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Systemic lupus erythematosus (SLE) is known as an autoimmune disorder that is characterized by the breakdown of self‐tolerance, resulting in disease onset and progression. Macrophages have been implicated as a factor in the development of SLE through faulty phagocytosis of dead cells or an imbalanced M1/M2 ratio. The study aimed to investigate the immunomodulatory effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on M1 and M2 macrophages in new case lupus patients. For this purpose, blood monocytes were collected from lupus patients and healthy people and were cultured for 5 days to produce macrophages. For 48 h, the macrophages were then cocultured with either probiotics or lipopolysaccharides (LPS). Flow cytometry and real‐time polymerase chain reaction were then used to analyze the expression of cluster of differentiation (CD) 14, CD80, and human leukocyte antigen – DR (HLADR) markers, as well as cytokine expression (interleukin [IL]1‐β, IL‐12, tumor necrosis factor α [TNF‐α], IL‐10, and transforming growth factor beta [TGF‐β]). The results indicated three distinct macrophage populations, M0, M1, and M2. In both control and patient‐derived macrophage‐derived monocytes (MDMs), the probiotic groups showed a decrease in CD14, CD80, and HLADR expression compared to the LPS group. This decrease was particularly evident in M0 and M2 macrophages from lupus patients and M1 macrophages from healthy subjects. In addition, the probiotic groups showed increased levels of IL‐10 and TGF‐β and decreased levels of IL‐12, IL1‐β, and TNF‐α in MDMs from both healthy and lupus subjects compared to the LPS groups. Although there was a higher expression of pro‐inflammatory cytokines in lupus patients, there was a higher expression of anti‐inflammatory cytokines in healthy subjects. In general, L. delbrueckii and L. rhamnosus could induce anti‐inflammatory effects on MDMs from both healthy and lupus subjects. Significance statement: Macrophages have been implicated as a factor in the development of systemic lupus erythematosus through faulty phagocytosis of dead cells or an imbalanced M1/M2 ratio. The study aimed to investigate the immunomodulatory effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on M1 and M2 macrophages in new case lupus patients. L. delbrueckii and L. rhamnosus could induce anti‐inflammatory effects on macrophage‐derived monocytes (MDMs) from both healthy and lupus subjects. In both control and patient‐derived MDMs, the probiotic groups showed a decrease in cluster of differentiation (CD) 14, CD80, and Human Leukocyte Antigen – DR expression compared to the lipopolysaccharides (LPS) group. Also observed the increased levels of interleukin (IL)‐10 and transforming growth factor beta and decreased levels of IL‐12, IL1‐β, and tumor necrosis factor α in MDMs from both healthy and lupus subjects compared to the LPS groups. [ABSTRACT FROM AUTHOR]

Objective: Nowadays, the use of telemedicine diagnosis and treatment of various diseases has been considered by physicians, especially in such diseases as rheumatoid arthritis (RA), where patients have more weakness and inability to move. This systematic review aimed to evaluate the extent of measurable and nonmeasurable factors in patients with RA and their satisfaction with this method of care. Methods: The articles published by March 3, 2022, were searched in four databases, including Web of Sciences, Medline, PubMed, and Scopus. This research was conducted using the seven steps of the Cochrane Handbook as a guide. The searched keywords included telemedicine, tele‐rheumatoid, rheumatoid arthritis, and immune diseases. Results: A total of 18 articles were included in the present study. In most of these studies, physicians and patients were satisfied with this approach. Nonetheless, there was a dearth of studies on the measurement of evaluable and nonevaluable factors. Conclusion: Studies on the benefits of telemedicine for rheumatology are still limited. The effectiveness of this new healthcare approach in diagnosing and evaluating disease activity is still unclear. Some studies demonstrated patient and physician satisfaction with this treatment. In some cases, there is a tendency to show a high risk of bias. In addition, it is unclear to what extent the use of rheumatology traps affects the establishment of medical relationships. It is recommended that more clinical trials be conducted to examine this relationship. [ABSTRACT FROM AUTHOR]

