Browse

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

ID PMID Title PublicationDate abstract
31861827 A Clinical Approach for the Use of VIP Axis in Inflammatory and Autoimmune Diseases. 2019 Dec 20 The neuroendocrine and immune systems are coordinated to maintain the homeostasis of the organism, generating bidirectional communication through shared mediators and receptors. Vasoactive intestinal peptide (VIP) is the paradigm of an endogenous neuropeptide produced by neurons and endocrine and immune cells, involved in the control of both innate and adaptive immune responses. Exogenous administration of VIP exerts therapeutic effects in models of autoimmune/inflammatory diseases mediated by G-protein-coupled receptors (VPAC1 and VPAC2). Currently, there are no curative therapies for inflammatory and autoimmune diseases, and patients present complex diagnostic, therapeutic, and prognostic problems in daily clinical practice due to their heterogeneous nature. This review focuses on the biology of VIP and VIP receptor signaling, as well as its protective effects as an immunomodulatory factor. Recent progress in improving the stability, selectivity, and effectiveness of VIP/receptors analogues and new routes of administration are highlighted, as well as important advances in their use as biomarkers, contributing to their potential application in precision medicine. On the 50th anniversary of VIP's discovery, this review presents a spectrum of potential clinical benefits applied to inflammatory and autoimmune diseases.
30863888 Assessing acrolein for determination of the severity of brain stroke, dementia, renal fail 2020 Feb It was found recently that acrolein (CH(2)=CH-CHO), mainly produced from spermine, is more toxic than ROS (reactive oxygen species, O(2)(-·), H(2)O(2), and ·OH). In this review, we describe how the seriousness of brain infarction, dementia, renal failure, and Sjӧgren's syndrome is correlated with acrolein. In brain infarction and dementia, it was possible to identify incipient patients with high sensitivity and specificity by measuring protein-conjugated acrolein (PC-Acro) in plasma together with IL-6 and CRP in brain infarction and Aβ(40/42) in dementia. The level of PC-Acro in plasma and saliva correlated with the seriousness of renal failure and Sjӧgren's syndrome, respectively. Thus, development of acrolein scavenger medicines containing SH-group such as N-acetylcysteine derivatives is important to maintain QOL (quality of life) of the elderly.
31770250 Gastric mucormycosis complicated by a gastropleural fistula: A case report and review of t 2019 Nov RATIONALE: Mucormycosis is a rare opportunistic fungal infection with poor prognosis. The incidence of mucormycosis has been increasing, and it is a threat to immunocompromised hosts. We present a case of gastric mucormycosis complicated by a gastropleural fistula during immunosuppressive treatment for adult-onset Still disease (AOSD). PATIENT CONCERNS: An 82-year-old woman diagnosed with AOSD who developed gastric ulcers during the administration of an immunosuppressive therapy with corticosteroids, cyclosporine, and tocilizumab complained of melena and epigastralgia. Esophagogastroduodenoscopy showed multiple ulcers covered with grayish or greenish exudates. DIAGNOSES: The patient diagnosed with mucormycosis based on culture and biopsy of the ulcers, which showed nonseptate hyphae branching at wide angles. Mucor indicus was identified using polymerase chain reaction. INTERVENTIONS AND OUTCOMES: Although liposomal amphotericin B was administered, gastric mucormycosis was found to be complicated by a gastropleural fistula. The patient died because of pneumonia due to cytomegalovirus infection, and autopsy revealed the presence of Mucorales around the fistula connecting the stomach and diaphragm. LESSONS: Gastric mucormycosis is refractory to treatment and fatal. Surgical resection, if possible, along with antifungal drugs can result in better outcomes.
31683641 Invariant NKT Cells and Rheumatic Disease: Focus on Primary Sjogren Syndrome. 2019 Oct 31 Primary Sjogren syndrome (pSS) is a complex autoimmune disease mainly affecting salivary and lacrimal glands. Several factors contribute to pSS pathogenesis; in particular, innate immunity seems to play a key role in disease etiology. Invariant natural killer (NK) T cells (iNKT) are a T-cell subset able to recognize glycolipid antigens. Their function remains unclear, but studies have pointed out their ability to modulate the immune system through the promotion of specific cytokine milieu. In this review, we discussed the possible role of iNKT in pSS development, as well as their implications as future markers of disease activity.
