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ID PMID Title PublicationDate abstract
29852454 The combination of FK506 and an anti-CD147 mAb exerts potential therapeutic effects on a m 2018 Sep Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and excessive T lymphocyte activation plays a critical role in the development of inflammation. CD147 is an antigen related to T cell activation, CD147 blockade exerts beneficial effects on RA. FK506, also known as tacrolimus, exerts strong immunosuppressive effects by inhibiting T cell activation. In this study, RL73 (an anti-mouse CD147 functional-grade purified antibody) and FK506 were co-administered to mice with collagen-induced arthritis (CIA). As expected, the combination of these two drugs produced superior therapeutic effects than either drug alone and enabled the administration of each drug at a lower dose. Moreover, joint damage and destruction were significantly improved in mice injected with both FK506 and RL73 compared with mice injected with either agent alone. These effects might have been observed because the proportions of CD4 + T and CD8 + T cells in the mouse spleen of the combination regimen were clearly decreased compared with each monotherapy. In addition, the proportions of Th2 subsets in the mouse spleen and peripheral blood were clearly increased, and the serum levels of the cytokines interleukin 4 (IL-4) and IL-10 were markedly increased in mice treated with the combination therapy compared with the other groups of mice. The splenic total number of T lymphocytes also showed that the inhibition of T lymphocytes was the most obvious in the combined treatment group. Based on the results from the present study, combining FK506 and the anti-CD147 mAb might be a new practical therapeutic option for the treatment of RA.
30572137 Novel Sjögren's autoantibodies found in fibromyalgia patients with sicca and/or xerostomi 2019 Feb INTRODUCTION: A significant proportion of patients with fibromyalgia (FM) complain of dry eyes and mouth. Many Sjögren's syndrome (SS) patients also complain of FM symptoms, and there is literature that suggests that there is interplay between these two disorders. Recently, the presence of novel tissue specific autoantibodies (TSAs), SP-1, CA6, and PSP, has been observed in the early stages of SS. These early markers present themselves before the classic autoantibodies, such as SS-A/Ro, SS-B/La, ANA, and RF. OBJECTIVE: This study aims to examine the relationship between SS and FM by testing patients with FM who also complain of xerostomia and sicca symptoms, for SS- related biomarkers. METHODS: A cohort of 185 patients who met both the 1990 and 2010 preliminary diagnostic criteria for FM and who admitted to symptoms of sicca and/or xerostomia were selected for this study. Serum from 151 study patients was sent to a tertiary lab, Immco Diagnostics, for testing of the classic autoantibodies (SS-A/Ro, SS-B/La, ANA and RF) and TSAs (SP-1, CA6, PSP), while the rest (34 patients) were tested for TSAs only. RESULTS: Of the 151 patients who were evaluated for both the early and classic SS markers, 49 (32%) tested positive for SS autoantibodies. Of those, 4 (3%) tested positive for the classic SS markers only, 40 (26%) of the patients tested positive for the early SS markers only, and 5 (3%) tested positive for both the early and classic SS markers. Of the 34 patients who were tested for early SS markers only, 10 (29%) tested positive and 24 (71%) tested negative. Further analysis of all the patients that tested positive for the TSAs (n = 55), found 83.6% (46) were positive for SP-1, 12.7% (7) were positive for CA6 and 20.0% (11) were positive for PSP. 85.5% (47) of these patients were positive for only one of the TSAs and 14.5% (8) were positive for more than one TSA. CONCLUSION: Approximately 1/3 of FM patients that were tested for both the TSAs and classic Sjögren's markers tested positive for a SS biomarker, and the majority of those patients tested positive for one or more of the TSAs. This suggests that autoimmunity, specifically early- stage Sjögren's syndrome, may be involved in the pathophysiology of fibromyalgia.
