Multiple sclerosis (MS) is a neuroinflammatory disease characterized by immune cell infiltration in the central nervous system and destruction of myelin sheaths. Alterations of gut bacteria abundances are present in MS patients. In mouse models of neuroinflammation, depletion of microbiota results in amelioration of symptoms, and gavage with MS patient microbiota exacerbates the disease and inflammation via Th17 cells. On the other hand, depletion of B cells using anti-CD20 is an efficient therapy in MS, and growing evidence shows an important deleterious role of B cells in MS pathology. However, the failure of TACI-Ig treatment in MS highlighted the potential regulatory role of plasma cells. The mechanism was recently demonstrated involving IgA+ plasma cells, specific for gut microbiota and producing IL-10. IgA-coated bacteria in MS patient gut exhibit also modifications. We will focus our review on IgA interactions with gut microbiota and IgA+ B cells in MS. These recent data emphasize new pathways of neuroinflammation regulation in MS.
The HLA system plays a pivotal role both in transplantation and immunology. While classical HLA genotypes matching is made at the allelic level, recent progresses were developed to explore antibody-antigen recognition by studying epitopes. Donor to recipient matching at the epitopic level is becoming a trending topic in the transplantation research field because anti-HLA antibodies are epitope-specific rather than allele-specific. Indeed, different HLA alleles often share common epitopes. We present the HLA-Epi tool (hla.univnantes.fr) to study an HLA genotype at the epitope level. Using the international HLA epitope registry (Epregistry.com.br) as a reference, we developed HLA-Epi to easily determine epitopic and allelic compatibility levels between several HLA genotypes. The epitope database covers the most common HLA alleles (N = 2976 HLA alleles), representing more than 99% of the total observed frequency of HLA alleles. The freely accessible web tool HLA-Epi calculates an epitopic mismatch load between different sets of potential recipient-donor pairs at different resolution levels. We have characterized the epitopic mismatches distribution in a cohort of more than 10,000 kidney transplanted pairs from European ancestry, which showed low number of epitopic mismatches: 56.9 incompatibilities on average. HLA-Epi allows the exploration of epitope pairing matching to better understand epitopes contribution to immune responses regulation, particularly during transplantation. This free and ready-to-use bioinformatics tool not only addresses limitations of other related tools, but also offers a cost-efficient and reproducible strategy to analyze HLA epitopes as an alternative to HLA allele compatibility. In the future, this could improve sensitization prevention for allograft allocation decisions and reduce the risk of alloreactivity.
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