30759717 MIST1, an Inductive Signal for Salivary Amylase in Mesenchymal Stem Cells. 2019 Feb 12 Sjögren's syndrome (SjS) is an autoimmune disease that destroys the salivary glands and results in severe dry mouth. Mesenchymal stem cell (MSC) transplantation has been recently proposed as a promising therapy for restoring cells in multiple degenerative diseases. We have recently utilized advanced proteomics biochemical assays to identify the key molecules involved in the mesenchymal-epithelial transition (MET) of co-cultured mouse bone-marrow-derived MSCs mMSCs with primary salivary gland cells. Among the multiple transcription factors (TFs) that were differentially expressed, two major TFs were selected: muscle, intestine, and stomach expression-1 (MIST1) and transcription factor E2a (TCF3). These factors were assessed in the current study for their ability to drive the expression of acinar cell marker, alpha-salivary amylase 1 (AMY1), and ductal cell marker, cytokeratin19 (CK19), in vitro. Overexpression of MIST1-induced AMY1 expression while it had little effect on CK19 expression. In contrast, TCF3 induced neither of those cellular markers. Furthermore, we have identified that mMSCs express muscarinic-type 3 receptor (M3R) mainly in the cytoplasm and aquaporin 5 (AQP5) in the nucleus. While MIST1 did not alter M3R levels in mMSCs, a TCF3 overexpression downregulated M3R expressions in mMSCs. The mechanisms for such differential regulation of glandular markers by these TFs warrant further investigation.
31788032 Fasting triglycerides and glucose index: a useful screening test for assessing insulin res 2019 BACKGROUND: Insulin resistance (IR) is frequently observed in patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). In clinical practice, IR assessment is limited to a low proportion of patients due to cost and equipment and technical expertise requirements. The surrogate index of triglycerides and glucose (TyG index) has been validated in non-rheumatic populations, showing adequate sensitivity and specificity for IR, although this index has not yet been used in connective tissue disorders. The aim of this study was to evaluate the frequency of insulin resistance (IR) using the validated surrogate index of triglycerides and glucose (TyG index) and to explore factors associated with IR in Mexican women with RA or SLE. METHODS: Ninety-five female RA and 57 SLE patients were included in a cross-sectional study. Clinical and epidemiological variables were evaluated. IR was assessed using the TyG index with a cutoff value of > 4.68. Logistic regression analysis was performed to identify factors associated with IR excluding confounders. RESULTS: IR frequency in the entire sample was 50%, higher than the 10% observed in non-rheumatic controls (p < 0.001). The frequency of IR was similar in SLE (49.1%) and RA (50.5%, p = 0.8) patients. IR was associated with a longer duration of hypertension and higher total cholesterol and low density lipoprotein cholesterol levels. Based on multivariate analysis, the duration of hypertension (OR: 1.06; 95% CI 1.002-1.12, p = 0.04), waist circumference (OR: 1.04; 95% CI 1.01-1.08, p = 0.007), uric acid levels (OR: 1.46; 95% CI 1.08-1.97, p = 0.01), RA (OR: 4.87; 95% CI 1.31-18.78, p = 0.01) and SLE (OR: 4.22; 95% CI 1.06-16.74, p = 0.04) were the main risk factors for IR. CONCLUSIONS: This study shows that the TyG index is a useful screening test for IR in RA and SLE patients. Future longitudinal studies should be performed with the aim of identifying the predictive value of TyG index results for identifying complications linked to IR.