Background & Objective: Incomprehensive studies have examined the therapeutic and side effects of curcumin on the treatment of debilitating diseases, such as Rheumatoid Arthritis (RA). This study aimed to explore the antiinflammatory effects of curcumin on RA. Materials & Methods: This double-blind clinical trial was carried out on 64 RA patients with an erythrocyte sedimentation rate (ESR)-Disease Activity Score (DAS)- 28>2.6. The patients were then randomly divided into two groups of intervention and control. In addition to the routine treatment, the intervention group was treated with 80-mg/day capsules of curcumin (nano-micelles). Further, the patients were followed up for three months, and clinical-laboratory examinations were recorded in this study. Results: There was no significant difference between the intervention and control groups regarding the trends of the disease activity indicators, including DAS-28, disability index, physician assessment, and the number of tender joints (P>0.05). Further, a significant difference was found between the two groups in terms of pain score changes and the number of swollen joints. Additionally, the curcumin-treated subjects obtained lower mean pain and fewer swollen joints, compared to those in the control group (P<0.05). Conclusion: The present study revealed that curcumin had no significant therapeutic effects on reducing the activity of RA; however, no significant side effects were observed on the patients, and it also showed its analgesic effect well. [ABSTRACT FROM AUTHOR]

Background & Objective: Systemic Lupus Erythematosus (SLE) is a multisystem autoimmune disorder that its symptoms could affect all aspects of a patient’s quality of life (QoL).This study aimed to assess the quality of life of SLE patients and compare them with those of healthy individuals. It also attempted to compare the QoL of SLE patients suffering from minor and major organ involvement to that of healthy individuals. Materials & Methods: This cross-sectional study was conducted at the Rheumatic Diseases Research Center, Mashhad, Iran, from 2018 to 2019. A total of 280 participants were selected and divided into two groups of patients with SLE (n=139, one of whom was excluded from the case group due to the lack of information.) and healthy controls (n=140). After obtaining the demographic characteristics of the general health, the groups were compared using the 36-Item Short Form Survey (SF36) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire. Results: The mean QoL score was significantly lower in SLE patients, compared to the healthy controls (P<0.001). The total score of QoL was also lower in patients with lung involvement, compared to the healthy controls (P<0.05). Moreover, according to the WHOQOL-BREF, environmental health was lower in patients with lung and skin involvement, compared to the healthy controls (P=0.01). According to the results obtained from the SF-36 questionnaire, the total QoL status was lower in patients with both minor and major organ involvement, compared to the healthy controls (P<0.05). There was also a significant difference between patients with joint involvement and the healthy controls regarding QoL (P=0.02). Conclusion: According to the obtained results, SLE can negatively alter QoL. The severity and activity of the disease in some major organs, including the lung and joints, were associated with reduced QoL. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoid receptor a (GRa) gene is a transcription factor with clinically significant immune-modulating properties in various autoimmune diseases. However, the expression pattern of the GRa gene and associations with clinical features in patients with systemic lupus erythematosus (SLE) is controversial. This study aimed to assess the correlation between the GRa expression and different clinical and laboratory-related parameters in SLE patients. Methods: A total of 45 women with newly diagnosed SLE and 31 gender and agematched healthy controls were enrolled in this cross-sectional study. The real-time quantitative PCR (qRT-PCT) method evaluated the differences in GRa expression in peripheral blood mononuclear cells from cases and controls. The correlation between the GRa gene expression levels, clinicolaboratory features, and potential prognostic application was also analyzed. Results: Compared to the healthy individuals, the GRa gene expression in newly diagnosed SLE patients who did not receive any treatment was numerically reduced, but this reduction did not achieve statistical significance (P=0.87). No significant correlation was also found with the activity and severity of SLE according to SLEDAI2K (P=0.41). The GRa gene expression showed a negative correlation with CRP (P=0.034) and a positive correlation with lupus anticoagulant (P=0.039) levels in SLE. The receiver operating characteristic (ROC) curve analysis indicated that the GRa expression level might be a predictor biomarker for low CRP and positive lupus anticoagulant in SLE, respectively. Conclusion: This study proposed that expression of the GRa in newly diagnosed lupus patients has no statistically significant difference with healthy age and sex-matched controls. Besides, its expression does not correlate with lupus disease activity according to SLEDAI2k. However, further studies in this area are required. [ABSTRACT FROM AUTHOR]

