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Objectives: Autoimmune rheumatic diseases (ARDs) affect women of childbearing age and have been associated with adverse birth outcomes. The impact of diseases like ankylosing spondylitis and psoriatic arthritis (PsA) on birth outcomes remains less studied to date. Our objective was to evaluate the impact of ARDs on preterm birth (PTB), congenital anomalies, low birth weight (LBW) and small for gestational age (SGA), in a large cohort of women., Methods: We conducted a propensity score-matched analysis to predict ARD from a retrospective birth cohort of all live, singleton births in California occurring between 2007 and 2012. Data were derived from birth certificate records linked to hospital discharge International Classification of Diseases, ninth revision codes., Results: We matched 10 244 women with a recorded ARD diagnosis (rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), antiphospholipid syndrome, PsA); ankylosing spondylitis and juvenile idiopathic arthritis (JIA) to those without an ARD diagnosis. The adjusted OR (aOR) of PTB was increased for women with any ARD (aOR 1.93, 95% CI 1.78 to 2.10) and remained significant for those with RA, SLE, PsA and JIA. The odds of LBW and SGA were also significantly increased among women with an ARD diagnosis. ARDs were not associated with increased odds of congenital anomalies., Conclusion: Consistent with prior literature, we found that women with ARDs are more likely to have PTB or deliver an SGA infant. Some reassurance is provided that an increase in congenital anomalies was not found even in this large cohort., Competing Interests: Competing interests: None declared.

Epitope mapping of anti-Ro52 antibodies (Abs) has been extensively studied in patients with Sjögren's syndrome (SjS) and systemic lupus erythematosus (SLE). Comprehensive epitope mapping in systemic sclerosis (SSc), where anti-Ro52 antibodies are also frequently detected, has not been performed. The aim of the present study was to fully characterize Ro52 epitopes in anti-Ro52-positive SSc using Ro52 fragments spanning the full antigen. Further analysis was made according to anti-Ro60 status. Epitope mapping was performed in 43 anti-Ro52-positive SSc patients. Seventy eight anti-Ro52-positive pathological controls, including 20 patients with SjS, 28 patients with SLE, 15 patients with dermatomyositis (DM), and 15 patients with primary biliary cholangitis (PBC), and 20 anti-Ro52-negative healthy individuals as normal controls were also tested. Five recombinant Ro52 fragments [Ro52-1 (aa 1-127), Ro52-2 (aa 125-268), Ro52-3 (aa 268-475), Ro52-4 (aa 57-180), and Ro52-5 (aa 181-320) were used to test reactivity by line-immunoassay and in house ELISA. Anti-Ro60 reactivity was tested by ELISA. All anti-Ro52 positive sera reacted with Ro52-2; none recognized Ro52-3. Antibodies against Ro52-1 were less frequently found in SSc than in SjS/SLE (11.6 vs. 41.7%, p = 0.001); and antibodies against Ro52-4 were less frequently found in SSc than in SjS/SLE (27.9 vs. 50%, p = 0.03). In SSc patients, reactivity against Ro52-1 was more frequent in anti-Ro52+/anti-Ro60+ than in anti-Ro52+/anti-Ro60-patients (33.3 vs. 0%, p = 0.003). In this comprehensive analysis of Ro52 epitope mapping in SSc, the coiled coil domain remains the predominant epitope on Ro52. Contrary to SjS and SLE, patients with SSc fail to identify epitopic regions within the N-terminus of the protein, especially if they lack con-current anti-Ro60 reactivity.

ABSTRACT Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases.

