Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees

J Allergy Clin Immunol. 2022 May;149(5):1525-1560. doi: 10.1016/j.jaci.2022.01.025. Epub 2022 Feb 14.


Secondary hypogammaglobulinemia (SHG) is characterized by reduced immunoglobulin levels due to acquired causes of decreased antibody production or increased antibody loss. Clarification regarding whether the hypogammaglobulinemia is secondary or primary is important because this has implications for evaluation and management. Prior receipt of immunosuppressive medications and/or presence of conditions associated with SHG development, including protein loss syndromes, are histories that raise suspicion for SHG. In patients with these histories, a thorough investigation of potential etiologies of SHG reviewed in this report is needed to devise an effective treatment plan focused on removal of iatrogenic causes (eg, discontinuation of an offending drug) or treatment of the underlying condition (eg, management of nephrotic syndrome). When iatrogenic causes cannot be removed or underlying conditions cannot be reversed, therapeutic options are not clearly delineated but include heightened monitoring for clinical infections, supportive antimicrobials, and in some cases, immunoglobulin replacement therapy. This report serves to summarize the existing literature regarding immunosuppressive medications and populations (autoimmune, neurologic, hematologic/oncologic, pulmonary, posttransplant, protein-losing) associated with SHG and highlights key areas for future investigation.

Keywords: B-cell–targeted therapy; CD19 CAR-T-cell therapy; Secondary hypogammaglobulinemia; autoimmunity; immunosuppression; immunosuppressive medication; ocrelizumab; protein loss; protein-losing enteropathy; rituximab; solid organ transplant.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Agammaglobulinemia* / diagnosis
  • Agammaglobulinemia* / etiology
  • Agammaglobulinemia* / therapy
  • Common Variable Immunodeficiency* / complications
  • Humans
  • Iatrogenic Disease
  • Immunity
  • Immunoglobulins
  • Immunologic Deficiency Syndromes* / complications
  • Immunologic Deficiency Syndromes* / diagnosis
  • Immunologic Deficiency Syndromes* / therapy


  • Immunoglobulins