Collagen-specific T-cell repertoire in blood and synovial fluid varies with disease activity in early rheumatoid arthritis

Type II collagen is a DR4/DR1 restricted target of self-reactive T cells that sustain rheumatoid arthritis. The aim of the present study was to analyze the T-cell receptor repertoire at the onset of and at different phases in rheumatoid arthritis. We used the CDR3 BV-BJ spectratyping to study the response to human collagen peptide 261-273 in 12 patients with DR4+ rheumatoid arthritis (six at the onset of disease and six during the course of disease) and in five healthy DR4+ relatives. The collagen-specific T-cell repertoire is quite restricted at the onset of disease, involving approximately 10 rearrangements. Within the studied collagen-specific rearrangements, nearly 75% is shared among patients. Although the size of the repertoire used by control individuals is comparable to that of patients, it is characterized by different T-cell receptors. Part of the antigen-specific T-cell repertoire is spontaneously enriched in synovial fluid. The specific T-cell repertoire in the periphery was modulated by therapy and decreased with the remission of the disease. Failure of immunoscopy to detect this repertoire was not due to suppression of collagen-driven proliferation in vitro by CD4+ CD25+ T cells. Clinical relapse of the disease was associated with the appearance of the original collagen-specific T cells. The collagen-specific T-cell receptor repertoire in peripheral blood and synovial fluid is restricted to a limited number of rearrangements in rheumatoid arthritis. The majority of the repertoire is shared between patients with early rheumatoid arthritis and it is modulated by therapy

Axial Spondyloarthritis: Reshape the Future—From the “2022 GISEA International Symposium”

The term “axial spondyloarthritis” (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium

Arthritis in Systemic Lupus Erythematosus: From 2022 International GISEA/OEG Symposium

Musculoskeletal involvement is one of the most common manifestations of systemic lupus erythematosus (SLE), with a negative impact on both quality of life and overall prognosis. SLE arthritis can be classified into three different subtypes, with different prevalence and characteristic biomarkers and MRI findings. Identifying the pathogenetic mechanisms underlying musculoskeletal manifestations' development is crucial to develop therapeutic strategies to suppress synovial inflammation, prevent erosions and deformities, and improve SLE patients' quality of life. Hence, here we discuss the main pathogenetic mechanisms and therapeutic approaches of musculoskeletal manifestations of SLE from the 2022 International GISEA/OEG Symposium

Rheumatoid Arthritis from Easy to Complex Disease: From the "2022 GISEA International Symposium"

: Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium

Combined treatment with renin-angiotensin system blockers and polyunsaturated fatty acids in proteinuric IgA nephropathy: A randomized controlled trial

Background. Currently, several therapeutic protocols exist for IgA nephropathy (IgAN); results in slowing the progression to end-stage renal disease (ESRD) are variable, but 3c30-40% of patients require replacement therapy (dialysis or renal transplantation) by 20 years from the onset. The adverse effects brought by the chronic assumption of drugs can be a potential limit. Actually, the most used therapies for IgAN are renin-angiotensin system blockers (RASB), glucocorticoids and immunosuppressive agents. Trials with polyunsaturated fatty acids (PUFA) in IgAN have been done since the first successful attempt by Hamazaki in 1984, resulting in alternate answers, but no trials have ever been done testing the efficacy of combined therapy with RASB and PUFA. Methods. We tested the effect of a 6-month course of PUFA (3 grams/day) in a group of 30 patients with biopsy-proven IgAN and proteinuria already treated with RASB randomized to receive PUFA supplementation or to continue their standard therapy. The primary end-point was the percent reduction of proteinuria from the baseline. Secondary end-points were modifications in glomerular filtration rate (GFR), blood pressure, serum triglycerides and erythrocyturia. Results. At the end of the 6-month trial, the percent reduction of proteinuria was 72.9% in the PUFA group and 11.3% in the RASB group (P < 0.001). A reduction of 6550% of baseline proteinuria was achieved in 80.0% of PUFA patients and 20.0% of RASB patients (P = 0.002). Erythrocyturia was significantly lower in the PUFA group (P = 0.031). No significant changes in renal function, blood pressure and triglycerides were observed. Conclusions. PUFA associated with RASB reduced proteinuria in patients with IgAN more than RASB alone. \ua9 The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved

From Bench to Bedside in Rheumatoid Arthritis from the “2022 GISEA International Symposium”

While precision medicine is still a challenge in rheumatic disease, in recent years many advances have been made regarding pathogenesis, the treatment of inflammatory arthropathies, and their interaction. New insight into the role of inflammasome and synovial tissue macrophage subsets as predictors of drug response give hope for future tailored therapeutic strategies and a personalized medicine approach in inflammatory arthropathies. Here, we discuss the main pathogenetic mechanisms and therapeutic approaches towards precision medicine in rheumatoid arthritis from the 2022 International GISEA/OEG Symposium