Background: Women with autoimmune rheumatic diseases (ARDs) find it difficult to get information and support with family planning, pregnancy, and early parenting. A systematic approach to prioritising research is required to accelerate development and evaluation of interventions to meet the complex needs of this population.  Methods: A Nominal Group Technique (NGT) exercise was carried out with lay and professional stakeholders (n=29). Stakeholders were prepared for debate through presentation of available evidence. Stakeholders completed three tasks to develop, individually rank, and reach consensus on research priorities: Task 1 - mapping challenges and services using visual timelines; Task 2 - identifying research topics; Task 3 - individually ranking research topics in priority order. Results of the ranking exercise were fed back to the group for comment.   Results: The main themes emerging from Task 1 were the need for provision of information, multi-disciplinary care, and social and peer support. In Task 2, 15 research topics and 58 sub-topics were identified around addressing the challenges and gaps in care identified during Task 1.  In Task 3, a consensus was reached on the ten research topics that should be given the highest priority. These were individually ranked, resulting in the following order of priorities (from 1 - highest to 10 - lowest): 1. Shared decision-making early in the care pathway; 2. Pre-conception counseling; 3. Information about medication use during pregnancy/breastfeeding; 4. Personalised care planning; 5. Support for partners/family members; 6. Information about local support/disease specific issues; 7. Shared decision-making across the care pathway; 8. Peer-support; 9. Social inequalities in care, and; 10. Guidance on holistic/alternative therapies.    Conclusions: This systematic approach to identification of research priorities from a multi-disciplinary and lay perspective indicated that activities should focus on development and evaluation of interventions that increase patient involvement in clinical decision-making, multi-disciplinary models of care, and timely provision of information., Competing Interests: No competing interests were disclosed.

Indirect immunofluorescence (IIF) is considered by the American College of Rheumatology (ACR) and the international consensus on ANA patterns (ICAP) the gold standard for the screening of anti-nuclear antibodies (ANA). As conventional IIF is labor intensive, time-consuming, subjective, and poorly standardized, there have been ongoing efforts to improve the standardization of reagents and to develop automated platforms for assay incubation, microscopy, and evaluation. In this study, the workflow and performance characteristics of a fully automated ANA IIF system (Sprinter XL, EUROPattern Suite, IFA 40: HEp-20-10 cells) were compared to a manual approach using visual microscopy with a filter device for single-well titration and to technologist reading. The Sprinter/EUROPattern system enabled the processing of large daily workload cohorts in less than 8 h and the reduction of labor hands-on time by more than 4 h. Regarding the discrimination of positive from negative samples, the overall agreement of the EUROPattern software with technologist reading was higher (95.6%) than when compared to the current method (89.4%). Moreover, the software was consistent with technologist reading in 80.6-97.5% of patterns and 71.0-93.8% of titers. In conclusion, the Sprinter/EUROPattern system provides substantial labor savings and good concordance with technologist ANA IIF microscopy, thus increasing standardization, laboratory efficiency, and removing subjectivity.

Background: Autoimmune rheumatic diseases (ARDs), involving immune disturbances resulting from auto-inflammatory mechanisms, are a group of diseases characterized by autoimmunity and autoimmunemediated organ damage. Thymoma, whose mechanism is also associated with immune abnormalities, is the most common neoplasm of the anterior mediastinum. But thymoma with ARDs is relatively less frequent. The clinical characteristics of the coexistence of ARDs and thymomas are still not very clear. And the therapeutic strategy for ARDs combined with thymomas varies, with an uncertain outcome., Objectives: The aim of this study was to investigate the clinical characteristics of the coexistence of ARDs and thymomas in order to speculate whether a thymectomy is effective for ARDs combined with thymomas, and to seek the proper therapeutic strategy for treating ARDs combined with thymomas., Material and Methods: We presented 2 cases of the coexistence of ARDs and thymomas. Then, we summarized 20 cases (including our 2 cases) in which the ARD was diagnosed concurrently with, or prior to, the thymoma., Results: Pure red cell aplastic anemia (PRCA) might be associated with an ARD and a thymoma, and a thymectomy may lead to the appearance, exacerbation, or remission of ARDs., Conclusions: Searching for a thymoma is necessitated if a patient with ARDs experiences PRCA and the effects of thymectomy in ARDs combined with thymomas may be associated with the onset sequence of ARDs and thymomas.

