Autoantibodies against the glial glutamate transporter GLT1/EAAT2 in Type 1 diabetes mellitus—Clues to novel immunological and non-immunological therapies

Autor: Carla Perego, Eliana S. Di Cairano, Alessandra Galli, Stefania Moretti, Elena Bazzigaluppi, Victoria Frolich Centonze, Amalia Gastaldelli, Emma Assi, Paolo Fiorina, Massimo Federici, Ottavia Porzio, Federico Bertuzzi, Alberto M. Davalli, Franco Folli
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Pharmacological Research, Vol 177, Iss , Pp 106130- (2022)
Druh dokumentu: article
ISSN: 1096-1186
DOI: 10.1016/j.phrs.2022.106130
Popis: Islet cell surface autoantibodies were previously found in subjects with type 1 diabetes mellitus (T1DM), but their target antigens and pathogenic mechanisms remain elusive. The glutamate transporter solute carrier family 1, member 2 (GLT1/EAAT2) is expressed on the membrane of pancreatic β-cells and physiologically controls extracellular glutamate concentrations thus preventing glutamate-induced β-cell death. We hypothesized that GLT1 could be an immunological target in T1DM and that autoantibodies against GLT1 could be pathogenic. Immunoprecipitation and ELISA experiments showed that sera from T1DM subjects recognized GLT1 expressed in brain, pancreatic islets, and GLT1-transfected COS7-cell extracts. We validated these findings in two cohorts of T1DM patients by quantitative immunofluorescence assays. Analysis of the combined data sets indicated the presence of autoantibodies against GLT1 in 32 of the 87 (37%) T1DM subjects and in none of healthy controls (n = 64) (p
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