Celiac Disease Prevalence is Increased in Primary Sjögren's Syndrome and Diffuse Systemic Sclerosis: Lessons from a Large Multi-Center Study.

Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p < 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p ≤ 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc-CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.

Platelets Contribute to the Accumulation of Matrix Metalloproteinase Type 2 in Synovial Fluid in Osteoarthritis.

Inflammation plays a role in the initiation and progression of osteoarthritis (OA), a chronic degenerative joint disorder. Platelets are inflammatory cells, contain and release matrix metalloproteinases (MMPs) and favour the release of these enzymes, key effectors of cartilage and subchondral bone degradation, by other cells; however, their role in OA has not been investigated yet. Our aims were (1) to assess the presence of platelets and of MMP-2 in synovial fluid (SF) of OA patients; (2) to evaluate the contribution of platelets to MMP-2 release by fibroblast-like synoviocytes (FLS); and (3) to investigate if hyaluronic acid (HA) interferes with these processes. SF was collected from 27 OA patients before and after treatment with intra-articular HA (20 mg/2 mL). Moreover, FLS were co-cultured with platelets, and the release of MMP-2 in supernatants was measured. Our results show that platelets are present in OA SF and show markers of activation. OA SF also contains relevant amounts of MMP-2. Co-incubation of platelets with FLS favours the release of MMP-2 by the interaction of platelet surface P-selectin with FLS CD44 by a mechanism involving the activation of pAkt and pSrc in FLS. Administration of HA to OA patients decreased the infiltration of platelets in SF and reduced the levels of MMP-2. The addition of HA in vitro inhibited the release of MMP-2 by FLS triggered by the interaction with platelets. In conclusion, our data show that platelets may contribute to joint degeneration in OA by favouring the accumulation of MMP-2 in SF.

One year in review 2015: systemic lupus erythematosus.

Systemic lupus erythematosus is a multiorgan autoimmune disease with a highly variable clinical course, typically involving women in childbearing age. At present, many aspects of its pathogenesis still remain unclear. Moreover, although a significant increase of patient survival has been observed in the last decades, morbidity and mortality remain high. Finally, SLE impacts negatively on the health-related quality-of-life of patients. Therefore, multiple aspects of SLE still remain challenging and it continues to be the object of both clinical and translational clinical research. Herewith, we provide a critical digest of the recent literature on this topic.

T Regulatory and T Helper 17 Cells in Primary Sjögren's Syndrome: Facts and Perspectives.

Historically, primary Sjögren's syndrome (pSS) was thought to be a T helper (h) 1 driven disease due to the predominance of CD4(+)T lymphocytes and their products in target organs and peripheral blood of patients. In the last decades, the identification of a number of T cell subsets, including Th17, T regulatory (Treg), and follicular helper T cells, challenged this long-standing paradigm and prompted to identify their role in pSS pathogenesis. In addition the impact of abnormal proinflammatory cytokine production, such as IL-6, IL-17, IL-22, and IL-23, has also attracted considerable attention. However, although several studies have been carried out in experimental models and patients with pSS, many aspects concerning the role of Treg cells and IL-17/Th17 cell system in pSS pathogenesis are not fully elucidated. In particular, the role played by different IL-17-producing T cell subsets as well as the effects of pharmacological therapies on Treg/Th17 cell balance represents an intriguing issue. The aim of this review article is to provide an overview of current knowledge on Treg cells and IL-17-producing T cells in pSS pathogenesis. We believe that these insights into pSS pathogenesis may provide the basis for successful therapeutic intervention in this disease.

Cardiovascular disease in systemic sclerosis.

Cardiovascular (CV) system involvement is a frequent complication of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). It still remains unclear if a premature atherosclerosis (ATS) occurs even in systemic sclerosis (SSc). Although microvascular disease is a hallmark of SSc, in the last few years a number of studies highlighted a higher prevalence of macrovascular disease in SSc patients in comparison to healthy individuals and these data have been correlated with a poorer prognosis. The mechanisms promoting ATS in SSc are not fully understood, but it is believed to be secondary to multi-system organ inflammation, endothelial wall damage and vasculopathy. Both traditional risk factors and endothelial dysfunction have been proposed to participate to the onset and progression of ATS in such patients. In particular, endothelial cell injury induced by anti-endothelial antibodies, ischemia/reperfusion damage, immune-mediated cytotoxicity represent the main causes of vascular injury together with an impaired vascular repair mechanism that determine a defective vasculogenesis. Aim of this review is to analyse both causes and clinical manifestations of macrovascular involvement and ATS in SSc.

Characterization of circulating endothelial microparticles and endothelial progenitor cells in primary Sjögren's syndrome: new markers of chronic endothelial damage?

OBJECTIVE: Chronic autoimmune diseases are associated with increased risk of cardiovascular death. Endothelial dysfunction represents the first stage of subclinical atherosclerosis and multiple factors contribute to endothelial injury. Among these, an altered balance between endothelial microparticle (EMP) release and endothelial progenitor cell (EPC) generation promotes endothelial dysfunction. The role of EMPs and EPCs in promoting endothelial damage in primary SS (pSS) has never been investigated. Our aim was to evaluate the role of EMPs and EPCs as markers of endothelial damage in pSS and their correlation with disease clinical and immunological features. METHODS: Circulating EMPs (CD31(+)/CD42(-)), true EPCs (CD34(+)/KDR(+)/CD133(+)) and mature EPCs (CD34(+)/KDR(+)/CD133(-)) were quantified by FACS analysis in 34 pSS patients and 18 age- and sex-matched controls. Correlation between EMP and EPC levels and parameters of disease activity and damage, clinical features and markers of immunological dysfunction was performed. RESULTS: Patients displayed higher EMP numbers with respect to healthy controls [HCs; mean 450 n/µl (S.D. 155) vs 231 (110), P < 0.0001]. EPC and mature EPC levels were higher in patients compared with HCs [mean 226 n/ml (S.D. 181) vs 69 (53), P < 0.001 and 166 (161) vs 36 (32), P < 0.0001, respectively). EMP levels directly correlated with disease duration from symptoms and diagnosis (ρ = 0.5, P < 0.01). Early EPCs inversely correlated with disease duration from symptoms (ρ = -0.5, P < 0.01) and diagnosis (ρ = -0.4, P < 0.05). CONCLUSION: This is the first demonstration of chronic endothelial fragmentation characterizing pSS. The reparative potentiality of the endothelial layer appears to be preserved in the earliest stages of disease. During the course of the disease, progressive exhaustion of the precursor endothelial pool may be hypothesized, leading to defective vascular layer restoration and endothelial dysfunction.

Images in clinical medicine: Unusual bursal fluid.

A 73-year-old man with seropositive rheumatoid arthritis and extraarticular involvement (rheumatoid nodules on the right elbow) presented with persistent, painless swelling of the left elbow. His medical history was unremarkable except for hypertension.