29191572 Th17 cells in primary Sjögren's syndrome: Pathogenicity and plasticity. 2018 Feb Th17 cells play an important physiological role at mucosal barriers, and are involved in inflammatory responses to pathogens. Th17 cells and their signature cytokine IL-17 are also present in salivary gland lesions of primary Sjögren's syndrome (pSS) patients and can be elevated in their peripheral blood. In pSS patients, clear correlations between increased Th17 cell activity and symptoms of the disease have not been found, but Th17 cells may contribute to disease progression, for example by supporting autoreactive B cell responses. In mouse models of pSS, Th17 cells play an important role in pathogenesis, particularly at disease onset, when there is a disturbed balance between T effector and T regulatory cells. Studying the pathogenicity of Th17 cells in humans is complicated due to the plasticity of this cell subset, allowing them to obtain different effector functions depending on the local environment. Th17 cells can develop towards Th17.1 cells, producing both IL-17 and IFN-γ, or even towards Th1-like cells producing IFN-γ in the absence of IL-17. These effector subsets may be more pathogenic than bona fide Th17 cells. Co-expression of IFN-γ by Th17 cells has been shown to promote chronic inflammation in several autoimmune diseases and may also contribute to pSS pathogenesis. In line with the noticeable role of IL-17 in pSS mouse models, interference with Th17 cell generation, recruitment or effector functions (e.g. IL-17 inhibition) can prevent or ameliorate disease in these models. Therapies targeting Th17 cells or IL-17 have not been tested so far in pSS patients, although treatment with rituximab seems to lower local and systemic IL-17 protein levels, and to a lesser extent also chemokine receptor-defined Th17 cells. In this review we discuss current knowledge of pathogenicity and plasticity of Th17 cells in human pSS and murine models of pSS. We postulate that plasticity towards Th17.1 cells in pSS may enhance pathogenicity of Th17 cells at the main target sites of the disease, i.e. salivary and lacrimal glands.
29782688 Oral yeast colonization in patients with primary and secondary Sjögren's syndrome. 2018 Oct OBJECTIVE: The study aimed to investigate the pattern of oral yeast colonization of Sjögren's syndrome patients and its correlation to salivary flow rates, age, and time of the disease progression. MATERIALS AND METHODS: Saliva and swab specimens were obtained from 45 patients (primary Sjögren's syndrome = 15/ secondary Sjögren's syndrome = 15/ healthy controls = 15). Yeast species were identified using culture method through chromogenic medium followed by polymerase chain reaction and Sanger sequencing. RESULTS: Eleven species from six different genera were detected. The most prevalent species found was Candida albicans followed by Candida tropicalis, Candida glabrata, Candida parapsilosis, and Candida krusei. Both groups of Sjögren's syndrome showed higher counts of C. albicans (Total and CFU counts) when compared to control group. In contrast, a greater variety of yeast species was identified on samples of the control group. CONCLUSIONS: This study showed that C. albicans is the most prevalent yeast, but also that a variety of other yeast species can colonize the oral cavity of Sjogren's syndrome patients. The identification of most of the colonies was not obtained by culturing-PCR methods combined.
30013261 Sjögren's and plasma cell variant Castleman disease: a case report. 2018 Mar Castleman disease is a rare cause of lymphoid hyperplasia and may result in localized symptoms or an aggressive, multisystem disorder. It can mimic other diseases like lymphoma or tuberculosis. It classically presents as a mediastinal mass that involves the lymphatic tissue primarily but can also affect extra lymphatic sites including the lungs, larynx, parotid glands, pancreas, meninges, and muscles. In HIV and HHV8-negative patients with idiopathic multi-centric Castleman disease, pathogenesis may involve autoimmune mechanisms. We highlight and report a case of a 34-year-old Ghanaian female who was successfully diagnosed and managed for Sjögren's as well as plasma cell variant Castleman disease with combination chemotherapy and rituximab followed by eighteen months maintenance therapy with pulse chlorambucil and prednisolone and three monthly rituximab.
29854827 How to Distinguish Patients with pSS among Individuals with Dryness without Invasive Diagn 2018 In the course of pSS, inflammatory cell infiltration consists mainly of lymphocytes infiltrating exocrine glands, which leads to their impaired function. The characteristic feature is generalized dryness. The aim of this study was to attempt to answer the question whether it is possible to distinguish between patients with pSS and individuals with dryness caused by other pathologies without applying invasive studies. The study included 68 patients with pSS and 43 healthy controls with dryness. FS ≥ 1 was observed in 90% of patients with pSS (with or without dryness), and only in 23% of the control group (only with xerostomia). In the pSS group, anaemia (p = 0.0085), lymphocytopenia (p = 0.0006), elevated ERS (p = 0.001), higher RF titer, and ANA antibodies were noted. Configuration of anti-SSA + SSB + Ro52 antibodies was characteristic for the pSS group. Considering the clinical symptoms, statistically significant differences were noted between pSS patients and the control group in frequency (p = 0.02) and severity (p = 0.042) of fatigue, lymphadenopathy, major salivary gland involvement, and photosensitivity to UV light. In conclusion, invasive methods are pivotal in pSS diagnosis in this salivary gland biopsy. Chronic fatigue syndrome is more common in pSS patients and can be subjective distinguishing factor in the group of people with dryness.