Background: Given the catastrophic results of antiphospholipid syndrome (APS) left untreated, the possible role of non-criteria antiphospholipid (aPL) in the diagnosis of seronegative (SN)-APS patients, and its impact on the timely treatment of people with SNAPS, the present review aimed to gather the available literature up to 2022 focusing on the role of non-criteria aPL in the diagnosis of SN cases suspected of APS using non-criteria aPL. Methods: All published papers focusing mainly on the diagnosis of the SN-APS patients by non-criteria aPL were searched in four databases of PubMed, Scopus, Medline, and Web of Sciences, followed by manual search up to 20 February 2022 using such keywords as "Antiphospholipid Syndrome", "Seronegative", and "Non-Criteria". Finally, 15 studies were selected after the detailed evaluation of the full-text versions. Results: Based on the obtained results of our study, 24% to 81.9% of the SN-APS cases were positive for at least one isotype of non-criteria aPL. Thrombophilia events were more frequent in the APS population, compared to SN-APS; however, obstetric manifestations were more frequent in the SN-APS population, compared to seropositive-APS. Antivimentin/cardiolipin and antiphosphatidylserine/prothrombin IgG/IgM were introduced as the best non-criteria aPL to detect seronegative cases that were correlated with clinical manifestations. Conclusion: It seems that a combination of testing for non-criteria aPL should be performed for cases suspected of APS with negative criteria markers. [ABSTRACT FROM AUTHOR]

The breakdown of self-tolerance of the immune response can lead to autoimmune conditions in which chronic inflammation induces tissue damage. Systemic lupus erythematosus (SLE) is a debilitating multisystemic autoimmune disorder with a high prevalence in women of childbearing age; however, SLE incidence, prevalence, and severity are strongly influenced by ethnicity. Although the mystery of autoimmune diseases remains unsolved, disturbance in the proportion and function of B cell subsets has a major role in SLE's pathogenesis. Additionally, colocalizing hyperactive T helper cell subgroups within inflammatory niches are indispensable. Despite significant advances in standard treatments, nonspecific immunosuppression, the risk of serious infections, and resistance to conventional therapies in some cases have raised the urgent need for new treatment strategies. Without the need to suppress the immune system, mesenchymal stem cells (MSCs), as "smart" immune modulators, are able to control cellular and humoral auto-aggression responses by participating in precursor cell development. In lupus, due to autologous MSCs disorder, the ability of allogenic engrafted MSCs in tissue regeneration and resetting immune homeostasis with the provision of a new immunocyte repertoire has been considered simultaneously. In Brief The bone marrow mesenchymal stem cells (BM-MSCs) lineage plays a critical role in maintaining the hematopoietic stem-cell microstructure and modulating immunocytes. The impairment of BM-MSCs and their niche partially contribute to the pathogenesis of SLE-like diseases. Allogenic MSC transplantation can reconstruct BM microstructure, possibly contributing to the recovery of immunocyte phenotype restoration of immune homeostasis. In terms of future prospects of MSCs, artificially gained by ex vivo isolation and culture adaptation, the wide variety of potential mediators and mechanisms might be linked to the promotion of the immunomodulatory function of MSCs. [ABSTRACT FROM AUTHOR]

Introduction: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disorder in children. Although methotrexate (MTX) is the first line disease-modifying antirheumatic drug for JIA, many patients do not respond well or cannot tolerate MTX. The aim of this study was to compare the effect of combination therapy of MTX and leflunomide (LFN) with MTX in patients who do not respond to MTX. Material and methods: Eighteen patients (2–20 years old) with polyarticular, oligoarticular or extended oligoarticular subtypes of JIA who did not respond to conventional JIA therapy participated in this double-blind, placebo-controlled, randomized trial. The intervention group received LFN and MTX for 3 months while the control group received oral placebo and MTX at a similar dose to the intervention group. Response to treatment was assessed every 4 weeks using the American College of Rheumatology Pediatric criteria (ACRPed) scale. Results: Clinical criteria, including number of active joints and restricted joints, physician and patient global assessment, Childhood Health Assessment Questionnaire (CHAQ38) score, and serum erythrocyte sedimentation ratelevel, did not differ significantly between groups at baseline and at the end of the 4th and 8th weeks of treatment. Only the CHAQ38 score was significantly higher in the intervention group at the end of the 12th week of treatment. Analysis of the effect of treatment on study parameters revealed that only the global patient assessment score differed significantly between groups (p = 0.003). Conclusions: The results of this study showed that combining LFN with MTX does not improve clinical outcomes of JIA and may increase side effects in patients who do not respond to MTX. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a progressive multifactorial inflammatory disorder. According to numerous evidence, pro-inflammatory markers such as TNF-a, IL-6, IL-22, MYD88 and TLR2 play a substantial role in the pathogenesis and persistence of this disease. B-D-Mannuronic acid (M2000) is a new immunosuppressive drug whose therapeutic effects have been approved in several clinical trials and the results of the phase III clinical trial of this drug in RA patients were potent and efficient. Therefore, the present investigation was designed to evaluate its anti-inflammatory effects on the expression of mentioned factors in RA patients. Material and methods: This research was carried out on 12 healthy individuals and 12 patients with RA and M2000 was administered to the patients orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected from the patients before and after treatment with M2000 to investigate the gene expression levels of TNF-a, IL-6, IL-22, MYD88 and TLR2 molecules in them using Real-time PCR. Results: This study data represented a higher gene expression in all target molecules in the RA patients in comparison to the healthy individuals. Furthermore, the outcomes showed that after 12 weeks of therapy with M2000, the gene expression levels of inflammatory factors TNF-a, IL-6, IL-22, MYD88 and TLR2 decreased significantly in treated patients compared to before therapy. The gene expression results were following the clinical and paraclinical assessments. Conclusion: In conclusion, M2000 as a newly approved anti-inflammatory and immunosuppressive drug, can be proposed as a therapeutic agent in RA patients. [ABSTRACT FROM AUTHOR]

Lupus is known as a systemic immune-mediated disorder. Like other diseases in this category, its cause and definitive treatment remain unknown. Gold standard therapies, which mainly include immunosuppressive agents, have been able to have therapeutic effects on patients. However, a significant percentage of cases still do not respond to this kind of treatment, resulting in death from complications. Recently, a new source of non-hematopoietic cells, mesenchymal stem/stromal cells (MSCs), with the potency to re-establishment immune homeostasis and tissue regeneration, has been wildly used in both primary and clinical research. One of the remarkable features of MSCs is their anti-inflammatory and immunosuppressive properties and stimulating tissue differentiation programs. Under the influence of background signals, MSCs migrate to inflammatory bioactive substances and then regulate overactive immune responses to restore immune tolerance. MSCs have shown a two-way interaction with most immunocytes, which plays a significant role in resolving sterile inflammation. Restricting the entry of inflamed cells into the site of inflammation and re-educated infiltrated cells to achieve a tolerant phenotype have been reported as mechanisms of MSCs in tissue repair. Stimulation of the endogenous and tissue-dwelling stem cells in addition to releasing immunomodulatory agents, suggests MSCs transplantation as a potential modality in the treatment of future immune-mediated disorders. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematous (SLE) and rheumatoid arthritis (RA) are autoimmune diseases in which the antigen-antibody system plays an important role. As blood group and Rh are determined by the presence or absence of antigens on the surface of red blood cells (RBCs), we aimed to determine the distribution of ABO and Rh blood groups in SLE and RA patients and its association with disease manifestations. Methods: This short communication is based on a study that was conducted on 434 SLE and 828 RA patients. We evaluated the distribution of ABO and Rh blood groups in RA and SLE patients. Results: This study projected that in lupus patients, Coombs-positive autoimmune hemolytic anemia and arthritis were more common among the B blood type and Rh-positive group, respectively. Furthermore, there was no relation between ABO and Rh blood group and rheumatoid factor (RF) and anti-Cyclic Citrullinated Peptide (anti-CCP) seropositivity. Moreover, there was no difference in distribution of blood groups in RA and SLE patients. Conclusion: The higher frequency of blood group B in hemolytic anemia, and positive Rh in arthritis in lupus patients, develop the hypothesis of probable role of ABO blood group antigen in some manifestations of lupus. [ABSTRACT FROM AUTHOR]

