Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30118900 The role of stress in the mosaic of autoimmunity: An overlooked association. 2018 Oct Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (T(h)2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (T(h)1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.
30149308 Proposing novel TNFα direct inhibitor Scaffolds using fragment-docking based e-pharmacoph 2018 Oct Tumor necrosis factor alpha (TNFα) is a homotrimer protein that plays a pivotal role for critical immune functions, including infection, inflammation and antitumor responses. It also plays a primary role in autoimmune diseases like rheumatoid arthritis (RA). So far, only biological therapeutics like infliximab, etanercept, and adalimumab are available as treatment of inflammatory diseases. They directly bind to TNFα and interrupt its binding to its receptor protein tumor necrosis factor receptor (TNFR). However, they may also cause serious side effects such as activating an autoimmune anti-antibody response or the weakening of the body's immune defenses. Thus, small molecule-based therapies can be considered as alternative methods. In this study, a novel method is applied to develop energetically optimized, structure-based pharmacophore models for rapid in silico drug screening. Fragment-based docking results were used in the construction of an universal e-pharmacophore model development. The developed model is then used for screening of small-molecule library Specs-screening compounds (Specs-SC) which includes more than 200.000 drug-like molecules. In another approach, binary QSAR-based models were used to screen Specs-SC, as well as Specs-natural products (NP) which has around 750 compounds, and a library of drugs registered or approved for use in humans NIH's NCGC pharmaceutical collection (NPC) which has around 7500 molecules. The MetaCore/MetaDrug platform was used for binary QSAR models for therapeutic activity prediction as well as pharmacokinetic and toxicity profile predictions of screening molecules. This platform is constructed based on a manually curated database of molecular interactions, molecular pathways, gene-disease associations, chemical metabolism, and toxicity information. Molecular docking and molecular dynamics (MD) simulations were performed for the selected hit molecules. As target protein, both homodimer and homotrimer forms of TNFα were considered. The screening results showed that indinavir and medroxalol from NPC chemical library and a set of compounds (AT-057/43115940, AP-970/42897107, AK-968/41925665, AI-204/31679053, AN-648/41666950, AN-698/42006940) from Specs-SC database were identified as safe and active direct inhibitors of TNFα.
29671827 Molecular Modeling Studies on Carbazole Carboxamide Based BTK Inhibitors Using Docking and 2018 Apr 19 Rheumatoid arthritis (RA) is the second common rheumatic immune disease with chronic, invasive inflammatory characteristics. Non-steroidal anti-inflammatory drugs (NSAIDs), slow-acting anti-rheumatic drugs (SAARDs), or glucocorticoid drugs can improve RA patients’ symptoms, but fail to cure. Broton’s tyrosine kinase (BTK) inhibitors have been proven to be an efficacious target against autoimmune indications and B-cell malignancies. Among the current 11 clinical drugs, only BMS-986142, classified as a carbazole derivative, is used for treating RA. To design novel and highly potent carbazole inhibitors, molecular docking and three dimensional quantitative structure⁻activity relationship (3D-QSAR) were applied to explore a dataset of 132 new carbazole carboxamide derivatives. The established comparative molecular field analysis (CoMFA) (q² = 0.761, r² = 0.933) and comparative molecular similarity indices analysis (CoMSIA) (q² = 0.891, r² = 0.988) models obtained high predictive and satisfactory values. CoMFA/CoMSIA contour maps demonstrated that bulky substitutions and hydrogen-bond donors were preferred at R₁ and 1-position, respectively, and introducing hydrophilic substitutions at R₁ and Râ‚„ was important for improving BTK inhibitory activities. These results will contribute to the design of novel and highly potent BTK inhibitors.
