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Autoantibodies, Polymorphisms in the Serotonin Pathway, and Human Leukocyte Antigen Class II Alleles in Chronic Fatigue Syndrome

Are They Associated with Age at Onset and Specific Symptoms?

Authors

  • Oscar-Danilo Ortega-Hernandez,

    1. Department of Medicine “B” and Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Mariaclara Cuccia,

    1. Department of Genetics and Microbiology – Immunogenetics Laboratory, University of Pavia, Pavia, Italy
    2. Interdepartmental Center of Gender Studies, University of Pavia, Pavia, Italy
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  • Sara Bozzini,

    1. Department of Genetics and Microbiology – Immunogenetics Laboratory, University of Pavia, Pavia, Italy
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  • Nicola Bassi,

    1. Department of Rheumatology, University of Padova, Padova, Italy
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  • Samuel Moscavitch,

    1. Department of Medicine “B” and Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Lina-Marcela Diaz-Gallo,

    1. Cellular Biology and Immunogenetics Unit, Corporaciòn para Investigaciones Biològicas, Medellìn, Columbia
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  • Miri Blank,

    1. Department of Medicine “B” and Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Nancy Agmon-Levin,

    1. Department of Medicine “B” and Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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  • Yehuda Shoenfeld

    1. Department of Medicine “B” and Center for Autoimmune Diseases, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    2. Incumbent of the Laura Schwarz-Kip Chair for Autoimmunity, Tel-Aviv University, Tel-Aviv, Israel
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Address for correspondence: Yehuda Shoenfeld, M.D., F.R.C.P., Department of Medicine “B,” Sheba Medical Center, Tel Hashomer 52621, Israel. Voice: +972 3 5302652; fax +972 3 5352855. Shoenfel@post.tau.ac.il

Abstract

This study aimed to determine the influence of autoantibodies, polymorphisms in the serotonin pathway, and human leukocyte antigen (HLA) class II genes on age at chronic fatigue syndrome (CFS) onset and symptoms. Eighty-one CFS patients were enrolled, and clinical data were recorded. Autoantibodies to different components of the central nervous system were tested. Polymorphisms in the promoter of the serotonin transporter gene (l/s) and a single nucleotide polymorphism in the serotonin receptor-2A gene (A/G) as well as HLA class II alleles were determined. Multivariate logistic-regression analyses were carried out. The mean age at CFS onset ± SD was 33.5 ± 12.5 years. An age at CFS onset (ACFSO) during the third decade of life was associated with the serotonin receptor AA genotype and the HLA-DRB1*03 allele. An ACFSO during the fourth decade of life was associated with the HLA-DRB1*07 allele, whereas an ACFSO ≥ 43 years was associated with having at least one copy of the serotonin G allele. Concerning CFS symptoms, the serotonin AG genotype was protective against depressive symptoms. Although having at least one copy of the serotonin A allele and being female were associated with risk for arthralgia, the presence of antineuronal cell antibodies was protective against this. Episodes of unexplained fever were associated with the HLA-DRB1*11 allele. None of the genetic or serological features was associated with myalgia. None of the antibodies determined correlated with any ACFSO or other symptoms. Our results reveal that in CFS, like other autoimmune diseases, different genetic features are related to age at CFS onset and symptoms.

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