29434340 Glucocorticoid receptor expression in resident and hematopoietic cells in IgG4-related dis 2018 Jun Immunoglobulin G4-related disease is a rare immune-mediated disease characterized by the infiltration of IgG4-positive plasma cells and unique storiform fibrosis of multiple organs. The majority of IgG4-related disease patients respond to glucocorticoids, yet the precise mechanism of their action remains unclear. Pathological sections of the submaxillary gland, kidney, and retroperitoneum from 20 patients in total diagnosed with IgG4-related disease were analyzed for glucocorticoid receptor expression and the cell types expressing glucocorticoid receptor. Strong and abundant expression of glucocorticoid receptor was observed in the submaxillary gland, kidney, and retroperitoneum of IgG4-related disease patients, while glucocorticoid receptor was rarely or only faintly observed in the submaxillary gland of patients with Sjögren's syndrome, radicular cysts and sialolithiasis or in the healthy kidney. Glucocorticoid receptor was mainly expressed in fibro/myofibroblasts, CD4-positive T cells and IgG4-positive plasma cells in the submandibular glands and kidneys of IgG4-related disease patients. The abundant expression of glucocorticoid receptor in various types of cells, including resident fibro/myofibroblasts in IgG4-related disease patients might provide clues to the mechanism of steroid responsiveness in IgG4-related disease patients.
29310446 Resting-state fMRI in primary Sjögren syndrome. 2018 Sep Background The involvement of the central nervous system in primary Sjögren syndrome (pSS) remains controversial. Functional magnetic resonance imaging (fMRI) is a relatively new method that can be applied to investigate the heterogeneity of central nervous system (CNS) involvement in pSS patients through regional homogeneity (ReHo) analysis. Purpose To collect data from pSS patients and healthy controls, and use ReHo analysis to elucidate the neurobiological mechanism of CNS involvement in pSS. Material and Methods Fourteen clinically diagnosed pSS patients and 14 age- and gender-matched healthy controls underwent resting-state fMRI. The data were processed by ReHo analysis. The double sample t-test was used to compare ReHo data between groups. Results Compared to controls, pSS patients had significantly increased ReHo values in the right cerebrum, left limbic lobe, right middle temporal gyrus, and the inferior parietal lobe. However, ReHo values significantly decreased in the right lingual gyrus, left cuneiform lobe, left superior occipital gyrus, bilateral middle occipital gyrus, and the fronto-parietal junction area ( P < 0.01, clusters ≥ 50 voxels). Conclusion This study demonstrates the abnormal brain activity in the visual cortex and fronto-parietal junction area in pSS patients, suggesting pathological neuronal dysfunction in these regions.
29231165 Polyvalent immunoglobulins with vitamin D3 and vitamin B12 in the treatment of Sjogren's s 2018 Jan BACKGROUND: Sjogren's syndrome, involving sicca symptoms with xerostomia, stomatitis, and considerable pain is a difficult-to-treat autoimmune disease where the treatment options are limited and, as in the case of methotrexate, have a low therapeutic index. CASE REPORT: This case report concerns a male patient, aged 75 years and vegetarian, with Sjogren's syndrome subsequently confirmed by salivary gland biopsy. Serum antinuclear antibodies (ANA) were elevated (1 : 320). Low serum vitamin B12 and iron levels could be improved after 20 days using vitamin B12 and iron oral supplements. Despite symptomatic treatment, xerostomia, glossitis, and glossodynia were still present, at times marked, after 12 months when the ANA titer was unchanged. Following treatment with an anti-inflammatory polyvalent immunoglobulin formulation (Lactobin®N, 7 g daily), a bovine colostrum concentrate given orally in combination with oral vitamin D3 (2,000 IU daily), sicca symptoms and xerostomia progressively decreased and at day 750 were confined to occasional and minor glossitis of the upper lip. CONCLUSION: This case report demonstrates the satisfactory control of Sjogren's syndrome using oral polyvalent immunoglobulins with vitamin D3. In contrast to treatment options involving antimalarial drugs and methotrexate, there are no safety issues in patients tolerant to milk products.