30769926 Innate Immune Modulation by GM-CSF and IL-3 in Health and Disease. 2019 Feb 15 Granulocyte-macrophage colony-stimulating factor (GM-CSF) and inteleukin-3 (IL-3) have long been known as mediators of emergency myelopoiesis, but recent evidence has highlighted their critical role in modulating innate immune effector functions in mice and humans. This new wealth of knowledge has uncovered novel aspects of the pathogenesis of a range of disorders, including infectious, neoplastic, autoimmune, allergic and cardiovascular diseases. Consequently, GM-CSF and IL-3 are now being investigated as therapeutic targets for some of these disorders, and some phase I/II clinical trials are already showing promising results. There is also pre-clinical and clinical evidence that GM-CSF can be an effective immunostimulatory agent when being combined with anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) in patients with metastatic melanoma as well as in novel cancer immunotherapy approaches. Finally, GM-CSF and to a lesser extent IL-3 play a critical role in experimental models of trained immunity by acting not only on bone marrow precursors but also directly on mature myeloid cells. Altogether, characterizing GM-CSF and IL-3 as central mediators of innate immune activation is poised to open new therapeutic avenues for several immune-mediated disorders and define their potential in the context of immunotherapies.
32039403 Liver fibrosis and CD206(+) macrophage accumulation are suppressed by anti-GM-CSF therapy. 2020 Feb BACKGROUND & AIMS: Chronic liver inflammation leads to fibrosis and cirrhosis and is associated with an accumulation of intrahepatic TNFα-secreting CD206(+) macrophages, which may participate in maintaining chronic liver disease in a GM-CSF-dependent manner. We aimed to elucidate the exact role of GM-CSF in the development and progression of chronic liver disease. METHODS: Liver immunohistochemistry and serum quantification were performed in patients with viral and non-viral-related liver disease to compare CD206(+) monocyte/macrophages, fibrosis and GM-CSF. This was followed by functional validations in vitro and in vivo in humanised mice. RESULTS: Using multiplex immunofluorescence and histo-cytometry, we show that highly fibrotic livers had a greater density of CD206(+) macrophages that produced more TNFα and GM-CSF in the non-tumour liver regions of patients with hepatocellular carcinoma (n = 47), independent of aetiology. In addition, the absolute number of CD206(+) macrophages strongly correlated with the absolute number of GM-CSF-producing macrophages. In non-HCC chronic HCV(+) patients (n = 40), circulating GM-CSF levels were also increased in proportion to the degree of liver fibrosis and serum viral titres. We then demonstrated in vitro that monocytes converted to TNFα-producing CD206(+) macrophage-like cells in response to bacterial products (lipopolysaccharide) in a GM-CSF-dependent manner, confirming the in vivo normalisation of serum GM-CSF concentration following oral antibiotic treatment observed in HBV-infected humanised mice. Finally, anti-GM-CSF neutralising antibody treatment reduced intrahepatic CD206(+) macrophage accumulation and abolished liver fibrosis in HBV-infected humanised mice. CONCLUSIONS: While the direct involvement of CD206(+) macrophages in liver fibrosis remains to be demonstrated, these findings show that GM-CSF may play a central role in liver fibrosis and could guide the development of anti-GM-CSF antibody-based therapy for the management of patients with chronic liver disease. LAY SUMMARY: Liver fibrosis is a major driver of liver disease progression. Herein, we have shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the development of liver fibrosis. Our findings support the use of anti-GM-CSF neutralising antibodies for the management of patients with chronic liver disease resulting from both viral and non-viral causes.
31610948 Comparison of low-profile locking plate fixation versus antegrade intramedullary nailing f 2019 Dec BACKGROUND: The purpose of this study was to compare the effectiveness of mini-open antegrade intramedullary nailing (AIN) and open reduction and internal fixation (ORIF) using the low-profile locking plate for angulated metacarpal shaft fractures, through prospective comparative trial. METHODS: Group 1 (mini-open AIN; 40 patients) and the other consecutive patients in group 2 (locking plate; 35 patients) who met our inclusion/exclusion criteria were investigated between January 2010 and December 2016. We compared radiological findings (e.g., union and residual angulation or shortening); clinical conditions (e.g., pain, measured on a visual analog scale (VAS), and Disabilities of the Arm, Shoulder, and Hand (DASH) scores); active range of motion (ROM); and grip strength. RESULTS: Union was achieved in both groups without any major complications. The final angulation measurements were not significantly different (p = 0.402). The final VAS scores were not different (p = 0.868); however, the final DASH score was better in group 1 than in group 2 (p = 0.034). The plates were removed in 14 patients at 9.6 months postoperatively for various reasons. Mean ROM at the time of hardware removal in these 14 patients was significantly lower compared with the final ROM in groups 1 and 2 (non-removal patients). Final grip strengths recovered significantly more in group 1 than in group 2 (p = 0.029). Extension lag was found in four patients in group 2, and the mean amount was 15°; however, it was resolved by tenolysis during hardware removal. CONCLUSIONS: Both mini-open AIN and low-profile plate fixation are excellent options for metacarpal shaft fractures without significant radiological or clinical problems; however, some clinical outcomes evaluated at least 2 years postoperatively, such as DASH scores and grip strength, were better in the AIN group than in the locking plate group. Plate removal was performed under anesthesia in some patients in the plate group for various reasons, and this may have caused the small differences in the final outcomes evaluated 2 years after surgery.
31229523 A novel mPGES-1 inhibitor alleviates inflammatory responses by downregulating PGE(2) in ex 2019 Oct We previously reported the strong inhibitory potency of N-phenyl-N'-(4- benzyloxyphenoxycarbonyl)-4-chlorophenylsulfonyl hydrazide (PBCH) on lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2)) production in macrophages. Herein, we characterized PBCH as a microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor and evaluated its anti-inflammatory effects using in vivo experimental models. PBCH inhibited PGE(2) production in various activated cells in addition to inhibiting the mPGES-1 activity. In the ear edema and paw edema rat models, PBCH significantly reduced ear thickness and paw swelling, respectively. Besides, in adjuvant-induced arthritis (AIA) rat model, PBCH decreased paw swelling, plasma rheumatoid factor (RF), and receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio. Furthermore, while PBCH reduced the plasma prostaglandin E metabolite (PGEM) levels, it did not affect the plasma levels of prostacyclin (PGI(2)) and thromboxane A(2) (TXA(2)). Our data suggest that PBCH downregulates PGE(2) production by interfering with the mPGES-1 activity, thus reducing edema and arthritis in rat models.
31791379 Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high mo 2019 Dec 2 BACKGROUND/PURPOSE: Elevated levels of C-reactive protein (CRP) in systemic sclerosis (SSc) have been linked to early inflammatory stages of the disease. This study has been designed to investigate CRP levels longitudinally in a cohort of SSc patients and to correlate these findings with comorbidities and disease characteristics. METHODS: In this retrospective study, patients with SSc treated at the outpatient clinic of the Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, were analyzed. Only patients with at least three consecutive visits and at least 1 year follow-up were included in this study. CRP serum levels were measured at every visit and categorized as positive if CRP concentrations were ≥ 5 mg/l. Subjects with elevated CRP levels at more than 80% of visits were defined as inflammatory SSc. The longitudinal CRP profiles were correlated with disease characteristics and comorbidities. RESULTS: A total of 1815 consecutive visits of 131 SSc patients were analyzed. Over the observed time span (7.6 (1.0-19.5) years), 18.3% (n = 24) of patients had continuously elevated CRP levels (inflammatory SSc), whereas in 29% (n = 38), CRP levels were always in the normal range. There was no association between disease duration and CRP levels at first visit. Inflammatory SSc was associated with male gender (p = 0.022), anti-Scl-70 antibodies (p = 0.009), diffuse cutaneous SSc (p = 0.036), pulmonary fibrosis (p < 0.001), rheumatoid arthritis (p = 0.007), and cardiac arrhythmia (p = 0.048). Moreover, patients with inflammatory SSc revealed higher modified Rodnan skin scores (p < 0.001); lower forced vital capacity (FVC) (p < 0.001), total lung capacity (p = 0.001), and diffusing capacity (p = 0.008); and faster decline of FVC per year (p = 0.007). Even treatment with cyclophosphamide (CYC) did not decrease CRP levels (p = 0.754). CONCLUSION: Inflammatory SSc is characterized by a more severe phenotype, high morbidity, and a large proportion of male patients. Even treatment with CYC does not alter CRP levels in this subpopulation with a high unmet medical need.
