THU0151 COMPARISON BETWEEN THREE PROPOSED DEFINTIONS OF DIFFICULT-TO-TREAT/REFRACTORY RHEUMATOID ARTHRITIS IN A COHORT OF BDMARD-TREATED PATIENTS

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Calprotectin in rheumatic diseases

none7Calprotectin is a heterodimer formed by two proteins, S100A8 and S100A9, which are mainly produced by activated monocytes and neutrophils in the circulation and in inflamed tissues. The implication of calprotectin in the inflammatory process has already been demonstrated, but its role in the pathogenesis, diagnosis, and monitoring of rheumatic diseases has gained great attention in recent years. Calprotectin, being stable at room temperature, is a candidate biomarker for the follow-up of disease activity in many autoimmune disorders, where it can predict response to treatment or disease relapse. There is evidence that a number of immunomodulators, including TNF-α inhibitors, may reduce calprotectin expression. S100A8 and S100A9 have a potential role as a target of treatment in murine models of autoimmune disorders, since the direct or indirect blockade of these proteins results in amelioration of the disease process. In this review, we will go over the biologic functions of calprotectin which might be involved in the etiology of rheumatic disorders. We will also report evidence of its potential use as a disease biomarker.noneOmetto, Francesca; Friso, Lara; Astorri, Davide; Botsios, Costantino; Raffeiner, Bernd; Punzi, Leonardo; Doria, AndreaOmetto, Francesca; Friso, Lara; Astorri, Davide; Botsios, Costantino; Raffeiner, Bernd; Punzi, Leonardo; Doria, Andre

An ultrasonographic study of enthesis in early psoriatic arthritis patients naive to traditional and biologic DMARDs treatment

The aim of this study was to evaluate the rate of power Doppler ultrasound (PDUS) abnormalities at entheseal sites in patients with early psoriatic arthritis (PsA) naïve to traditional and biologic DMARDs and to compare the PDUS findings with clinical examination. PsA patients with early disease and naïve to traditional and biologic DMARDs were consecutively enrolled in this study. Patients underwent PDUS examination of the following bilateral entheseal sites: common extensor tendon at its insertion at the lateral humeral epicondyle; quadriceps tendon at its insertion at the superior pole of the patella; patellar tendon at its insertion at the tibial tuberosity; medial collateral ligament at its proximal insertion and Achilles tendon at its insertion at the calcaneus. The Leeds enthesitis index (LEI) was used to assess clinical entheseal involvement. Twenty-one early PsA patients completed the clinical and PDUS examinations. Clinical entheseal involvement was found in 9 (42.9 %) and PDUS abnormalities in 20 (95.5 %) of the 21 early PsA patients. Achilles tendon insertion was the site with the major entheseal abnormalities. Active (power Doppler positive) entheseal lesions were found in 4.7, 9.5, 14.3 and 14.3 % of patients at the lateral humeral epicondyle; quadriceps tendon, patellar tendon insertions, and Achilles tendon insertions, respectively. Concordance between clinical (LEI) and PDUS was poor. The present study confirms that PDUS allows detecting structural and inflammatory abnormalities of enthesis in early PsA patients. Our study shows that, in early disease, active abnormalities seem to have a low prevalence

Islet Transplantation Is Associated With an Improvement of Cardiovascular Function in Type 1 Diabetic Kidney Transplant Patients

OBJECTIVE—Cardiovascular mortality and morbidity are major problems in type 1 diabetic patients with end-stage renal disease (ESRD). The aim of this study was to determine whether islet transplantation can improve cardiovascular function in these patients. RESEARCH DESIGN AND METHODS—We assessed various markers of cardiac function at baseline and 3 years later in a population of 42 type 1 diabetic patients with ESRD who received a kidney transplant. Seventeen patients then received an islet transplant that had persistent function as defined by long-term C-peptide secretion (kidney-islet group). Twenty-five patients did not receive a functioning islet transplant (kidney-only group). RESULTS—GHb levels were similar in the two groups, whereas the exogenous insulin requirement was lower in the kidney-islet group with persistent C-peptide secretion. Overall, cardiovascular parameters improved in the kidney-islet group, but not in the kidney-only group, with an improvement of ejection fraction (from 68.2 ± 3.5% at baseline to 74.9 ± 2.1% at 3 years posttransplantation, P < 0.05) and peak filling rate in end-diastolic volume (EDV) per second (from 3.87 ± 0.25 to 4.20 ± 0.37 EDV/s, P < 0.05). Time to peak filling rate remained stable in the kidney-islet group but worsened in the kidney-only group (P < 0.05). The kidney-islet group also showed a reduction of both QT dispersion (53.5 ± 4.9 to 44.6 ± 2.9 ms, P < 0.05) and corrected QT (QTc) dispersion (67.3 ± 8.3 to 57.2 ± 4.6 ms, P < 0.05) with higher erythrocytes Na+-K+-ATPase activity. In the kidney-islet group only, both atrial natriuretic peptide and brain natriuretic peptide levels decreased during the follow-up, with a stabilization of intima-media thickness. CONCLUSIONS—Our study showed that type 1 diabetic ESRD patients receiving a kidney transplant and a functioning islet transplant showed an improvement of cardiovascular function for up to 3 years of follow-up compared with the kidney-only group, who experienced an early failure of the islet graft or did not receive an islet graft