Objective: Recently, saffron (Crocus sativus L. from the Iridaceae family) has been characterized by its antioxidant, anti-inflammatory and analgesic effects. This study aimed to evaluate the effect of saffron on disease activity in patients with rheumatoid arthritis (RA). Materials and Methods: This is a double-blind, placebocontrolled, randomized clinical trial (RCT) performed on 55 newlydiagnosed RA patients without previous treatment, who were randomly divided into intervention (included 28 cases) and control groups (consisted of 27 individuals). Standard therapy including prednisolone, oral methotrexate, folic acid, vitamin D, calcium, and alendronate, was administered similarly in both groups. Patients received a 100 mg saffron pill/day (pure saffron powder) or placebo besides the standard protocol. The placebo had the same shape as the saffron pills. Follow up of DAS28ESR disease activity score was done on the 30th, 45th and 90th day of the study. Results: There was no difference between the intervention and control groups regarding to the DAS28ESR at the end of the study. However, a significant decrease in DAS28-ESR was observed in each group compared to the first visit (p=0.001). The results also showed no significant difference in the incidence of side effects in both groups. Conclusion: In summary, patients who received pure saffron pills (100 mg/day) in addition to standard therapy did not have a significant difference in improvement of disease activity from the patients on standard therapy. [ABSTRACT FROM AUTHOR]

To assess the outcome of planned pregnancies in patients with systemic lupus erythematosus (SLE). Patients and methods: The study was conducted on 32 patients. The medical management included pre-pregnancy planning at the quiescent phase of the disease and after at least six months of clinical remission. The patients had a monthly visit during pregnancy and three months post-delivery. Disease flare was characterized by the recurrence of symptoms and signs in different organs, as well as the need for an increase in medication dose. Results: There were 36 planned pregnancies in 32 patients, of which 15 and 17 cases were primiparous and multiparous, respectively. The SLE flares were observed in 36.1% of the cases, 8.3% of which developed postpartum; moreover, they were moderate in severity and mostly involved the kidneys and joints. Pregnancy outcomes included18 (50%) cases ended in term labor; 13 (36.1%) pregnancies had preterm labor, and 5 (13.8%) pregnancies terminated with abortions. Furthermore, obstetric complications included 2(6.5%) patients with premature rupture of membranes, 5(15.6%) fetuses with intrauterine growth retardation, and 2(6.4%) mothers with preeclampsia. 10(27.7%) pregnancies occurred in patients with lupus nephritis. Cesarean section was performed on 24(77.4%) patients, and low birth weight was observed in 7(21.8%) infants. None of the infants had neonatal lupus, congenital deformities or infection. Conclusion: Pre-pregnancy planning in patients with SLE can considerably improve pregnancy outcomes. Neonatal lupus, congenital anomalies or infection were not present. SLE patients intending to become pregnant should be provided with close medical supervision for a safe maternal and fetal outcome. [ABSTRACT FROM AUTHOR]

