Pröbstel A, Zhou X, Baumann R, Wischnewski S, Kutza M, Rosa L, Sellrie K, Bischof A, Kim K, Ramesh A, Dandekar R, Greenfield A, Schubert R, Bisanz J, Vistnes S, Khaleghi K, Landefeld J, Kirkish G, Liesche-Starnecker F, Ramaglia V, Singh S, Tran E, Barba P, Zorn K, Oechtering J, Forsberg K, Shiow L, Henry R, Graves J, Cree B, Hauser S, Kuhle J, Gelfand J, Andersen P, Schlegel J, Turnbaugh P, Seeberger P, Gommerman J, Wilson M, Schirmer L, Sergio P, Baranzini E (2020) Science Immunology Vol. 5, Issue 53, eabc7191 DOI: 10.1126/sciimmunol.abc7191
Multiple sclerosis (MS) is associated with production of oligoclonal IgG antibodies within the central nervous system (CNS), but less is known about the status of IgA-producing cells. Pröbstel et al. detected clonally expanded IgA+ cells in cerebrospinal fluid and tissue adjacent to areas of active MS-associated demyelination.
Recombinant IgA antibodies assembled from the cloned antibody genes bound to surface antigens found on multiple bacterial phyla but did not cross-react with brain tissue. Recruitment of gut-associated IgA+ B cells and plasma cells to the CNS is a potential biomarker of disease activity in MS.
The arrival of these cells in the CNS may reflect recruitment of a homeostatic set of regulatory cells from the gut that have the capacity to dampen excessive inflammation.