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29154979 Small fiber neuropathy: Diagnosis, causes, and treatment. 2018 Oct Small fiber neuropathy, which affects the sensory Aδ and C fibers, is now a major diagnostic and therapeutic challenge. Nearly 7% of the general population have chronic neuropathic pain responsible for severe quality-of-life impairments. Awareness must therefore be raised among clinicians of the somatosensory and autonomic symptoms that can reveal small fiber neuropathy, appropriate diagnostic investigations, most common causes, and best treatment options for each patient profile. To help achieve this goal, the present review article discusses the clinical presentation of neuropathic pain and paresthesia and/or autonomic dysfunction due to involvement of nerves supplying exocrine glands and smooth muscle; normal findings from standard electrophysiological investigations; most informative diagnostic tests (epidermal nerve fiber density in a skin biopsy, laser-evoked potentials, heat- and cold-detection thresholds, electrochemical skin conductance); main causes, which consist chiefly of metabolic diseases (diabetes mellitus, glucose intolerance), dysimmunity syndromes (Sjögren's syndrome, sarcoidosis, monoclonal gammopathy), and genetic abnormalities (familial amyloidosis due to a transthyretin mutation, Fabry disease, sodium channel diseases); and the available symptomatic and etiological treatments.
30272305 Oral microbial flora of patients with Sicca syndrome. 2018 Dec Primary sicca syndrome (pSS) is a systemic autoimmune disease. However, its exact etiology and pathogenesis remain elusive. Various infectious factors have been identified to be closely associated with the occurrence and development of PSS. The present study aimed to assess the composition of the oral microbial flora of patients with pSS in China in order to provide guidance for treatment. The microbial flora of nine patients with pSS and five healthy controls from East China was evaluated in saliva samples using high‑throughput sequencing. A high microbial diversity was detected in the pSS and control groups, with bacteroidetes, firmicutes and proteobacteria constituting the largest phyla in the two groups. Compared with the control group, bacteroidetes and actinobacteria were significantly more abundant in the pSS group, whereas proteobacteria were significantly less abundant. However, no significant differences in bacterial richness and diversity were observed between the two groups. According to a Kyoto Encyclopedia of Genes and Genomes linear discriminant analysis, genes regulating cell apoptosis and the immune and digestive systems were significantly upregulated in the pSS group compared with those in the control group. In conclusion, the present study provided basic data on the flora of the oral cavity in patients with pSS from East China and may serve as a reference for the treatment of this condition.
30374004 [Bone and calcium metabolism associated with malignancy. Paraneoplastic rheumatologic musc 2018 Patients with malignant tumors may present with joint pain or arthritis(paraneoplastic arthritis). It needs to be carefully determined whether these symptoms are related to the malignant tumor, due to a concomitant rheumatoid disease, due to an adverse reaction to treatment, or due to a relapse. It can be relatively easy to diagnose paraneoplastic syndrome when there is clearly a malignant tumor present or typical symptoms are exhibited. However, clinicians should be aware that these paraneoplastic syndrome phenomena can occur before the malignant tumor is diagnosed. An occult malignancy should be suspected when a patient is elderly and exhibits atypical clinical symptoms of a rheumatic disease;is poorly responsive to usual treatment;or has general symptoms such as weight loss or exhibits suggestive physical findings. In particular, hematological malignancies require careful observations as they do not surface quickly.