BACKGROUND: Interleukin-18 (IL-18) is a pro-inflammatory and pro-atherogenic factor, and its blood level has shown a direct correlation with atherosclerosis. We aimed to evaluate the serum IL-18 level in patients with systemic lupus erythematosus (SLE) and its relationship with the intima-media thickness (IMT) of the carotid artery in these patients, as an indicator of atherosclerosis. METHODS: In this cross-sectional study, 60 patients as the patient group and 30 healthy volunteers as the control group [matched sex, age, and body mass index (BMI)] were selected, and their disease status and general data were gathered using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) form. A blood sample was also obtained from all participants to determine the serum level of IL-18 and other metrics, including high-sensitivity C-reactive protein (hs-CRP), cholesterol, triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), anti-double stranded deoxyribonucleic acid (anti-dsDNA), complement 3 (C3), and C4. The IMT of the carotid artery was calculated in both groups. We also evaluated the clinical cardiovascular manifestations. RESULTS: The serum IL-18 levels in patients were significantly higher than in the control group (P ˂ 0.005). It had no significant correlation with disease activity (P = 0.10). The patients with SLE with high IL-18 serum levels (> 280 pg/ml) had higher SLEDAI-2K (P = 0.02) than the patients with a low level (< 280), where 280 was the median of the IL-18 levels. The serum IL- 18 level had no significant correlation with the carotid artery IMT. CONCLUSION: A high level of IL-18 reflects the disease activity, but it was not significantly correlated with subclinical atherosclerosis, denoted by the carotid artery IMT. [ABSTRACT FROM AUTHOR]

Early cardiovascular disease is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The study was designed to assess the relationship between the serum levels of adipokines and atherosclerotic risk factors in SLE patients. 56 patients and 31 control were included. Serum levels of leptin, adiponectin, traditional and new risk factors for atherosclerosis including plasma glucose levels, lipid profile, high-sensitivity C-reactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) and homocysteine were measured. The intima-media thickness (IMT) of the carotid was measured by ultrasonography. The SLE disease activity index (SLEDAI-2k) was assessed. The patients mean age was 30.8 ± 9.9 years, disease duration was 55.7 ± 59.3 months and were 54 (91.5%) females and 5 (8.5%) males. Serum adiponectin levels were significantly lower in patients (3.58 ± 0.4 ng/ml) compared to control (3.9 ± 0.26 ng/ml) (p < 0.001) while leptin levels were comparable. Serum adiponectin levels correlated with triglyceride (r = 0.3, p = 0.003) and high-density lipoprotein (HDL) (r = 0.2, p = 0.04). Serum leptin significantly correlated with the BMI and total cholesterol (r = 0.43, p = 0.002 and r = 0.3, p = 0.04 respectively) as well as with the anti-double stranded deoxyribonucleic acid (anti-dsDNA) (r = 0.28, p = 0.04). There was lack of a meaningful relationship between serum adiponectin and leptin levels and disease duration or risk factors such as hsCRP, VCAM, homocysteine and IMT as well as with the SLEDAI-2k or complement. Serum adiponectin levels inversely correlate with HDL. A significant correlation of leptin with BMI and total cholesterol was found in SLE. None of the two adipokines were associated with atherosclerosis as assessed with the carotid IMT or with the disease activity. [ABSTRACT FROM AUTHOR]

Context: miR-146a, its targets (IRAK1, TRAF6) and NF-κB transcription factor play a fundamental role in rheumatoid arthritis (RA). Positive effects of drug β-d-mannuronic acid (M2000) were proven on their expression in the HEK-Blue hTLR2 cell line, and results of its phase III clinical trial on RA patients were encouraging. Objective: This research aimed to investigate the effects of M2000 on expression of these genes and serum levels of IL-6 and TNF-α as pro-inflammatory cytokines in RA patients. Material and methods: In this study (Trial Registration Number: IRCT2017100213739N10), 12 RA patients (according to the American College of Rheumatology criteria) and 12 healthy subjects (as control group) were selected. The gene expression of miR-146a, IRAK1, TRAF6, and NF-κB were measured at the baseline and after 12 weeks M2000 therapy, using quantitative real-time PCR method. Moreover, the serum levels of IL-6 and TNF-α were evaluated at the similar times by ELISA method. Results: Our findings showed that the gene expression of miR-146a, IRAK1, TRAF6, and NF-κB significantly decreased after 12 weeks M2000 therapy in RA patients (0.81-, 0.68-, 0.79-, 0.82-fold, with p <.05, p <.01, p <.01, p <.05, respectively). Furthermore, the serum levels of IL-6 and TNF-α significantly reduced in these patients after 12 weeks M2000 therapy (both with p <.05). Conclusions: The present research results determined the part of molecular mechanisms of drug M2000 in RA treatment, based on the expression and function modification of miR-146a, IRAK1, TRAF6, NF-κB, IL-6 and TNF-α. [ABSTRACT FROM AUTHOR]