29922101 Metabolic syndrome in adults with a history of juvenile arthritis. 2018 OBJECTIVE: The objective of this study was to determine the risk of obesity and metabolic syndrome in adults with a history of juvenile arthritis (JA). METHODS: Using the National Health and Nutrition Examination Survey (NHANES), we compared the characteristics of respondents with arthritis (JA vs rheumatoid arthritis [RA]) to those of the control group without arthritis. We used logistic regression analyses, controlling for age, race, and gender, to determine the ORs for metabolic syndrome. RESULTS: Obesity was increased in the JA group with 67% respondents having body mass index ≥30 kg/m(2) vs 55% respondents in the no arthritis cohort (p=0.004). In unadjusted analyses, there was increased odds of metabolic syndrome in JA (OR 6.2, p=0.001) and RA groups compared to those without arthritis (OR 7.7, p=0.001). After adjusting for age, gender, and race, the odds of metabolic syndrome remained increased in JA (OR 5.2, p=0.001) and RA (OR 3.2, p=0.001) groups. CONCLUSION: Adults with a history of JA have a significantly increased risk of metabolic syndrome compared to those without arthritis. These findings are important because metabolic syndrome has been associated with an increased risk of cardiovascular disease and death in other populations.
29786572 Dysadipokinemia in patients with gout and its association with the disease activity. 2018 OBJECTIVE: Introduction: In recent years, the role of adipokines in the development of rheumatic diseases has been a pressing issue. The available data suggest the dysadipokinemia in patients with rheumatoid arthritis, osteoarthritis and psoriatic arthritis. However, there is no data on changes in the levels of adipokines in patients with gout and their association with the activity of inflammatory process. The aim was to study the levels of adipokines in gout patients and evaluate their association with the disease activity. PATIENTS AND METHODS: Materials and methods: We examined 151 male patients with gout. The control group consisted of 31 practically healthy men, represented by age. We used the Gout Activity Score (GAS) to assess gout severity. The levels of leptin and adiponectin were determined using the ELISA kit. For comprehensive evaluation of dysadipokinemia, we used a logarithmic ratio of leptin to adiponectin (lg A/L). Primary processing of results was carried out using MS Excel and Statistica SPSS22 statistical software packages. RESULTS: Results: The patients with gout demonstrated higher leptin levels, lower levels of adiponectin, and lower lg A/L compared to practically healthy individuals. Among patients with gout, the disturbance of adipokin status was most pronounced in patients with tophi. Patients with high GAS activity had maximum disturbance of adipokin profile by lg A/L, while the manifestations of dysadipokinemia were minimal in the group with low activity of the disease. It was established that GAS disease activity, BMI, and the number of joints under attack may be considered the most significant independent predictors of dysadipokinemia. CONCLUSION: Conclusions: The patients with gout presented an increase in leptin level, a decrease in adiponectin level, and a decrease in the ratio lg A/L. Dysadipokinemia was associated with high disease activity and could serve as a prognostic factor for assessing the severity of the disease.
30405736 Pharmacologic Effect of Miao Medicine Illicium simonsii Maxim. on Collagen-Induced Arthrit 2018 OBJECTIVES: To study the pharmacologic effect and mechanism of action of Miao medicine Illicium simonsii Maxim. (ISM) in treating rheumatoid arthritis. METHODS: Sixty rats were randomly divided to six groups: normal control (normal), collagen-induced arthritis (CIA) model (model), CIA + tripterygium glycosides (TG), CIA + ISM high dose oral (ISM-H), CIA + ISM low-dose oral (ISM-L), and CIA + ISM topical application (ISM-T). The treatment doses were selected based on published reports and folk medicine practice. The outcome measurements included paw swelling, joint pathology, organ index, blood count, T helper 17 (Th17) cell count, and interleukin-6 (IL-6) level. RESULTS: Compared to the CIA model group, all treatment groups showed a significant reduction in paw swelling, blood vessel pathology, Th17 cell count, and IL-6 levels (p < 0.05 or p < 0.01). All treatment groups showed alleviated foot swelling and lower total number of white blood cells, and these effects were observed earlier with oral ISM than topical ISM. The effect of ISM was weaker than that of TG. In addition, less organ damage was observed with topical ISM than oral ISM but better than TG. CONCLUSIONS: These results suggest that, by downregulating Th17 cells, ISM inhibits the production of Il-6, thereby alleviating the proliferation of endothelial and rheumatoid-like cells and leukocytosis in CIA rats, ultimately eliminating foot swelling.