31377093 Opioid Prescriptions for Acute and Chronic Pain Management Among Medicaid Beneficiaries. 2019 Sep INTRODUCTION: Millions of Americans are affected by acute or chronic pain every year. This study investigates opioid prescription patterns for acute and chronic pain management among U.S. Medicaid patients. METHODS: The study used medical and pharmacy claims data obtained from the multistate Truven MarketScan Medicaid Database from 2013 to 2015 for Medicaid patients receiving health care. Medicaid beneficiaries who utilized an outpatient healthcare facility for back pain, neck pain (cervicalgia), joint pain (osteoarthritis and rheumatoid arthritis), orthopedics (simple/closed fractures and muscle strains/sprains), headache (cluster headaches and migraines), dental conditions, or otorhinolaryngologic (otalgia) diagnoses, based on the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, and received an opioid prescription within 14 days of diagnosis were included in this study. RESULTS: There were 5,051,288 patients with 1 of the 7 diagnostic groupings; 18.8% had an opioid prescription filled within 14 days of diagnosis. Orthopedic pain (34.8%) was the primary reason for an opioid prescription, followed by dental conditions (17.3%), back pain (14.0%), and headache (12.9%). Patients receiving an opioid for conditions associated with acute pain management, such as otorhinolaryngologic (OR=1.93, 95% CI=1.85, 2.0), dental (OR=1.50, 95% CI=1.48, 1.53), or orthopedic conditions (OR=1.31, 95% CI=1.29, 1.32), were more likely to receive the prescription from an emergency department provider versus a general practitioner. However, compared with general practitioners, other providers were more likely to prescribe opioids for conditions associated with chronic pain management. CONCLUSIONS: More than half of Medicaid beneficiaries receiving an opioid for pain management do so for orthopedic- and dental-related reasons, with emergency department providers more likely to prescribe opioids. Modifications to the guidelines addressing temporary acute pain management practices with opioids would be likely to benefit emergency department providers the most.
31557376 Toxic effects of triptolide on adrenal steroidogenesis in H295R cells and female rats. 2019 Nov Triptolide (TP), a major active ingredient of Tripterygium wilfordii, exerts potent immunosuppressive effects in the treatment of rheumatoid arthritis but is not widely used in clinical practice due to its multiorgan toxicity, particularly hepatotoxicity, nephrotoxicity, and reproductive toxicity. An LC-MS/MS approach was employed to explore the endocrine-disrupting effects of TP. The endocrine-disrupting effects of various concentrations (0-100 nM) of TP for 48 hour were firstly investigated using an in vitro model (H295R cell line). It was found that TP did not decrease cell viability. The transcriptional levels of steroidogenic enzymes in H295R cells were assessed by quantificational real-time polymerase chain reaction. The possible adrenal and endocrine effects of oral administration of TP (0, 50, and 500 μg/kg) for 28 days on both normal and collagen-induced arthritis (CIA) rats were also explored. The serum and adrenal tissue hormone levels (corticosterone and progesterone) and adrenal histopathology were analyzed, with the results that TP significantly decreased the level of cortisol in H295R cells and the level of plasma corticosterone in both normal and CIA rats. Histological alterations in adrenal cortex were observed at the dose of 500 μg/kg. Exposure to TP for 48 hour had an obvious inhibitory effect on the messenger RNA transcript levels of HSD3B2, CYP21A2, CYP17A1, and CYP11B1, which is essential for the synthesis of corticosteroids. In a word, TP leads to the disorder of corticosteroid synthesis and secretion, and corticosteroid may be a potential biomarker for the treatment of multiorgan toxicity of TP.