30336338 Dihydroartemisinin derivative DC32 attenuates collagen-induced arthritis in mice by restor 2018 Dec Imbalance of Treg/Th17 and chronic synovitis characterized by the recruitment and infiltration of inflammatory cells are the typical features of rheumatoid arthritis (RA). IL-6 promotes the differentiation and function of Th17 cells, which contributes to the imbalance of Treg/Th17 and aggravates lymphocytic infiltration in joints. DC32, a dihydroartemisinin derivative, was found to have anti-inflammatory and immunosuppressive activities in previous study. The aim of this study is to evaluate the effects and mechanisms of DC32 in immunodeficiency and inflammatory infiltration of RA. In vivo, the antirheumatic effect of DC32 was evaluated in a collagen-induced arthritis (CIA) mouse model in DBA/1 mice. The percentages of Treg and Th17 and transcription of IL-6 in the spleen were assayed. In vitro, a coculture system of ConA-activated lymphocytes and fibroblast-like synoviocytes (FLSs) from rat with adjuvant arthritis (AA) was established. The effects and mechanisms of DC32 on synovitis were investigated. It was shown that DC32 inhibited footpad swelling and lymphocytic infiltration in mice with CIA and significantly restored the Treg/Th17 balance by reducing the transcription of IL-6 in splenocytes. DC32 significantly inhibited the lymphocyte-induced invasion and migration of FLSs by decreasing the secretion of MMPs (MMP-2, MMP-3) in vitro. DC32 also reduced the transcription of chemokines (CXCL12, CX3CL1) and IL-6 in FLSs, as well as IL-6 levels in the supernatant. These results demonstrated that DC32 may attenuate RA by restoring Treg/Th17 balance and inhibiting lymphocytic infiltration through downregulation of the expression and transcription of IL-6. This study supports the potential of DC32 to down-regulate IL-6 for the treatment of RA and other related autoimmune diseases.
30428612 Non-Hepatic Alkaline Phosphatase, hs-CRP and Progression of Vertebral Fracture in Patients 2018 Nov 13 BACKGROUND: Interactions and early warning effects of non-hepatic alkaline phosphatase (NHALP) and high-sensitivity C-reactive protein (hs-CRP) on the progression of vertebral fractures (VFs) in patients with rheumatoid arthritis (RA) remain unclear. We aim to explore whether serum concentrations of NHALP and hs-CRP could serve as a promising dual biomarker for prognostic assessment of VF progression. METHODS: Unadjusted and adjusted hazard ratios (aHRs) of VF progression were calculated for different categories of serum NHALP and hs-CRP using the Cox regression model in RA patients. The modification effect between serum NHALP and hs-CRP on VF progression was determined using an interaction product term. RESULTS: During 4489 person-years of follow-up, higher NHALP (>125 U/L) and hs-CRP (>3.0 mg/L) were robustly associated with incremental risks of VF progression in RA patients (aHR: 2.2 (95% confidence intervals (CIs): 1.2⁻3.9) and 2.0 (95% CI: 1.3⁻3.3) compared to the lowest HR category, respectively). The interaction between NHALP and hs-CRP on VF progression was statistically significant (p < 0.05). In the stratified analysis, patients with combined highest NHALP and hs-CRP had the greatest risk of VF progression (aHR: 4.9 (95% CI: 2.5⁻9.6)) compared to the lowest HR group (NHALP < 90 U/L and hs-CRP < 1 mg/L). CONCLUSIONS: In light of underdiagnoses of VFs and misleading diagnosis by single test, NHALP and hs-CRP could serve as compensatory biomarkers to predict subclinical VF progression in RA patients.
29288368 Single nucleotide polymorphism of Methyl-CpG-binding protein 2 gene associates with juveni 2018 Feb Methyl-CpG-binding protein 2 (MeCP2) is a transcription suppressor or activator, acting through binding to methylated DNA. Numerous investigations have established a role for methylation aberrancies in the pathogenesis of autoimmune disorders. Single nucleotide polymorphisms (SNPs) in MECP2 gene have been implicated with susceptibility to rheumatoid arthritis (RA). Here, the plausible association of MECP2 gene polymorphisms was evaluated with juvenile idiopathic arthritis (JIA) predisposition in Iranian pediatric patients. In this case-control association study, 49 JIA patients and 398 age-, sex-, and ethnicity-matched healthy individuals were included. Genotyping of all samples for MECP2 gene rs1734787, rs1734791, rs1734792, and rs17435 polymorphisms was conducted by real-time allelic discrimination PCR technique. Except the AT genotype of rs17435 SNP, none of the alleles and genotypes of other positions were distributed significantly between JIA cases and controls. AT genotype was less frequent in JIA cases and was found to be protective genotype of JIA proneness (OR = 0.42; CI, 0.19-0.90; P = 0.028). Among the haplotypes, CCAA and TTTT were detected to have significant difference between cases and controls (OR = 1.74; CI, 1.01-2.98; P = 0.042 and OR = 1.82; CI, 1.05-3.13; P = 0.028). All positions were in linkage disequilibrium with each other according to D'. MECP2 gene rs17435 polymorphism was associated with JIA predisposition. Considering the involvement of genetic polymorphisms of MECP2 gene in susceptibility to adult-onset RA, this gene might basically play a role in the initiation of arthritis during early stages of life.