30348449 Therapeutic tolerance in autoimmune disease. 2018 Dec Experimental immune tolerance induction, enabling tissues to be transplanted across animal strains, was first demonstrated in the 1950s. Therapeutic tolerance induction, whereby immune tolerance is used to treat or prevent transplant rejection, and as a treatment for autoimmunity, followed in the 1980s. Clinical translation has been slow but the pace of change is accelerating. Numerous strategies are now being tested clinically, ranging from monoclonal antibodies against T-cells, to peptide therapies, cellular therapies and microbiome manipulation. Furthermore, technology has advanced to the stage where we can start to monitor serological and cellular autoreactivity as biomarkers of response. In terms of autoimmunity, recognition of the prolonged phase of preclinical autoimmunity in several conditions, is leading to debate around treatment of at risk individuals, and trials in patients with prodromal clinical symptoms, such as seropositive arthralgia. Additionally, potent immunomodulatory drugs are achieving a substantial track record of safety. Putting these various factors together suggests that we can soon expect to see more trials of tolerogenic strategies in pre-clinical disease, with intensive immune monitoring to guide therapy.
30295434 Long-Term Safety of Rituximab in Rheumatoid Arthritis: Analysis From the SUNSTONE Registry 2018 Oct 8 OBJECTIVE: To evaluate the long-term safety of rituximab in an observational cohort of patients with rheumatoid arthritis (RA) who had an inadequate response to ≥ 1 antitumor necrosis factor therapies in the United States (SUNSTONE Registry). METHODS: In this prospective, observational cohort study, patients received rituximab according to their physician's standard practice and were evaluated at standard-of-care follow-up visits at least every 6 months. The primary outcome was the incidence of protocol-defined significant infections. Secondary outcomes included serious adverse events potentially associated with rituximab, cardiovascular or thrombotic (CVT) events, seizures, deaths and pregnancies. Posthoc analyses assessed outcomes by concomitant medication use. RESULTS: Overall, 989 patients (safety-evaluable population) received ≥ 1 dose of rituximab, with a total follow-up of 3844 patient-years (PYs; mean duration, 3.9 years). In total, 341 significant infections occurred in 197 patients (19.9%). The incidence rates (95% CI) for significant infections, CVT events, and seizures were 8.87 (7.98, 9.86), 1.95 (1.56, 2.45), and 0.18 (0.09, 0.38) per 100 PYs, respectively. The incidence of significant infections did not increase with time or with cumulative rituximab exposure. During the study, 64 patients died (crude mortality [95% CI]: 1.66 per 100 PYs [1.30, 2.13]). The most common causes of death were infections (19 patients), malignancy (14), and cardiovascular events (13). Eight pregnancies were reported in 7 patients. CONCLUSION: In patients with RA treated with rituximab for up to 5 years, the rates of significant infections were stable over time and higher in patients who received long-term systemic steroid treatment. This article is protected by copyright. All rights reserved.
29610698 Three Case Reports of Rhupus Syndrome: An Overlap Syndrome of Rheumatoid Arthritis and Sys 2018 We present the clinical and serological characteristics of three patients with rhupus. The 3 patients with rhupus presented ACR criteria for SLE as well as for RA, ANA positive with a titer of 1/100 in all patients, and positive anti-DNA in 2 of the 3 patients, with the predominance of symmetrical polyarthritis. We found anti-CCP positivity and rheumatoid factor positivity and high titers in all patients, positive anti- anti-SSA in one patient, and positive anti- anti-Sm in one patient. Renal and liver function tests were normal in all patients. The 3 patients achieved clinical remission with DMARD treatment.
25294686 Amelioration of oxidative stress in the joint tissue may be the basis for the antiarthriti 2018 Dec AIM: In this study we have evaluated the antioxidant and antiarthritic activity of Terminalia arjuna bark extract (TABE) in collagen-induced arthritis (CIA) in rats. METHODS: Arthritis was induced in rats by intradermal injection of the collagen-complete Freund's adjuvant emulsion. Right hind paw thickness was measured as a primary marker for severity of arthritis. Biochemical parameters such as tissue levels of superoxide dismutase (SOD), catalase, reduced glutathione (GSH), nitrites and thiobarbituric acid reactive substances (TBARS) were measured to determine the effect of treatment on antioxidant defenses. Articular elastase (ELA) level in the arthritic tissue was measured as a marker for neutrophil infiltration. RESULT: Terminalia arjuna bark extract administration significantly inhibited the increase in paw thickness induced by immunization with collagen as compared to CIA-control animals. Further, it attenuated the fall in tissue SOD and GSH levels and mitigated the increase in tissue nitrites and TBARS levels as compared to CIA-control animals. Tissue ELA levels, which were significantly increased in the CIA-control animals as compared to normal animals were also significantly reduced by TABE administration. CONCLUSION: Results of our study demonstrate the antioxidant and antiarthritic activity of TABE in CIA in rats. We believe that TABE could find clinical application in the management of rheumatoid arthritis and associated disorders.