31604447 Comparing the burdens of opportunistic infections among patients with systemic rheumatic d 2019 Oct 12 OBJECTIVE: To estimate and compare the burdens of opportunistic infections and herpes zoster in real-world practice among patients with various systemic rheumatic diseases. METHODS: This 13-year cohort study used national health insurance data to compare the incidence rates (IRs) of nine opportunistic infections among patients with five rheumatic diseases. The analyses were stratified according to follow-up duration using Poisson regression, and Cox models were used to compare the risk of first opportunistic infection. RESULTS: During 2000-2013, we identified 76,966 patients who had polymyositis/dermatomyositis (PM/DM, 2270 cases), systemic lupus erythematosus (SLE, 15,961 cases), systemic sclerosis (SSc, 2071 cases), rheumatoid arthritis (RA, 38,355 cases), or primary Sjögren's syndrome (pSS, 18,309 cases). The IR of opportunistic infections was highest for PM/DM cases (61.3/1000 person-years, 95% confidence interval [CI] 56.6-66.2), followed by SLE cases (43.1/1000 person-years, 95% CI 41.7-44.5), SSc cases (31.6/1000 person-years, 95% CI 28.3-35.1), RA cases (25.0/1000 person-years, 95% CI 24.4-25.7), and pSS cases (24.1/1000 person-years, 95% CI 23.1-25.2). Multivariable Cox analysis revealed that, relative to SLE, PM/DM was associated with a significantly higher risk of opportunistic infections (hazard ratio 1.18, 95% CI 1.08-1.29). The risk of opportunistic infections was highest during the first year after the diagnosis of all five rheumatic diseases. CONCLUSIONS: The risk of opportunistic infection was highest for PM/DM, followed by SLE, SSc, RA, and pSS. Careful observation and preventive therapy for opportunistic infections may be warranted in selected PM/DM patients, especially during the first year after the diagnosis.
30871515 Dual actions on gout flare and acute kidney injury along with enhanced renal transporter a 2019 Mar 12 BACKGROUND: Prolonged hyperuricemia is associated with kidney disease or gouty arthritis. Whether Yokuininto, a commercially available Kampo medicine that has been used for osteoarthritis or rheumatoid arthritis, can exhibit anti-hyperuricemic and inflammatory effects remains elusive. In the present study, Yokuininto exerts multiple homeostatic action on serum uric acid (sUA) levels by blocking pro-inflammatory cytokine activities and inducing uricosuric function with anti-renal injury functions. METHODS: The sUA was measured in potassium oxonate (PO)-administered mice. Renal transporter uptake assays were performed using HEK293 cells overexpressing OAT1, OCT2 or OAT3, MDCKII cells overexpressing BCRP, and Xenopus oocytes overexpressing OAT3 or URAT1. Immunoblot and ELISA assays were performed to detect the molecules (OAT3, GLUT9, XO, NGAL, KIM-1 and IL-1α) in various human kidney cell lines. Cell viability analysis was performed to evaluate the cytotoxicity of Yokuininto [Ephedrine + pseudoephedrine 21.94%; Paeoniflorin 35.40% and Liquiritin 16.21% relatively measured by the ratios (HR-MS2 intensity / HR-MS1 intensity)]. RESULTS: Yokuininto (300 mg/kg) significantly reduced sUA by approximately 44% compared to that of PO-induced mice. The OAT3 levels were decreased in PO-induced hyperuricemic condition, whereas the GLUT9 transporter levels were markedly increased. However, PO did not alter the levels of URAT1. Yokuininto significantly inhibited the lipopolysaccharide (LPS)-induced secretion of IL-1α by approximately 63.2% compared to the LPS-treated macrophages. In addition, Yokuininto inhibited nitric oxide synthesis by approximately 33.7 (500 µg/mL) and 64.6% (1000 µg/mL), compared to that of LPS-treated macrophages. Yokuininto markedly increased xanthine oxidase inhibition activity. Furthermore, interleukin-1α (IL-1α), a pro-inflammatory cytokine, elevated neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) activities in LLC-PK1 cells. Expression of renal inflammatory biomarkers, NGAL and KIM-1, was reduced under the Yokuininto treatment by 36.9 and 72.1%, respectively. CONCLUSIONS: Those results suggest that Yokuininto may suppress inflammation and protect against kidney dysfunction in hyperuricemia. The present findings demonstrated that Yokuininto lowered sUA through both increased uric acid excretion and decreased uric acid production. Our results may provide a basis for the protection of prolonged hyperuricemia-associated kidney injury with uric acid-lowering agents such as Yokuininto.