Progressive multifocal leukoencephalopathy (PML) is a rare, typically fatal, demyelinating central nervous system infection caused by reactivation of the John Cunningham virus that generally occurs in immunosuppressed patients. With an evolving understanding of a greater clinical heterogeneity of PML and significant implications for therapy, PML should be considered in the differential diagnosis of neurologic presentations of rheumatic diseases. Increased awareness of PML among rheumatologists is required, as earlier diagnosis and restoration of immune function may improve the otherwise grim prognosis associated with PML., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Antibodies against carbamylated proteins (anti-CarP) have been recently identified in the sera of patients with rheumatoid arthritis (RA). The objective of the study was to evaluate the prevalence, sensitivity and specificity of anti-CarP compared to anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF), replicating the existing data in a large cohort of Italian patients with RA and extending the evaluation to other autoimmune rheumatic diseases (AIRDs)., Methods: Serum samples (n = 607) from 309 patients with RA, 200 disease controls and 98 normal healthy subjects (NHS) were evaluated. Anti-CarP were detected using carbamylated fetal calf serum as the antigen. ACPAs were detected using second-generation ELISA and IgM RF was assessed as part of routine analysis., Results: Anti-CarP antibodies were detected in 117 patients with RA (34.4%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were detected in 33 patients (16.5%), ACPA in 29 patients (14.5%) and RF in 64 patients (32%). In particular, 16.8% of patients with systemic lupus erythematosus and 31.1% of patients with Sjögren syndrome were positive for anti-CarP. The sensitivity of anti-CarP, ACPA and RF was 46.8%, 61.8% and 64.4%, respectively and specificity was 91.95%, 89.93% and 76.51%, respectively., Conclusions: The present study extends the knowledge of anti-CarP antibodies, confirming previous data on the diagnostic accuracy of anti-CarP in RA in a large cohort of Italian patients. Anti-CarP antibodies demonstrated relatively low sensitivity and slightly higher specificity compared to ACPA and RF. Even if predominantly present in RA, anti-CarP was detected in a variable percentage of patients with other autoimmune rheumatic diseases and their generation could be attributed to the inflammatory status; the clinical relevance of anti-CarP antibodies in these latter patients should be further determined.

Orofacial manifestations occur frequently in rheumatic diseases and usually represent early signs of disease or of its activity that are still neglected in clinical practice. Among the autoimmune rheumatic diseases with potential for oral manifestations, rheumatoid arthritis (RA), inflammatory myopathies (IM), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), relapsing polychondritis (RP) and Sjögren's syndrome (SS) can be cited. Signs and symptoms such as oral hyposalivation, xerostomia, temporomandibular joint disorders, lesions of the oral mucosa, periodontal disease, dysphagia, and dysphonia may be the first expression of these rheumatic diseases. This article reviews the main orofacial manifestations of rheumatic diseases that may be of interest to the rheumatologist for diagnosis and monitoring of autoimmune rheumatic diseases., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

We aimed to determine the prevalence of hypovitaminosis D in patients with autoimmune rheumatic diseases (ARDs) in China and its association with demographic characteristics of the patients. We recruited 384 patients in this cross-sectional study including 121 cases of systemic lupus erythematosus (SLE), 131 rheumatoid arthritis (RA), 102 spondyloarthritis (SpA) and 30 other ARDs. For each patient, demographic information was collected and serum concentration of 25OHD3 was measured by electrochemiluminescence immunoassay (ECLIA). The multivariate logistic regression model was used to investigate the association between vitamin D deficiency and patient characteristics. The mean serum vitamin D level of the 384 patients was 18.91 (8.12) ng/mL, and the median age was 37.33 (12.01) yrs. Among these patients, 222 (57.81%) and 127 (33.07%) were found to be vitamin D deficiency and insufficiency, respectively. From the disease perspective, the percentages of insufficiency and deficiency were as follow: 97.52% and 84.30% in SLE, 87.02% and 48.85% in RA, 88.24% and 40.20% in SpA, 90.89% and 57.81% in other ARDs patients. The causative factors for vitamin D deficiency included SLE per se (OR 12.54, P < 0.001) and high body mass index (BMI) (OR 1.88, P < 0.001). However, the seniors were less likely to have vitamin D deficiency (OR 0.95, P = 0.005). No correlation was disclosed between vitamin D deficiency and gender or disease duration. Hypovitaminosis D is highly prevalent among autoimmune rheumatic diseases population in China. The SLE per se and the obesity are the risk factors for vitamin D deficiency. Clinicians are advised to supplement vitamin D in these patients.