Early characterization of difficult-to-treat rheumatoid arthritis by suboptimal initial management: a multicentre cohort study

Objectives To demonstrate that unsuccessful treatment optimization in early disease is associated with difficult-to-treat RA (D2T-RA). Methods In this retrospective multicentre cohort study conducted from 09/2021-03/2022, we enrolled individuals fulfilling the 2010 ACR/EULAR RA criteria diagnosed 2000-2019. The outcome was D2T-RA by the EULAR definition. We used robust regression to examine the associations with delay, dose, duration of methotrexate and discontinuation of glucocorticoids. We tested through multinomial regression which factors were associated with persistent inflammatory refractory RA (PIRRA) or non-inflammatory refractory RA (NIRRA). Sensitivity analysis included a case-control study matching the year of diagnosis. Results We enrolled 48 D2T-RA patients and 145 non-D2T-RA controls. Methotrexate was started within 3 months in 16.7% of D2T-RA vs 33.1% of non-D2T-RA (P = 0.011). Adequate duration of methotrexate was obtained in significantly fewer D2T-RA patients (70.8% vs 85.5%). Glucocorticoids were continued beyond 6 months in a higher proportion of D2T-RA patients (70.8% vs 33.8%, P < 0.001). In multiple regression, treatment delay beyond 3 months (OR 0.3; 95% CI 0.1, 0.9) and non-discontinuation of glucocorticoids after 6 months (OR 4.6; 95% CI 2.2, 9.5) were significantly associated with D2T-RA. Treatment delay was significantly associated with PIRRA only, while non-discontinuation of glucocorticoids was significantly associated with PIRRA and NIRRA. Results were replicated in sensitivity analyses. Conclusion Failure to start methotrexate within 3 months and not being off glucocorticoids within 6 months are early predictive features of D2T-RA

Unique expansion of IL-21+ Tfh and Tph cells under control of ICOS identifies Sjögren's syndrome with ectopic germinal centres and MALT lymphoma.

OBJECTIVES To explore the relevance of T-follicular-helper (Tfh) and pathogenic peripheral-helper T-cells (Tph) in promoting ectopic lymphoid structures (ELS) and B-cell mucosa-associated lymphoid tissue (MALT) lymphomas (MALT-L) in Sjögren's syndrome (SS) patients. METHODS Salivary gland (SG) biopsies with matched peripheral blood were collected from four centres across the European Union. Transcriptomic (microarray and quantitative PCR) analysis, FACS T-cell immunophenotyping with intracellular cytokine detection, multicolor immune-fluorescence microscopy and hybridisation were performed to characterise lesional and circulating Tfh and Tph-cells. SG-organ cultures were used to investigate functionally the blockade of T-cell costimulatory pathways on key proinflammatory cytokine production. RESULTS Transcriptomic analysis in SG identified Tfh-signature, interleukin-21 (IL-21) and the inducible T-cell co-stimulator (ICOS) costimulatory pathway as the most upregulated genes in ELS+SS patients, with parotid MALT-L displaying a 400-folds increase in IL-21 mRNA. Peripheral CD4CXC-motif chemokine receptor 5 (CXCR5)programmed cell death protein 1 (PD1)ICOS Tfh-like cells were significantly expanded in ELS+SS patients, were the main producers of IL-21, and closely correlated with circulating IgG and reduced complement C4. In the SG, lesional CD4CD45ROICOSPD1 cells selectively infiltrated ELS+ tissues and were aberrantly expanded in parotid MALT-L. In ELS+SG and MALT-L parotids, conventional CXCR5CD4PD1ICOSFoxp3 Tfh-cells and a uniquely expanded population of CXCR5CD4PD1ICOSFoxp3 Tph-cells displayed frequent IL-21/interferon-γ double-production but poor IL-17 expression. Finally, ICOS blockade in SG-organ cultures significantly reduced the production of IL-21 and inflammatory cytokines IL-6, IL-8 and tumour necrosis factor-α (TNF-α). CONCLUSIONS Overall, these findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS