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Comprehensive review of autoantibodies in patients with hyper-IgM syndrome

Cellular & Molecular Immunology volume 15, pages 610–617 (2018)Cite this article

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.

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Authors and Affiliations

  1. Laboratory of Immunology, Institute Pasteur de Tunis and Faculty of Medicine, University Tunis El Manar, Tunis, 1002, Tunisia

    Mohamed-Ridha Barbouche, Imen Ben-Mustapha & Nourhen Agrebi

  2. Humanitas Clinical and Research Center, Rozzano, 20089, Italy

    Qubo Chen, Haiyan Zhang & Pietro Invernizzi

  3. Clinical Laboratory, Guangdong Provincial Hospital of Chinese medicine, Guangzhou, 510000, China

    Qubo Chen

  4. Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Monza (MB), 20900, Italy

    Marco Carbone, Federica Malinverno, Francesca Bernuzzi, Haiyan Zhang & Pietro Invernizzi

  5. Department of Research and Development, Inova Diagnostics, San Diego, 92131, USA, CA

    Zakera Shums & Gary L Norman

  6. Department of Anesthesia and Intensive Care, Children Hospital Bechir Hamza, Tunis and Faculty of Medicine, University Tunis El Manar, Tunis, 1007, Tunisia

    Mehdi Trifa

  7. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State, Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 200001, Shanghai, China

    Haiyan Zhang

  8. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, 95616, USA, CA

    Christopher Chang & M Eric Gershwin

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  1. Mohamed-Ridha Barbouche
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  2. Qubo Chen
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  4. Imen Ben-Mustapha
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  11. Gary L Norman
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  14. Pietro Invernizzi
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Correspondence to Pietro Invernizzi.

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Barbouche, MR., Chen, Q., Carbone, M. et al. Comprehensive review of autoantibodies in patients with hyper-IgM syndrome. Cell Mol Immunol 15, 610–617 (2018). https://doi.org/10.1038/cmi.2017.140

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