Human FOXP3 blocking peptide

Background & objectives: Cells and cell proportions may indicate the equilibrium status of the immune system. The present study was conducted to evaluate the role of cytokines and the immunocompetent cells as biomarkers of remission in rheumatoid arthritis (RA) patients intended to withdraw or reduce disease-modifying anti-rheumatic drug (DMARD) treatment. Methods: This prospective observational study involved newly diagnosed and treated RA patients who fulfilled 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. The patients were classified based on disease activity score (DAS)28-C-reactive protein (CRP)(3) score into remission (<= 2.6) and treatment-naive/active (>2.6) groups. Remission patients were followed up for six months and were reclassified into those in sustained remission (<= 2.6) and relapse (>2.6) based on the DAS28-CRP(3) score. Various cytokines and cell surface markers were quantitated using whole blood samples, and the CD3+/CD19+ and FOXP3+/CD4+ ratios were calculated. The clinical, demographic, cytokine and cellular phenotype characteristics were compared between remission and treatment-naive groups. The factors associated with sustained remission were verified. Results: Of the 72 patients, 52 were in remission and 20 were DMARD naive and had active disease. Duration of illness, interleukin-6 (IL-6) and IL-10 were significantly different between remission and treatment naive/active disease patients. Increased likelihood for achieving sustained remission was noted in RA patients with baseline NLR <= 2. Other demographic/clinical variables and cell phenotypes, namely age, gender, duration of illness, CD3+, CD4+, FOXP3+, CD19+, CD3+/CD19+, FOXP3+/CD4+ and cytokines - IL-6 and IL-10 were not associated with sustained remission. Interpretation & conclusions: The present preliminary study highlighted the potential of NLR in predicting sustained remission in RA patients with a cut-off <2. Further study with a large sample size should be done to confirm this finding.

It is a central tenet of the clonal selection theory, that lymphocyte repertoires are tolerized to self-antigens during their ontogeny. Germinal centres are the sites in secondary lymphoid tissues where B cells undergo affinity maturation and class-switching to produce high-affinity antibodies. This process is crucial, both in our ability to mount protective humoral responses to infections and to vaccinations, but it is also involved in untoward reactions to self-antigens, which underlie autoimmunity. The process of affinity maturation poses a significant challenge to tolerance, as the random nature of somatic hypermutation can introduce novel reactivities. Therefore, it has been a long-standing idea that mechanisms must exist which limit the emergence of autoreactivity at the germinal centre level. One of these mechanisms is the requirement for linked recognition, which imposes on B cells a dependence on centrally tolerant T follicular helper cells. However, as linked recognition can be bypassed by adduct formation of autoantigenic complexes, it has been an appealing notion that there should be an additional layer of dominant mechanisms regulating emergence of autoreactive specificities. About a decade ago, this notion was addressed by the discovery of a novel subset of T regulatory cells localizing to the germinal centre and regulating germinal centre B-cell responses. Here, we detail the progress that has been made towards characterizing this T follicular regulatory cell subset and understanding the functions of these 'guardians of the germinal centre'.