PURPOSE: The risk to develop Rheumatoid Arthritis (RA) is strongly linked to HLA-DRB1*04 (DR4) and *01 (DR1). In RA, activated immune cells, as CD4+T cells, infiltrate the synovial tissue. In a previous work (1) we suggested that the collagen-specific repertoire in PBMC is modulated according to disease activity. METHODS: HLA genotyping was performed using the Innogenetics® kit, following the manufacturer’s protocol. The BV-BJ T cell receptor (TCR) analysis is described in Ria et al (1). We analyzed 100 samples from RA patients, 57 with a high disease activity (DAS > 3.7) and 43 with a low disease activity (DAS≤2.4). RESULTS: The presence of TRBV25-TRBJ2.2 and TRBV6-4-TRBJ2-3 (the two most used TCR-beta chains) in PBMC is significantly associated with disease activity in the group of DR4+ RA patients. The usage of these two receptors describes two non-overlapping groups of patients, with subjects using TRBV6-4+ displaying a significantly higher disease activity. 50% of DR4+ TRBV25- patients responded to DMARDs and the remaining responded well to biologic agents; DR4+ TRBV25+ patients failed to respond to DMARDs but displayed a good response (GR) to biologic agents. HLA-DR11 appeared highly enriched in subjects displaying a high disease activity at onset. Accordingly, within the group of DR4-, DR1- DR7- RA patients, we observed that 50% of all patients achieved a GR after DMARDs treatment; among non-responders, however, it DR11+ subjects responded less promptly than DR11- patients to biologic agents. DISCUSSION: The combination of TCR usage in DR4+ subjects and of DR haplotypes describes four distinct responses to treatment with Disease Modifying Antirheumatic Drugs (DMARDs) and biologic agents in RA patients. CONCLUSIONS: These findings show that analysis of collagen specific TCRs and HLA-DR haplotype can provide useful information for personalized treatment in RA patients. BIBLIOGRAPHY: 1. Ria F., et al. Arthr. Res. Ther., 2008.
(Collagen specific-)T cell related parameters can provide information for the management of RA patients
DI SANTE G;
2014
Abstract
PURPOSE: The risk to develop Rheumatoid Arthritis (RA) is strongly linked to HLA-DRB1*04 (DR4) and *01 (DR1). In RA, activated immune cells, as CD4+T cells, infiltrate the synovial tissue. In a previous work (1) we suggested that the collagen-specific repertoire in PBMC is modulated according to disease activity. METHODS: HLA genotyping was performed using the Innogenetics® kit, following the manufacturer’s protocol. The BV-BJ T cell receptor (TCR) analysis is described in Ria et al (1). We analyzed 100 samples from RA patients, 57 with a high disease activity (DAS > 3.7) and 43 with a low disease activity (DAS≤2.4). RESULTS: The presence of TRBV25-TRBJ2.2 and TRBV6-4-TRBJ2-3 (the two most used TCR-beta chains) in PBMC is significantly associated with disease activity in the group of DR4+ RA patients. The usage of these two receptors describes two non-overlapping groups of patients, with subjects using TRBV6-4+ displaying a significantly higher disease activity. 50% of DR4+ TRBV25- patients responded to DMARDs and the remaining responded well to biologic agents; DR4+ TRBV25+ patients failed to respond to DMARDs but displayed a good response (GR) to biologic agents. HLA-DR11 appeared highly enriched in subjects displaying a high disease activity at onset. Accordingly, within the group of DR4-, DR1- DR7- RA patients, we observed that 50% of all patients achieved a GR after DMARDs treatment; among non-responders, however, it DR11+ subjects responded less promptly than DR11- patients to biologic agents. DISCUSSION: The combination of TCR usage in DR4+ subjects and of DR haplotypes describes four distinct responses to treatment with Disease Modifying Antirheumatic Drugs (DMARDs) and biologic agents in RA patients. CONCLUSIONS: These findings show that analysis of collagen specific TCRs and HLA-DR haplotype can provide useful information for personalized treatment in RA patients. BIBLIOGRAPHY: 1. Ria F., et al. Arthr. Res. Ther., 2008.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