The positive impacts of β‐d‐mannuronic acid (M2000) on the gene expression of miR‐155, its target molecules (SOCS1 and SHIP1), and NF‐κB transcription factor were demonstrated in a study using the HEK293‐TLR2 cell line. This new drug has been approved as a safe and effective medication by a randomized, multinational, phase III clinical trial on RA patients. The present study aimed to evaluate the oral administration effect of M2000 on the expression levels of the mentioned genes in RA patients. This research was conducted on 12 RA patients and 12 healthy individuals. After extraction of total RNA from PBMCs of patients and synthesis of cDNA, the expression levels of miR‐155, SOCS1, SHIP1, and NF‐κB genes were measured through quantitative Real‐time PCR at baseline and after 12 weeks of M2000 therapy. Our findings showed that the miR‐155 gene expression level significantly decreased in the M2000‐treated patients compared with the baseline (0.76‐fold, with p <.05). The expression levels of SOCS1 and SHIP1 genes significantly increased in the patients treated with M2000 compared with the before treatment (1.46‐, 1.54‐fold, with p <.01, p <.05, respectively). In addition, it was found that the gene expression level of the NF‐κB transcription factor significantly reduced in M2000‐treated patients compared with the baseline (0.81‐fold, with p <.05). This study showed that the oral administration of M2000 was able to reduce the expression of the miR‐155, increase the expression of SOCS1 and SHIP1, and decrease the NF‐κB gene expression (Trial Registration Number: IRCT2017100213739N10). [ABSTRACT FROM AUTHOR]

Objectives: This study aims to review the studies evaluating the therapeutic effects of rivaroxaban versus those of warfarin in patients with antiphospholipid syndrome (APS). Materials and methods: The study included randomized clinical trials, comparative studies, cross-sectional investigations, and case series that focused on the effects of warfarin and rivaroxaban and compared the effects of these anticoagulants in patients with APS. The relevant articles published until 2018 were searched in several databases, including PubMed, Scopus, ScienceDirect, Google Scholar, Embase, and Web of Science. Results: The findings of the reviewed studies showed that rivaroxaban can be used as an effective and safe alternative to warfarin in APS patients. However, the effectiveness of rivaroxaban in the prevention of thrombosis in high-risk APS patients is suspected. Conclusion: Given the high risk of using rivaroxaban in thrombotic APS patients with labile international normalized ratio (INR) or poor adherence to INR monitoring, it is not suggested to use this agent for these patients. [ABSTRACT FROM AUTHOR]