30807792 Prevalence of autoimmune diseases and clinical significance of autoantibody profile: Data 2019 Jul AIM: The objective of this study was to explore the prevalence of various autoimmune diseases (AIDs) in a large cohort of patients and to characterize the autoantibody profile in the patients with and without AIDs to confirm the diagnosis and to refine the Moroccan databases. PATIENTS AND METHOD: Retrospective study was conducted in the Laboratory of autoimmunity National Institute of Hygiene (NIH) of Rabat in Morocco. A total of 3182 consecutive Moroccan patients (2183 females and 999 males) whose sera were tested for 14 autoantibody profile between 2010 and 2016. RESULTS: Only 944 (29.7%) patients were diagnosed with AIDs of those suspected. The prevalence of systemic lupus erythematosus (SLE), intestinal malabsorption (IM) and arthritis polyarthralgia (AP) were the highest (4.2, 4.1 and 4%), subsequently followed by rheumatoid arthritis (RA) (2.8%), cholestatic syndrome (CS) (1.8%), interstitial lung disease (ILD) (1.6%).In females IM, AP and SLE also showed the highest prevalence (5.4%, 5.3% and 4.9% respectively), while of male, SLE showed the highest prevalence (1.9%). The prevalence of ANA was increased in most patients with systemic especially in neuropathy (NP), hemolytic anemia (HA), primary Sjogren's syndrome (pSS), dermatomyositis (DM), thrombocytopenia (Tb), systemic sclerosis (SSc), ANCA-associated vasculitis (AAV), AP, Renal impairment (RI), SLE, and mixed connective tissue disease (MCTD). Anti-dsDNA antibodies were higher in SLE and ENA showed the highest titers in MCTD. Others are relatively specific for certain disease, such as anti β2GP1 for thrombosis syndrome, anti ANCA for primary sclerosing cholangitis (PSC), AAV, ILD and RI, anti CCP2 for RA, ILD and AP. the prevalence of anti AMA was higher in primary biliary cirrhosis (PBC), followed in CS, also, ANA have been identified in up to 25% of patients with primary biliary cirrhosis. The prevalence of anti-SMA was higher in PBC, treated patients for Chronic hepatitis C (HCV), and autoimmune hepatitis (AIH) and anti-PCA was higher in biermer anemia patients with vitamin B12 deficiency (BA/Def vit B12). The prevalence of IgA EMA, IgA tTG and IgA AGA were higher in patients IM and celiac disease (CD). The prevalence of anti thyroperoxidase (TPO) was significantly increased in the autoimmune thyroiditis (AIT). CONCLUSION: Our study shows the diagnostic value of auto antibodies in AIDs. It would be interesting to carry out prospective studies on each pathology separately, in order to fill the classic vagaries of the retrospective study and objectively estimate the prevalence in different AIDs. These data on the prevalence of each autoimmune disease are valuable for the public health system.
32008032 Biologic therapy use and pregnancy outcomes in women with immune-mediated inflammatory rhe 2019 Oct INTRODUCTION: Concerns about the side effects and interactions of biologic drugs with reproduction and pregnancy have been always an issue between experts. The safety of these therapies during conception and/or pregnancy is not fully understood. The aim of this study was to assess the exposure to biologic drugs before and/or during conception/pregnancy and the risk of adverse pregnancy outcomes in women with rheumatic diseases. METHODS: We conducted a cohort study of pregnancies reported in women with immune-mediated rheumatic diseases registered at the Rheumatic Diseases Portuguese Registry (Reuma.pt) and exposed to biologic drugs. Data concerning fetal and maternal outcomes (live birth, spontaneous abortion, neonatal and intrauterine death, intrauterine growth restriction, premature delivery, congenital malformations, neonatal lupus, voluntary or medical interruption of pregnancy, disease flares and need for treatment with other drugs) was extracted. RESULTS: In total, 69 pregnancies from 56 females were analysed, the majority with the diagnosis of spondyloarthritis or rheumatoid arthritis. In almost half of the cases (n=32, 46.4%) the biologic was stopped for pregnancy planning, in 31 cases (44.9%) it was stopped when pregnancy was diagnosed and in 6 pregnancies (8.7%) biologic therapy was maintained, at least until the 2nd trimester. There were 76.8% of live births and 22% of spontaneous abortions. Congenital anomalies were reported in 2 newborns. CONCLUSIONS: In half cases, it was decided to stop biologic therapy in the family planning period. Using biologic disease-modifying anti-rheumatic drugs before and/or during pregnancy doesn't seem to affect the overall maternal and fetal outcomes. Pregnancy planning and treatment options should be discussed and a shared decision should be established between physician and patient.
