Citrullination facilitates cross-reactivity of rheumatoid factor with non-IgG1 Fc epitopes in rheumatoid arthritis

Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the two most prevalent autoantibodies in rheumatoid arthritis (RA), and are thought to have distinct autoantigen targets. Whilst RF targets the Fc region of antibodies, ACPAs target a far broader spectrum of citrullinated peptides. Here we demonstrate significant sequence and structural homology between proposed RF target epitopes in IgG1 Fc and the ACPA target fibrinogen. Two of the three homologous sequences were susceptible to citrullination, and this modification, which occurs extensively in RA, permitted significant cross-reactivity of RF+ patient sera with fibrinogen in both western blots and ELISAs. Crucially, this reactivity was specific to RF as it was absent in RF− patient and healthy control sera, and could be inhibited by pre-incubation with IgG1 Fc. These studies establish fibrinogen as a common target for both RF and ACPAs, and suggest a new mechanism in RF-mediated autoimmune diseases wherein RF may act as a precursor from which the ACPA response evolves

Management of Peripheral Arthritis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations

Prevalence of periprosthetic osteolysis after total hip replacement in patients with rheumatic diseases

Rodolfo Perez Alamino, Carolina Casellini, Andrea Banos, Emilce Edith Schneeberger, Susana Alicia Gagliardi, José Antonio Maldonado Cocco, Gustavo CiteraSection of Rheumatology, Instituto de Rehabilitación Psicofísica, Buenos Aires, ArgentinaAbstract: Periprosthetic osteolysis (PO) is a frequent complication in patients with joint implants. There are no data regarding the prevalence of PO in patients with rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), ankylosing spondylitis (AS), and osteoarthritis (OA).Objectives: To evaluate the prevalence of PO in patients with RA, JCA, AS, and OA, who have undergone total hip replacement (THR), and to identify factors associated with its development.Methods: The study included patients diagnosed with RA (ACR 1987), AS (modified New York criteria), JCA (European 1977 criteria), and osteoarthritis (OA) (ACR 1990 criteria) with unilateral or bilateral THR. Demographic, clinical, and therapeutic data were collected. Panoramic pelvic plain radiographs were performed, to determine the presence of PO at acetabular and femoral levels. Images were read by two independent observers.Results: One hundred twenty-two hip prostheses were analyzed (74 cemented, 30 cementless, and 18 hybrids). The average time from prosthesis implantation to pelvic radiograph was comparable among groups. PO was observed in 72 hips (59%). In 55% of cases, PO was detected on the femoral component, with a lower prevalence in RA (53%) vs AS (64.7%) and JCA (76.5%). Acetabular PO was more frequent in JCA patients (58.8%), compared with RA (11.6%) and OA (28.5%) patients (P = 0.0001 and P = 0.06, respectively). There was no significant association between the presence of PO and clinical, functional, or therapeutic features.Conclusion: The prevalence of PO was 59%, being more frequent at the femoral level. Larger studies must be carried out to determine the clinical significance of radiologic PO.Keywords: periprosthetic osteolysis, hip prosthesis, rheumatoid arthritis, juvenile chronic arthritis, ankylosing spondyliti

Trends in Time to Diagnosis in Spondyloarthritis Patients. Association with 2009 ASAS Classification Criteria and Clinical Presentation at Disease Onset. Data from Comospa Study

Pathophysiology and treatment of rheumatic disease

ASAS CONSENSUS DEFINITION OF EARLY AXIAL SPONDYLOARTHRITIS

Navarro-Compán V, Benavent D, Capelusnik D, et al. ASAS CONSENSUS DEFINITION OF EARLY AXIAL SPONDYLOARTHRITIS. Annals of the Rheumatic Diseases. 2023;82(Suppl. 1):35-36