Research Article

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

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Science  27 Sep 2019:
Vol. 365, Issue 6460, eaav7188
DOI: 10.1126/science.aav7188

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  • RE: IgG Heavy Chain Genes and Susceptibility to Multiple Sclerosis
    • Janardan Pandey, Professor of Microbiology and Immunology, Medical University of South Carolina

    The members of the International Multiple Sclerosis Genetics Consortium, in their paper on human genomics, “Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility” (27 September, p. eaav7188), have identified several hundred MS susceptibility genes as well as the cell populations that are enriched for these genes. The enriched cell populations include B cells, which are major players in the adaptive immune system. In MS IgG-expressing B cells cross the blood brain barrier, are involved in the pathophysiology of the disease (1) and, as the authors point out, are relevant to “effective B cell-directed therapies in MS” (2). Therefore, identification of the genes expressed in B cells is of paramount importance for understanding the autoimmune mechanisms involved and for devising immunotherapeutic approaches to conquer this disabling disease.
    Given the massive genomic undertaking by the MS Consortium, one might assume that all B cell enriched genes, especially those relevant to MS pathogenesis, must have been evaluated in this study. However, this is probably not the case. In the materials and methods section of their article, the authors state, “we analyzed genetic data from 15 GWASs of MS”. The GWASs do not evaluate/impute the genes that encode the 18 GM (gamma marker) allotypes, although the majority of the GM alleles are common, some with a frequency of > 70% (3). Additionally, the customized genotyping chips used in this...

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    Competing Interests: None declared.

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