causes of hypogammaglobulinemia to be distinguished from common variable immunodeficiency
Cause | Diagnosis (examples) |
|---|---|
Primary immunodeficiencies | Â |
Agammaglobulinemias | X-chromosomal agammaglobulinemia (BTK), rare AR forms |
Class switch recombination deficiencies | X-chromosomal form: CD40L |
| Â | Autosomal recessive forms: CD40, AID, UNG |
X-chromosome lymphoproliferative | SAP, XIAP deficiency |
syndrome | Â |
Combined immunodeficiency | Hypomorphic variants of severe combined immunodeficiencies |
| Â | Other forms of combined immunodeficiency (ORAI, STIM, DOCK8 a.o.) |
Other defined primary immunodeficiencies | WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome DiGeorge syndrome |
Chromosomal instability syndromes | Ataxia telangiectasia (ATM) |
| Â | Nijmegen breakage syndrome (NBS1) |
| Â | ICF (immunodeficiency, chromosomal instability, facial abnormalities) syndrome (DNMT3B) |
Secondary cause | Â |
Malignancy | Chronic lymphatic leukemia |
| Â | Immunodeficiency and thymoma (Good syndrome) |
| Â | Malignant lymphoma |
Protein loss | Loss of immunoglobulins (for example, renal or gastrointestinal protein loss, severe burns, lymphangiectasis) |
| Â | Hyperkatabolism of immunoglobulins (for example, myotonic dystrophy types 1 and 2) |
Drug induced | Anticonvulsants (carbamazepine, valproic acid, phenytoine) |
| Â | Sulfasalazine |
| Â | Gold salts |
| Â | Glucocorticoids |
| Â | Azathioprine |
| Â | D-Penicillamine |
| Â | Antimalarial agents (very rare) |
| Â | Methotrexate (very rare) |
| Â | Alkylating agents (cyclophosphamid, chlorambucil) |
| Â | Anti-CD20 (rituximab) |
| Â | Imatinib |
Infectious | Congenital cytomegalovirus, rubella or Toxoplasma gondii infection, neonatal HIV infection |
| Â | Ebstein-Barr virus infection |