27456855 Prevalence and predictors of hand involvement in Thai patients with systemic sclerosis. 2018 Jan AIM: Data regarding the clinical and radiographic hand involvement in Asian patients with systemic sclerosis (SSc) are limited. Thus, we determined the prevalence of clinical and radiographic hand involvement in Thai SSc patients, comparing diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc). We also determined the factors associated with arthritis, contracture of fingers and digital ulcers. METHOD: SSc patients seen at the Rheumatology Clinic, Chiang Mai University, Thailand, from December 2012 to June 2013 were consecutively invited to enroll in the study. After study entry, demographic data, clinical features and hand radiographs were evaluated. RESULT: We studied 110 SSc patients (73 dcSSc) with mean ± SD age of 53.2 ± 9.2 years and disease duration from non-Raynaud's phenomenon of 4.9 ± 4.8 years. The prevalence of arthritis, finger contractures and digital ulcers were 10 (9.1%), 47 (42.7%), and 14 (12.7%), respectively. DcSSc patients had significantly more of the following hand complications than lcSSc patients: digital pitting scar (53.4% vs. 27.0%, P = 0.008), digital ulcer (17.8% vs. 2.7%, P = 0.032), traumatic ulcer (27.4% vs. 0%, P < 0.001), acrolysis (45.2% vs. 18.9%, P = 0.007) and flexion contracture (60.3% vs. 8.1%, P < 0.001). Radiographic finger contractures were more prevalent in the dcSSc subset. In multivariate logistic regression analysis, a positive rheumatoid factor was associated with arthritis; dcSSc, arthritis and modified Rodnan skin score (MRSS) > 18 were associated with contracture of fingers. Furthermore, hand MRSS > 4 was associated with digital ulcers. CONCLUSION: Our results confirm that dcSSc patients had more severe clinical hand complications than lcSSc. However, radiographic findings were similar among subgroups, except that more finger contractures were seen in dcSSc. Finally, the presence of rheumatoid factor is associated with arthritis, and high MRSS is associated with finger contractures and digital ulcers.
29764485 The role of inflammation in the development of epilepsy. 2018 May 15 Epilepsy, a neurological disease characterized by recurrent seizures, is often associated with a history of previous lesions in the nervous system. Impaired regulation of the activation and resolution of inflammatory cells and molecules in the injured neuronal tissue is a critical factor to the development of epilepsy. However, it is still unclear as to how that unbalanced regulation of inflammation contributes to epilepsy. Therefore, one of the goals in epilepsy research is to identify and elucidate the interconnected inflammatory pathways in systemic and neurological disorders that may further develop epilepsy progression. In this paper, inflammatory molecules, in neurological and systemic disorders (rheumatoid arthritis, Crohn's, Type I Diabetes, etc.) that could contribute to epilepsy development, are reviewed.Understanding the neurobiology of inflammation in epileptogenesis will contribute to the development of new biomarkers for better screening of patients at risk for epilepsy and new therapeutic targets for both prophylaxis and treatment of epilepsy.
29982962 Novel Anti-arthritic Mechanisms of Polydatin in Complete Freund's Adjuvant-Induced Arthrit 2018 Oct Articular manifestations are the main hall mark for rheumatoid arthritis; inflammation and oxidative stress are involved in its pathogenesis. This study was designed to figure out the possible therapeutic potential of polydatin on experimentally induced arthritis in rats. Polydatin (POLY) was administered (200 mg/kg, p.o.) for 21 days to complete Freund's adjuvant (CFA; 0.1 ml, s.c.)-induced arthritic rats. Meanwhile, methotrexate (MTX; 0.75 mg/kg, i.p.) was given as a reference standard disease-modifying anti-rheumatic drug (DMARD). Both POLY and MTX significantly attenuated articular damage associated with CFA-induced arthritis. This was manifested by reducing levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), and matrix metalloproteinase-3 (MMP-3), paralleled with marked decrease in hind paw and ankle diameters. Moreover, POLY and MTX downregulated gene expressions of receptor activator of nuclear factor kappa-B ligand (RANKL) as well as signal transducer and activator of transcription-3 (STAT3) besides hampering immunohistochemical staining of vascular endothelial growth factor (VEGF) and nuclear factor kappa-B (NF-κB). Furthermore, substantial decline in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level associated with significant rise in reduced glutathione content (GSH) was observed. These findings provide an innovative therapeutic approach of POLY as a natural anti-arthritic drug through modulating IL-6/STAT-3/IL-17/NF-кB cascade. Graphical Abstract ᅟ.
