Comprehensive review of autoantibodies in patients with hyper-IgM syndrome.

Abstract

Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene. The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis. In the present study, we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome. Serum, liver-related and liver-not-related autoantibodies IgG, IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients (8 males and 5 females, aged 1-12 years) with hyper-immunoglobulin M syndrome during 1995-2012 and, as controls, 21 age- and gender-matched blood donors. The level of IgM antibody against MIT3 was significantly higher in patients than in controls (35.8 vs 10.7, P=0.002). Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls (P<0.0001). Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05% of controls. By immunofluorescence, 92.3% of patients were MIT3 IgM positive vs none of the controls. In conclusion, the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M syndrome. The presence of the hallmark of primary biliary cholangitis, a disease where the CD40 ligand is a key player, in an immunodeficiency disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis.

• Authors: Mohamed-Ridha Barbouche, Qubo Chen, Marco Carbone, Imen Ben-Mustapha, Zakera Shums, Mehdi Trifa, Federica Malinverno, Francesca Bernuzzi, Haiyan Zhang, Nourhen Agrebi, Gary L Norman, Christopher Chang, M Eric Gershwin, Pietro Invernizzi
• Journal: Cellular & molecular immunology (Cell Mol Immunol) Vol. 15 Issue 6 Pg. 610-617 (06 2018) ISSN: 2042-0226 [Electronic] China
• PMID: 29400703 (Publication Type: Journal Article, Review)

Chemical References

• Autoantibodies

Topics

• Autoantibodies (blood, immunology)
• Case-Control Studies
• Cell Line
• Child
• Child, Preschool
• Female
• Humans
• Hyper-IgM Immunodeficiency Syndrome (blood, immunology)
• Infant
• Liver (metabolism)
• Male