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Low T‐cell receptor (TCR)/CD28 signaling lymphocytes are expanded in arthritis. We asked whether the down‐expression of TCR‐related molecules correlates with specific arthritis characteristics and if it has clinical implications. TCR‐ZETA, ZAP‐70 and CD28 expression was measured by flow cytometry in synovial fluid (SF) and peripheral blood (PB)‐derived T cells. In PB, ZETA‐downregulation in CD4+CD28+ and consequent CD4+CD28lowZETAlow cell expansion correlate with CRP elevation, leukocyte recruitment into SF and, primarily, disease activity (DAS). In some patients, ZETA‐downregulation extends to CD8+CD28null and/or CD8+CD28+ cells, and this correlates with enhanced leukocyte recruitment, multiple joint involvement, and disability index (HAQ). ZETA‐downregulation in CD4+CD28+ may also lead to CD4+CD28+ZETAnull cell expansion, which strongly correlates with HAQ. In SF, ZETA‐downregulation in CD8+CD28null and consequent CD8+CD28nullZETAlow/null cell expansion correlate with CRP elevation and neutrophilic influx into SF, whereas ZAP‐downregulation in CD8+CD28+ and consequent CD8+CD28lowZAPlow cell expansion strongly correlate with HAQ and DAS. ZETA‐downregulation is preponderant in SF of seronegative arthritides, with seronegative rheumatoid arthritis showing significant down‐regulation in CD8+CD28null, and non‐rheumatoid arthritides showing significant down‐regulation in CD4+CD28+. Altogether, we identified new molecular and cellular biomarkers of arthritis‐related T‐cell inflammation, useful for assessing arthritis activity, predicting polyarticular progression and functional impairment, characterizing seronegative arthritides, and possibly tailoring immunotherapies. [ABSTRACT FROM AUTHOR]

Background Alterations of B cell subset distribution have been described in the peripheral blood (PB) of rheumatoid arthritis (RA) patients, but no data are available on differences between the onset and the established phases of the disease. The purpose of the study was to clarify whether a peculiar distribution of B cell subsets characterizes RA onset, thus leading to a more favorable clinical response to treatment, and to evaluate the possible association of a particular B cell subpopulation with response to therapy. Results 122 RA patients were enrolled: 25 had symptom duration less than 3 months and were defined as having "very early RA" (VERA), and 43 had symptom duration from more than 3 months up to one year (early-RA: ERA). The other 54 RA patients had long-standing RA (LSRA). At baseline and at 6-month follow-up visit peripheral blood samples were collected and analyzed by flow cytometry for the distribution of circulating B cell subsets by staining with surface markers CD45, CD19, CD38, CD27 and IgD and intracellular marker ZAP70. VERA and ERA patients showed higher percentages and absolute counts of circulating antigen inexperienced naïve B cells (IgD + CD27-) and lower percentages and absolute numbers of double negative (IgD-CD27-) memory B cells and plasmablasts (CD38 + CD27+) compared to LSRA patients. At the multivariate analysis, a higher frequency of naïve B cells (IgD + CD27-) at baseline arose as significant predictor of CDAI remission, together with "having VERA disease" and a low disease activity at baseline. Conclusions The onset of RA is characterized by higher percentages and absolute numbers of naïve B cells and lower numbers of plasmablasts and double negative memory B cells compared to established RA. Naïve B cells could represent a promising biomarker of outcome. [ABSTRACT FROM AUTHOR]

Multidisciplinary team (MDT) discussion is the gold standard in the management of interstitial lung disease (ILD). The rheumatologist is not routinely involved in MDT, even if up to 20% of ILD are related to systemic autoimmune rheumatic diseases (SARD). The study aims to assess the agreement and its variation over time between rheumatologists and pulmonologists in the screening of SARD and between rheumatologists and an MDT extended to rheumatologists (eMDT) in evaluating the progression of SARD. We computed the agreement between the pulmonologist and rheumatologist in the identification of red flags for SARDs of 81 ILD cases and between the rheumatologist alone and eMDT in the confirmation of 70 suspected SARD-ILD progressions. The agreement between rheumatologists and pulmonologists was moderate for the detection of autoimmunity test positivity (κ = 0.475, p < 0.001) and family history of SARD (κ = 0.491, p < 0.001) and fair for the identification of extrapulmonary symptoms (κ = 0.225, p = 0.064) or routine laboratory abnormalities consistent with SARD. The average agreement between the rheumatologist and eMDT in the identification of ILD progression was moderate (κ = 0.436, p < 0.001). The class of agreement improved from the first to the third semester. The average agreement with the rheumatologist ranged from fair to moderate, suggesting that a shared evaluation of SARD-ILD in eMDT could improve the diagnostic work-up and the evaluation of ILD progression. [ABSTRACT FROM AUTHOR]