Journal of Clinical Immunology

, Volume 28, Supplement 1, pp 62–66 | Cite as

Autoimmunity in Hyper-IgM Syndrome

  • Adriana A. Jesus
  • Alberto J. S. Duarte
  • João B. OliveiraEmail author



Immunodeficiency with hyper-IgM (HIGM) results from genetic defects in the CD40–CD40 ligand (CD40L) pathway or in the enzymes required for immunoglobulin class switch recombination and somatic hypermutation. HIGM can thus be associated with an impairment of both B-cell and T-cell activation.

Results and discussions

There are seven main subtypes of HIGM and the most frequent is X-linked HIGM, resulting from CD40L mutations. In addition to the susceptibility to recurrent and opportunistic infections, these patients are prone to autoimmune manifestations, especially hematologic abnormalities, arthritis, and inflammatory bowel disease. Furthermore, organ-specific autoantibodies are commonly found in HIGM patients.


The mechanisms by which HIGM associates to autoimmunity are not completely elucidated but a defective development of regulatory T cells, the presence of IgM autoantibodies and an impaired peripheral B-cell tolerance checkpoint have been implicated. This article reviews the main subtypes of HIGM syndrome, the clinical autoimmune manifestations found in these patients, and the possible mechanisms that would explain this association.


Autoimmunity CD40 CD40L hyper IgM inflammatory bowel disease 


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Adriana A. Jesus
    • 1
  • Alberto J. S. Duarte
    • 2
  • João B. Oliveira
    • 2
    • 3
    Email author
  1. 1.Pediatric Rheumatology Unit, Pediatrics DepartmentUniversidade de São PauloSão PauloBrazil
  2. 2.Laboratory of Medical Investigation Unit 56 (LIM-56), Dermatology DepartmentUniversidade de São PauloSão PauloBrazil
  3. 3.Research InstituteHospital do CoraçãoSão PauloBrazil

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