29845272 Therapeutic effect of the natural compounds baicalein and baicalin on autoimmune diseases. 2018 Jul A series of natural compounds have been implicated to be useful in regulating the pathogenesis of various autoimmune diseases. The present study demonstrated that the Scutellariae radix compounds baicalein and baicalin may serve as drugs for the treatment of autoimmune diseases, including rheumatoid arthritis and inflammatory bowel disease. Following the administration of baicalein and baicalin in vivo, T cell‑mediated autoimmune diseases in the mouse model were profoundly ameliorated: In the collagen‑induced arthritis model (CIA), the severity of the disease was reduced by baicalein and, consistently, baicalein was demonstrated to suppress T cell proliferation in CIA mice. In the dextran sodium sulfate (DSS)‑induced colitis model, the disease was attenuated by baicalin, and baicalin promoted colon epithelial cell (CEC) proliferation in vitro. The present study further revealed that the mRNA expression of signal transducer and activator of transcription (STAT)3 and STAT4 in the tyrosine‑protein kinase JAK‑STAT signaling pathway in T cells was downregulated by baicalein, contributing to its regulation of T cell proliferation. However, in the DSS model, the STAT4 transcription in CECs, which are the target cells of activated T cells in the gut, was downregulated by baicalin, suggesting that baicalein and baicalin mediated similar STAT expression in different cell types in autoimmune diseases. In conclusion, the similarly structured compounds baicalein and baicalin selectively exhibited therapeutic effects on autoimmune diseases by regulating cell proliferation and STAT gene expression, albeit in different cell types.
29998578 Salivary S100A8/A9 in Sjögren's syndrome accompanied by lymphoma. 2018 Oct BACKGROUND: Sjögren's syndrome (SS) is an autoimmune inflammatory disease that affects the exocrine glands. The absence of early diagnostic markers contributes to delays in its diagnosis. Identification of changes in the protein profile of saliva is considered one of the promising strategies for the discovery of new biomarkers for SS. OBJECTIVE: To identify salivary protein biomarkers with potential for use in discriminating between different lymphoma risk subgroups of SS. METHOD: Parotid and whole mouth saliva samples were collected from patients with SS, including those in subgroups at higher risk of developing or with confirmed lymphoma, non-SS sicca disease controls and healthy subjects. An initial proteomics analysis by mass spectrometry (LCMSMS) identified S100A8/A9 as a biomarker and was followed by validation with an enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant differences were found in levels of S100A8/A9 in parotid saliva but not whole mouth saliva between patients with SS compared with healthy and disease control subjects (P = 0.001 and 0.031, respectively). Subgroups of patients with SS based on lymphoma risk showed significant differences in salivary levels of S100A8/A9. CONCLUSION: The results suggest that salivary levels of S100A8/A9 can aid in differentiating between SS, disease control and healthy control subjects, especially the subgroups of SS with lymphoma or at higher risk of lymphoma.
29901591 Prevalence, risk factors, and prognosis of interstitial lung disease in a large cohort of 2018 Jun To determine the prevalence of pulmonary complications in primary Sjögren syndrome (pSS), and to identify the risk factors and the prognosis associated with pulmonary involvement in pSS patients.A total of 1341 hospitalized patients (853 with pSS and 488 with secondary Sjögren syndrome [sSS]) were retrospectively reviewed. Of these, 165 hospitalized patients with pSS-associated interstitial lung disease (ILD) were analyzed and recruited as a study group. Eighty-four pSS patients without organ damage were included as a control group.One hundred and sixty-five patients (19.34%) from the pSS group and 126 patients (25.82%) from the sSS group presented with lung involvement. Of the 165 pSS patients with lung complications, 151 (91.5%) were women. The mean age was 61.25 ± 9.79 years, and the median disease duration was 84 (24-156) months. Non-specific interstitial pneumonia (NSIP; 39.1%) was the predominant pattern on high-resolution computed tomography (HRCT). The total HRCT score was 9.71 ± 4.77. Impairment in diffusion capacity was the most common (74.3%) and severe complication (predicted value of TLCO was 57.5 ± 21.2%). The 5-year survival rate for all patients with pSS-ILD was 88.5%. Age, disease duration, rheumatoid factor (RF), and C-reactive protein (CRP) were significantly higher than in controls, whereas anti-SSA was less common. Age, RF, and CRP were independent predictors of ILD after adjustment for confounders.Lung involvement is a common and severe complication of Sjögren syndrome. Age and disease activity are correlated with pulmonary involvement in pSS patients.