Targeted strategies for reducing the increased risk of infection in patients with autoimmune rheumatic diseases include vaccinations as well as antibiotic prophylaxis in selected patients. However, there are still issues under debate: Is vaccination in patients with rheumatic diseases immunogenic? Is it safe? What is the impact of immunosuppressive drugs on vaccine immunogenicity and safety? Does vaccination cause disease flares? In which cases is prophylaxis against Pneumocystis jirovecii required? This review addresses these important questions to which clinicians and researchers still do not have definite answers. The first part includes immunization recommendations and reviews current data on vaccine efficacy and safety in patients with rheumatic diseases. The second part discusses prophylaxis for Pneumocystis pneumonia., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Widespread use of immunosuppressive drugs, both conventional disease-modifying antirheumatic drugs (cDMARDs) and biologic disease-modifying antirheumatic drugs (bDMARDs), in autoimmune rheumatic diseases (ARDs) has been found to be associated with the reactivation of underlying latent viruses. The clinical features of virus reactivation can sometimes mimic flare of the underlying ARDs. The correct diagnosis and management of such reactivation is crucial, as increasing the dose of immunosuppressive drugs to treat a presumed flare of underlying ARDs would probably be of no benefit, and it could exert a detrimental effect on the host. This review focused on the effects of immunosuppressive drugs on underlying chronic viral infections, particularly hepatitis B virus, hepatitis C virus, human immunodeficiency virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, John Cunningham (JC) virus, Kaposi sarcoma-associated herpesvirus, and human papillomavirus in patients with ARDs. It also covered the effect of interferon-α, which is used to treat chronic hepatitis infection, and the induction of autoimmunity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Abstract: Epidemiological and experimental immunological evidence suggest that estrogens enhance the humoral immune response, and at the same time, seem to play important roles in pathophysiology of autoimmune rheumatic diseases. Estrogens in human subjects are generally considered as enhancers of cell proliferation (anti-apoptotic), however, rather than through their serum levels (that may exert opposite dose-related effects), they play important roles through their peripheral metabolites especially in autoimmune rheumatic diseases. Several investigations strongly support an accelerated aromatase-mediated peripheral metabolic conversion of upstream androgen precursors to estrogen metabolites in peripheral tissues affected by immune/inflammatory reactions, both, in male and female patients. In RA synovial tissue, biological effects of these metabolites as a consequence of altered peripheral sex hormone synthesis (intracrine, e.g., at the level of macrophages and fibroblasts) mainly results in stimulation of cell proliferation and cytokine production (i.e. TNF). It was shown that RA synovial cells mainly produce the cell proproliferative 16alpha-hydroxyestrone which, in addition to 16alpha-hydroxy-17beta-estradiol, is the downstream estrogen metabolite that interferes with monocyte proliferation. Therefore, a preponderance of 16alpha-hydroxylated estrogens is an unfavorable sign, at least, in synovial inflammation and possibly related synovial tissue hyperplasia. Interestingly, urinary concentration and total urinary loss of 2-hydroxyestrogens was found 10 times higher in healthy subjects compared to RA or SLE patients irrespective of prior prednisolone treatment or sex. The intracrine synthesis of active estrogen metabolites at the level of cells involved in the immune response (e.g. macrophages and fibroblasts) represents a common pathway that characterizes a similar final immune reactivity in both male and female patients. [Copyright &y& Elsevier]