Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-? are targets of the autoimmune response in type 1 diabetes

Type 1 diabetes (T1D) results from the destruction of pancreatic beta-cells by the immune system, and CD8(+) T lymphocytes are critical actors in this autoimmune response. Pancreatic islets are surrounded by a mesh of nervous cells, the peri-insular Schwann cells, which are also targeted by autoreactive T lymphocytes and express specific antigens, such as the neurotrophic factor S100-beta. Previous work has shown increased proliferative responses to whole S100-beta in both human T1D patients and the nonobese diabetic (NOD) mouse model. We describe for the first time naturally processed and presented epitopes (NPPEs) presented by class I human leukocyte antigen-A*02:01 (A2.1) molecules derived from S100-beta. These NPPEs triggered IFN-gamma responses more frequently in both newly diagnosed and long-term T1D patients compared with healthy donors. Furthermore, the same NPPEs are recognized during the autoimmune response leading to diabetes in A2.1-transgenic NOD mice as early as 4 wk of age. Interestingly, when these NPPEs are used to prevent diabetes in this animal model, an acceleration of the disease is observed together with an exacerbation in insulitis and an increase in S100-beta-specific cytotoxicity in vaccinated animals. Whether these can be used in diabetes prevention needs to be carefully evaluated in animal models before use in future clinical assays.-Calvino-Sampedro, C., Gomez-Tourino, I., Cordero, O. J., Reche, P. A., Gomez-Perosanz, M., Sanchez-Trincado, J. L., Rodriguez, M. A., Sueiro, A. M., Vinuela, J. E., Calvino, R. V. Naturally presented HLA class I-restricted epitopes from the neurotrophic factor S100-beta are targets of the autoimmune response in type 1 diabetes

Influence of the STAT3 genetic variants in the susceptibility to psoriatic arthritis and Behcet's disease

Pathophysiology and treatment of rheumatic disease

Patient Global Assessment in Psoriatic Arthritis: A Multicenter GRAPPA and OMERACT Study

Objective. During OMERACT 8, delegates selected patient global assessment (PGA) of disease as a domain to be evaluated in randomized controlled trials in psoriatic arthritis (PsA). This study assessed the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional utility of separate VAS scales for joints (PJA) and skin (PSA). Methods. In total, 319 consecutive patients with PsA (186 men, 133 women, mean age 51 +/- 13 yrs) were enrolled. PGA, PJA, and PSA were administered at enrolment (WO) and after 1 week (WI). Detailed clinical data, including ACR joint count, Psoriasis Area and Severity Index (PASI), and Hospital Anxiety and Depression Scale, were recorded. Results. Comparison of WO and WI scores showed no significant variations (intraclass correlation coefficients for PGA 0.87, PJA 0.86, PSA 0.78), demonstrating the reliability of the instrument. PGA scores were not influenced by patient anxiety or depression, but were dependent on PJA and PSA (p = 0.00001). PJA was dependent on the number of swollen and tender joints (p < 0.00001). PSA scores were influenced by the extent of skin psoriasis and by hand skin involvement (p = 0.00001). Joint and skin disease were found not to correlate in terms of disease activity as evidenced by the swollen joint count compared to PASI (r = 0.11) and by the PJA compared to PSA (r = 0.38). Conclusion. PGA assessed by means of VAS is a reliable tool related to joint and skin disease activity. Because joint and skin disease often diverge it is suggested that in some circumstances both PJA and PSA are also assessed. (First Release Feb 15 2011; J Rheumatol 201138:898-903; doi:10.3899/jrheum.100857