{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:35:41Z","timestamp":1777372541223,"version":"3.51.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T00:00:00Z","timestamp":1557360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003336","name":"National Science Fund, Bulgaria","doi-asserted-by":"crossref","award":["DH03\/11\/2016"],"award-info":[{"award-number":["DH03\/11\/2016"]}],"id":[{"id":"10.13039\/501100003336","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,14]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Type 1 diabetes mellitus is an autoimmune metabolic disorder characterized by chronic hyperglycemia, the presence of autoreactive T and B cells and autoantibodies against self-antigens. A membrane-bound enzyme on the pancreatic beta-cells, glutamic acid decarboxylase 65 (GAD65), is one of the main autoantigens in type 1 diabetes. Autoantibodies against GAD65 are potentially involved in beta-cell destruction and decline of pancreatic functions. The human complement receptor type 1 (CD35) on B and T lymphocytes has a suppressive activity on these cells. We hypothesized that it may be possible to eliminate GAD65-specific B cells from type 1 diabetes patients by using chimeric molecules, containing an anti-CD35 antibody, coupled to peptides resembling GAD65 B\/T epitopes. These molecules are expected to selectively bind the anti-GAD65 specific B cells by the co-cross-linking of the immunoglobulin receptor and CD35 and to deliver a suppressive signal. Two synthetic peptides derived from GAD65 protein (GAD65 epitopes) and anti-CD35 monoclonal antibody were used for the construction of two chimeras. The immunomodulatory activity of the engineered antibodies was tested in vitro using peripheral blood mononuclear cells (PBMCs) from type 1 diabetes patients. A reduction in the number of anti-GAD65 IgG antibody-secreting plasma cells and increased percentage of apoptotic B lymphocytes was observed after treatment of these PBMCs with the engineered antibodies. The constructed chimeric molecules are able to selectively modulate the activity of GAD65-specific B lymphocytes and the production of anti-GAD65 IgG autoantibodies by co-cross-linking of the inhibitory CD35 and the B cell antigen receptor (BCR). This treatment presents a possible way to alter the autoimmune nature of these cells.<\/jats:p>","DOI":"10.1111\/cei.13305","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T14:18:31Z","timestamp":1555942711000},"page":"329-340","source":"Crossref","is-referenced-by-count":7,"title":["Protein-engineered molecules carrying GAD65 epitopes and targeting CD35 selectively down-modulate disease-associated human B lymphocytes"],"prefix":"10.1093","volume":"197","author":[{"given":"I K","family":"Manoylov","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G V","family":"Boneva","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I A","family":"Doytchinova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N M","family":"Mihaylova","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9161-3325","authenticated-orcid":false,"given":"A I","family":"Tchorbanov","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria"},{"name":"National Institute of Immunology, Sofia, 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