title: The dimeric form of HLA-G molecule is associated with the response of early rheumatoid arthritis (ERA) patients to methotrexate.
abstract: A growing body of evidence indicates a possible involvement of HLA (human leukocyte antigen)-G antigens in rheumatoid arthritis (RA), mainly in the HLA-G dimeric isoform, the most active HLA-G form with the strongest immunosuppression, that showed an excellent anti-inflammatory effect in collagen-induced arthritis model mice. However, the relevance of HLA-G dimers in RA response to methotrexate (MTX) treatment is still unknown. We analyzed the HLA-G dimers' amount in plasma samples from early rheumatoid arthritis (ERA) patients before MTX therapy and evaluated the role of these molecules as biomarker of the different response to the treatment. Plasma sHLA-G levels were detected by ELISA, and HLA-G dimeric and monomeric forms were revealed by Western blot in 12 MTX responder (reaching DAS28 remission <2.6) and 8 MTX non-responder (DAS28 ≥5.1) patients before the therapy. The response to MTX was evaluated after 6 months of treatment. All ERA patients reaching remission showed higher plasma sHLA-G levels and the 78 kDa HLA-G dimeric form. Unresponsive ERA patients were characterized by lower plasma sHLA-G levels, and only one patient presented the 78 kDa HLA-G dimeric form (DAS28 5.1). Our preliminary results support the hypothesis that in ERA patients, sHLA-G and, in particular, the presence of the dimeric form in plasma samples before MTX therapy could be an a priori biomarker for the response to MTX treatment.
authors: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Via Luigi Borsari, 46 44121, Ferrara, Italy. rbr@unife.it.
authors: Roberta
authors: R
authors: Rizzo
authors: Section of Haematology and Rheumatology, University of Ferrara, Ferrara, Italy.
authors: Ilaria
authors: I
authors: Farina
authors: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Via Luigi Borsari, 46 44121, Ferrara, Italy.
authors: Daria
authors: D
authors: Bortolotti
authors: Section of Haematology and Rheumatology, University of Ferrara, Ferrara, Italy.
authors: Elisa
authors: E
authors: Galuppi
authors: Section of Haematology and Rheumatology, University of Ferrara, Ferrara, Italy.
authors: Melissa
authors: M
authors: Padovan
authors: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, Via Luigi Borsari, 46 44121, Ferrara, Italy.
authors: Dario
authors: D
authors: Di Luca
authors: Section of Haematology and Rheumatology, University of Ferrara, Ferrara, Italy.
authors: Marcello
authors: M
authors: Govoni
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D059951:HLA-G Antigens / Q000097:blood*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D059951:HLA-G Antigens; D008727:Methotrexate
keywords: Disease-modifying anti-rheumatic drugs; Early rheumatoid arthritis; Human leukocyte antigen-G; Methotrexate