29708939 Outcomes of Thermal Pulsation Treatment for Dry Eye Syndrome in Patients With Sjogren Dise 2018 Sep PURPOSE: To evaluate the clinical outcomes of thermal pulsation treatment in patients with meibomian gland dysfunction (MGD) and dry eye secondary to Sjogren disease. METHODS: Twenty-four eyes from 13 patients with previously diagnosed Sjogren disease who presented to our institution with dry eye symptoms and had thermal pulsation treatment were prospectively followed up. Patients underwent comprehensive slit-lamp examination, including MGD grading, gland oil flow, corneal and conjunctival staining scores, and tear break-up time (TBUT). Tear osmolarity was tested before and after treatment. RESULTS: The average patient age was 62.4 years (range, 31-78 yrs); 12 were women and 1 a man. The average meibomian gland oil flow score showed an increase from pretreatment 0.71 to 1.75 at 1 year posttreatment (range 9-15 months) (P = 0.001). The average corneal staining score decreased from a pretreatment grade of 1.04 to a posttreatment grade of 0.36 (P < 0.001). The average conjunctival staining score decreased from a pretreatment grade of 1.5 to a posttreatment grade of 0.48 (P < 0.001). The average tear break-up time improved from 3.8 seconds before treatment to 7.5 seconds after thermal pulsation treatment (P < 0.001). There was no statistically significant change in the tear osmolarity or Ocular Surface Disease Index score. CONCLUSIONS: Our findings suggest that MGD is an important contributor to dry eye disease in patients with Sjogren disease and should not be overlooked when considering treatment options. Thermal pulsation is a therapeutic option for patients with Sjogren disease who have MGD and dry eye symptoms. After a single treatment, patients exhibited increased oil flow and tear break-up time with an associated decrease in corneal and conjunctival staining.
29275334 Effect of rituximab on a salivary gland ultrasound score in primary Sjögren's syndrome: r 2018 Mar OBJECTIVES: To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren's syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. METHODS: Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0-11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point. RESULTS: 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were -1.2 (95% CI -2.1 to -0.3; P=0.0099) and -1.2 (95% CI -2.0 to -0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48. CONCLUSIONS: We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker. TRIAL REGISTRATION NUMBER: 65360827, 2010-021430-64; Results.
29117464 Salivary scintigraphy for Sjögren's syndrome in patients with xerostomia: A retrospective 2018 May OBJECTIVES: The value of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome remains controversial. The primary aim of this study was to estimate the diagnostic accuracy of salivary gland scintigraphy in the diagnosis of Sjögren's syndrome among 237 patients with xerostomia. METHODS: We retrospectively compared eight scintigraphy parameters between 106 Sjögren patients and 131 non-Sjögren patients. RESULTS: Seven of the eight parameters were significantly decreased in patients with Sjögren; however, their diagnostic accuracy was low, with areas under the curves (AUCs) ranging from 0.58 (95% CI 0.50-0.65) to 0.63 (95% CI: 0.55-0.70). The prestimulatory oral activity index allowed discrimination between primary and secondary Sjögren's syndrome (AUC 0.73, 95% CI: 0.62-0.84), and the secretion velocity for parotid glands allowed discrimination between patients with Sjögren and burning mouth syndrome (AUC 0.71, 95% CI 0.59-0.82). CONCLUSION: The accuracy of scintigraphy parameters for the diagnosis of Sjögren's syndrome among patients with xerostomia was low; however, some functional indices appeared to assist discrimination between primary and secondary SS patients and between subgroups of patients with different causes of xerostomia.
