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Table 1 Primary and secondary causes of hypogammaglobulinemia to be distinguished from common variable immunodeficiency

From: Common variable immunodeficiency - an update

Cause Diagnosis (examples)
Primary immunodeficiencies  
Agammaglobulinemias X-chromosomal agammaglobulinemia (BTK), rare AR forms
Class switch recombination deficiencies X-chromosomal form: CD40L
  Autosomal recessive forms: CD40, AID, UNG
X-chromosome lymphoproliferative SAP, XIAP deficiency
Combined immunodeficiency Hypomorphic variants of severe combined immunodeficiencies
  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)
  Nijmegen breakage syndrome (NBS1)
  ICF (immunodeficiency, chromosomal instability, facial abnormalities) syndrome (DNMT3B)
Secondary cause  
Malignancy Chronic lymphatic leukemia
  Immunodeficiency and thymoma (Good syndrome)
  Malignant lymphoma
Protein loss Loss of immunoglobulins (for example, renal or gastrointestinal protein loss, severe burns, lymphangiectasis)
  Hyperkatabolism of immunoglobulins (for example, myotonic dystrophy types 1 and 2)
Drug induced Anticonvulsants (carbamazepine, valproic acid, phenytoine)
  Gold salts
  Antimalarial agents (very rare)
  Methotrexate (very rare)
  Alkylating agents (cyclophosphamid, chlorambucil)
  Anti-CD20 (rituximab)
Infectious Congenital cytomegalovirus, rubella or Toxoplasma gondii infection, neonatal HIV infection
  Ebstein-Barr virus infection
  1. AID, activation-induced cytidine deaminase; a.o., and others; AR, autosomal recessive; ATM, ataxia telangiectasia mutated; BTK, Bruton agammaglobulinemia tyrosine kinase; DNMT3B, DNA (cytosine-5-)-methyltransferase 3 beta; DOCK8, dedicator of cytokinesis 8; NBS1, Nijmegen breakage syndrome 1; ORAI, ORAI calcium release-activated calcium modulator 1; SAP, SLAM associated protein/SH2 domain protein 1A; STIM, stromal interaction molecule 1; UNG, uracil-DNA glycosylase; XIAP, X-linked inhibitor of apoptosis.