Multiple Types of Autoimmunity Resulting from the same CD40 Ligand Mutation

Document Type: Original Article


Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children Medical Center, Tehran University of Medical Science, Tehran, Iran


Background/Objectives: Hyper-immunoglobulin M (HIgM) syndrome is a primary immunodeficiency disease in which impaired immunoglobulin class-switch recombination causes normal or high levels of serum IgM versus low or undetectable serum levels of class-switched immunoglobulins.
Methods: The diagnoses of all patients with HIgM in familial cases were evaluated based on genetic testing. Since this syndrome can present with either infectious diseases, malignancies, or autoimmune diseases, all medical complications were recorded in the index patients and relatives.
Results: Surprisingly, the evaluation identified a family with 3 males suffering from CD40 ligand deficiency, and each one had different autoimmune manifestations, including Guillain-barre syndrome and pauciarticular and polyarticular juvenile rheumatoid arthritis.
Conclusions: Based on the results, it is hypothesized that other genetic modifying factors or environmental parameters affecting epigenetics may have a significant role in the presentation of autoimmunity in CD40 ligand deficiency.