30047438 Cutaneous vasculitis in rheumatologic disease: Current concepts of skin and systemic manif 2018 Jul Cutaneous vasculitis may be limited to the skin, a manifestation of systemic vasculitis, or a sign of an important underlying disease state. A thorough and systematic approach is required for accurate diagnosis and evaluation of such patients to enable appropriate management of the vasculitis and any associated condition. Occasionally, cutaneous vasculitis is a manifestation or presenting sign of connective tissue disease, such as systemic lupus erythematosus, Sjögren syndrome, or another condition. Such patients are at risk for poor outcomes related to systemic manifestations of vasculitis, as well as increased severity of the underlying disease. Recognition of this important subset of patients with skin vasculitis enables appropriate workup and successful management.
30282440 Histopathology of salivary glands. 2018 Oct 3 Salivary gland (SG) biopsy is a technique broadly applied for the diagnosis of primary Sjögren's syndrome (pSS), lymphoma accompanying SS, sarcoidosis, amyloidosis, and IgG4-related disease The most peculiar feature of pSS on biopsy is focal lymphocytic sialadenitis. In the past, several histological scores have been reported in the literature to describe glandular involvement during pSS. However, the variability among centres in reporting glandular scores is one of the rationales behind the development of standardised consensus guidance. SGs as well as lacrimal glands are involved in up to 50% of patients with IgG4-related disease with 3 histopathological hallmarks such as dense lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis. SGs can be also affected by amyloidosis with MSG biopsy being more sensitive than that of rectal mucosa or subcutaneous fat. SG involvement is a rare manifestation during sarcoidosis, and the presence of non-caseating granulomas needs to be differentiated from granulomas of other etiology. This review article provides an overview of normal and pathological SGs in the context of rheumatic diseases, identifying key elements in the tissue as diagnostic and prognostic biomarkers, useful in the current clinical practice.
29657217 Systemic lupus erythematosus with Sjögren's syndrome and renal tubular acidosis presentin 2018 Mar Systemic lupus erythematosus (SLE) presenting as diabetes insipidus (DI) is a rare association; there is a case report of neurogenic DI in patients of SLE; however, SLE and nephrogenic DI has not been reported in literature. We present a case of SLE presenting as nephrogenic DI. We report a case who presented with DI (nephrogenic) and fulfilled criteria for SLE and Sjögren's syndrome with renal tubular acidosis.
30874247 Effects of Tocilizumab Therapy on Serum Interleukin-33 and Interleukin-6 Levels in Patient 2018 Dec OBJECTIVES: This study aims to examine the effects of tocilizumab therapy on serum levels of interleukin (IL)-33 and IL-6 in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: Interleukin-33 and IL-6 levels in serum samples from 83 RA patients (10 males, 73 females; mean age 51.9 years; range, 26 to 77 years) and 12 healthy controls (2 males, 10 females; mean age 52.2 years; range, 39 to 62 years) were compared by cross-sectional, case control analysis. Of the RA patients, 40 received 24 weeks of tocilizumab therapy and were assigned to the prospective cohort. These 40 patients were then divided into two subgroups as responders and non-responders according to the American College of Rheumatology (ACR) 20. The remaining 43 RA patients did not receive tocilizumab therapy. Serum cytokine levels were analyzed at baseline and after 24 weeks of tocilizumab therapy in these patients. RESULTS: Interleukin-33 and IL-6 concentrations were significantly higher in RA patients than in healthy controls (p<0.001 for both). Serum IL-33 levels in RA patients showed a significant correlation with rheumatoid factor titer (r=0.660, p<0.001), and IL-6 levels showed a significant correlation with high-sensitivity C-reactive protein levels (Spearman's rank correlation coefficient=0.482, p<0.001). Serum IL-33 levels decreased significantly after 24 weeks of tocilizumab therapy (p<0.001); this was particularly marked in ACR20 responders (p<0.001). However, the decrease in non-responders was not significant (p=0.066). Changes in serum IL-6 levels after 24 weeks of tocilizumab therapy were not significant in either ACR20 responders or non-responders. CONCLUSION: Serum IL-33 levels in RA patients receiving tocilizumab therapy decreased significantly, particularly in ACR20 responders. Thus, IL-33 may be a useful marker for monitoring responses to tocilizumab therapy.