29195024 Tuberculosis Risk in Ankylosing Spondylitis, Other Spondyloarthritis, and Psoriatic Arthri 2018 Oct OBJECTIVE: Rheumatoid arthritis is a risk factor for tuberculosis (TB), particularly following treatment with biologic agents. Since these therapies are increasingly used in ankylosing spondylitis (AS), other types of spondyloarthritis (SpA), and psoriatic arthritis (PsA), we investigated the corresponding TB risks in these patients. METHODS: We identified individuals with AS/SpA/PsA, and non-AS/SpA/PsA comparators by linking Swedish national patient, population, TB, and rheumatology registers, and followed them for TB occurrence. Incidence rates were estimated for biologic-naive and biologic-exposed patients and the comparators. We calculated hazard ratios (HRs), adjusted for age, sex, and country of birth. RESULTS: Included in this study were 38,702 patients with AS/SpA/PsA, and 200,417 persons from the general population. Among the patients, 11 active TB cases were identified, with an incidence rate (per 10(5) ) of 22 (95% confidence interval [95% CI] 8.3-59.2) for biologic-exposed patients, 2.7 (95% CI 1.3-5.6) for biologic-naive patients, and 2.4 (95% CI 1.8-3.3) for non-AS/SpA/PsA comparators. The adjusted HR comparing biologic-naive patients to the general population was 1.2 (95% CI 0.5-2.7), and 7.5 (95% CI 1.9-29) comparing biologic-exposed to biologic-naive patients. CONCLUSION: Biologic-naive AS/SpA/PsA patients are not at an increased TB risk in Sweden. Following treatment with biologic agents, the risk increased, but the absolute TB risk was low.
29298172 Psoriatic Arthritis in Nigeria: Case Series and Literature Review. 2018 Jun BACKGROUND: Psoriatic arthritis (PsA) is an extracutaneous manifestation of psoriasis occurring in 6% to 42% of patients. Both conditions are common among whites but rarely reported among black Africans.Few African studies, however, have reported PsA frequencies of 0% to 4.6%, with a previous case report of 2 patients from a Nigerian rheumatology clinic. METHODS: Case records of PsA patients from the Lagos State University Teaching Hospital Rheumatology Clinic seen over a 5-year period from January 2012 to December 2016 were retrieved and documented.Psoriatic arthritis was diagnosed using the Classification Criteria for Psoriatic Arthritis. Data on demography, clinical features, laboratory parameters, imaging, and treatment were extracted from case records. RESULTS: Twelve PsA cases were identified out of 2330 patients (0.5%) seen during the study period. There were 9 males and 3 females. Age range was 24 to 67 years (mean, 45.3 ± 15.1 years). Duration of psoriasis ranged between 11 and 96 months (mean, 46.8 ± 33.6 months), whereas median duration of arthritis at presentation was 15 months (range, 4-72 months).Oligoarthritis was the commonest presentation (58.3%). Dactylitis (66.7%) and enthesitis (44.7%) were frequent extra-articular features. All patients were negative for rheumatoid factor and human immunodeficiency virus. HLAB27 was negative in 5 patients tested.Treatment was mostly with nonsteroidal anti-inflammatory drugs (100%) and methotrexate (75%). Only 1 patient received the biologic etanercept. Eight subjects (66.6%) showed initial improvement in skin and joint symptoms, of which 6 had a relapse within 6 to 12 months. CONCLUSIONS: Psoriatic arthritis is rare among Nigerians and predominantly affects males in their fourth decade. Oligoarthritis is common, and extra-articular manifestations are frequent.