31866074 [Radiotherapy and immune suppression: A short review]. 2020 Jan The management of patients undergoing immunosuppressive agents is really challenging. Based on precaution principle, it seems mandatory to stop immunosuppressive (or immunomodulating) agents during radiation. Yet, it is impossible in grafted patients. It is possible in patients with autoimmune disease, but in this case, the autoimmune disease might modify patient's radio-sensitivity. We provide a short review about the safety of radiotherapy in grafted/auto-immune patients. The literature is limited with data coming from outdated case-report or case-control studies. It seems that radiotherapy is feasible in grafted patients, but special dose-constraints limitations must probably be considered for the transplant and the other organs at risk. There is very little data about the safety of radiotherapy, when associated with immunomodulating agents. The most studied drug is the methotrexate but only its prescription as a chemotherapy (high doses for a short period of time) was reported. When used as an immunomodulator, it should probably be stopped 4 months before and after radiation. Apart from rheumatoid arthritis, it seems that collagen vascular diseases and especially systemic scleroderma and systemic lupus erythematous feature increased radio-sensitivity with increased severe late toxicities. Transplanted patients and collagen vascular disease patients should be informed that there is very little data about safety of radiation in their case.
31783002 Choline attenuates inflammatory hyperalgesia activating nitric oxide/cGMP/ATP-sensitive po 2020 Jan 15 New findings on neural regulation of immunity are allowing the design of novel pharmacological strategies to control inflammation and nociception. Herein, we report that choline, a 7-nicotinic acetylcholine receptor (α7nAChRs) agonist, prevents carrageenan-induced hyperalgesia without affecting inflammatory parameters (neutrophil migration or cytokine/chemokines production) or inducing sedation or even motor impairment. Choline also attenuates prostaglandin-E(2) (PGE(2))-induced hyperalgesia via α7nAChR activation and this antinociceptive effect was abrogated by administration of LNMMA (a nitric oxide synthase inhibitor), ODQ (an inhibitor of soluble guanylate cyclase; cGMP), andglibenclamide(an inhibitor of ATP-sensitive potassium channels). Furthermore, choline attenuates long-lasting Complete Freund's Adjuvant and incision-induced hyperalgesia suggesting its therapeutic potential to treat pain in rheumatoid arthritis or post-operative recovery, respectively. Our results suggest that choline modulates inflammatory hyperalgesia by activating the nitric oxide/cGMP/ATP-sensitive potassium channels without interfering in inflammatory events, and could be used in persistent pain conditions.
31617124 Therapeutic potential of aryl hydrocarbon receptor in autoimmunity. 2020 Feb Aryl hydrocarbon receptor (AhR), a type of transcriptional factor, is widely expressed in immune cells. The activation of AhR signaling pathway depends on its ligands, which exist in environment and can also be produced by metabolism. Normal expressions of AhR and AhR-mediated signaling may be essential for immune responses, and effects of AhR signaling on the development and function of innate and adaptive immune cells have also been revealed in previous studies. Recent studies also indicate that aberrant AhR signaling may be related to autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), autoimmune uveitis (AU), autoimmune diabetes, Behcet's disease (BD) and myasthenia gravis (MG). Moreover, administration of AhR ligands or drugs has been proven effective for improving pathological outcomes in some autoimmune diseases or models. In this review, we summarize the effects of AhR on several innate and adaptive immune cells associated with autoimmunity, and the mechanism on how AhR participates in autoimmune diseases. In addition, we also discuss therapeutic potential and application prospect of AhR in autoimmune diseases, so as to provide valuable information for exploring novel and effective approaches to autoimmune disease treatments.