Nowadays, the development of factor VIII and IX inhibitors in patients with hemophilia is considered as the most challenging in the treatment of hemophilia. Immune tolerance induction (ITI) therapy is an approach for eradication of inhibitors. Some ITI protocols are routinely in use for the eradication of inhibitors in patients with hemophilia. Moreover, such a therapeutic regimen may facilitate the tendency to reduced bone density in patients with inhibitor. This study scheduled to investigate whether that predisposing role of ITI protocols with an immunosuppressive agent has considered or not. By a literature review, published ITI protocols in hemophilia with inhibitors were evaluated. Among them, 51 papers found and studied thoroughly. None of them had performed the bone mineral examination in patients with hemophilia and inhibitor under treatment. Since there are 2 coexisting facilitating factors in these protocols, considering the bone mineral density study for patients with inhibitor who are undergoing ITI protocols with an immunosuppressive agent is recommended. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to determine the relationship between the serum hepcidin level and disease activity in patients with rheumatoid arthritis (RA). Methods: This study was conducted on 80 patients with RA (36 cases with anemia of chronic disease [ACD] and 44 patients without ACD). Disease activity was measured by the 28-joint Disease Activity Score based on the erythrocyte sedimentation rate (DAS28-ESR). According to the DAS28-ESR score, 52 and 28 cases were categorized as inactive to moderately active RA (DAS28-ESR=5.1) and highly active RA (DAS28-ESR>5.1), respectively. In addition, the serum hepcidin level was evaluated in all patients to determine its correlation with the DAS28-ESR score. Results: There was no significant difference between the RA with ACD and RA without ACD groups in terms of the median (interquartile range) hepcidin level (1207 [985.2] vs. 923.8 [677.3] ng/mL; P=0.57). Likewise, no significant difference was observed between the active RA and inactive to moderately active RA groups in this regard (1131.8 [991.3] vs. 1090.9 [631.4] ng/mL; P=0.53). Conclusion: Hepcidin has no association with disease activity in RA. Therefore, it is not necessary to measure hepcidin to determine the RA activity. [ABSTRACT FROM AUTHOR]

Objective(s): Juvenile idiopathic arthritis (JIA) is one of the most common chronic rheumatic diseases in children. The complex nature of this immune-mediated disease owes itself to several predisposing genes and environmental factors affecting its pathogenesis. Conducted in Iran, this study was originally intended to investigate every possible association between HLA DRB1 alleles and a susceptibility to JIA. Materials and Methods: In this case-control study, 45 patients with a definite diagnosis of JIA based on International League against Rheumatism (ILAR) criteria were compared against 46 healthy controls. DNA samples taken from both groups were analyzed using PCR-sequence specific primers (PCR-SSP) method. Data analysis including parametric and nonparametric test and multivariate analysis was undertaken using the SPSS 11.5 software. A P-value< 0.05 was regarded as statistically significant. Results: Mean ages in case group and healthy controls were 14.64±6.21 and 13.73±6.39, respectively with no significant difference between the two groups (P=0.515). Sex difference between JIA group and healthy controls was also not significant (P=0.068) .The frequency of HLA-DRB1*01 was found the most frequent HLA-RB1 in our patients (33.3%). No significant statistical correlation between various HLA-DRB1 alleles and clinical subtypes of the disease could be established from the data. HLA-DRB1*11 was shown to raise protection to JIA (P=0.035, OR=2.755, 95% CI=0.963-8.055) in northeastern Iran. In addition, we found that HLA-RB1*09 is nominally associated with an increased risk of JIA (P=0.56, OR=2, 05, 95% CI=0.18-23.63). Conclusion: HLA-DRB1*11 was shown to raise protection to JIA in northeastern Iran. The disparity of findings in other ethnicities prompts further investigations with larger sample sizes. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Sarcoidosis is an autoimmune multiorgan granulomatosis disease with unknown origin. Some environmental factors such as viruses may induce the disease in genetically susceptible individuals. Human T cell lymphotropic virus type 1 (HTLV‐1) can dysregulate the human immune system and the role of this virus in the pathogenesis of autoimmune diseases has been investigated and documented, such as in uveitis. In this study, we have focused on the seroprevalence of HTLV‐1 in sarcoidosis in comparison to the normal population in the northeast of Iran, an endemic area for HTLV‐1. Methods: This cross‐sectional study enrolled 125 patients with established sarcoidosis to evaluate the frequency of HTLV‐1 and compare it with the normal population of Mashhad, Iran. Participants’ blood samples were analyzed for HTLV‐1 antibody by an enzyme‐linked immunosorbent assay kit. Positive results were confirmed by polymerase chain reaction method. Finally, data were analyzed using SPSS 11. Results: Among sarcoidosis patients 106 (84.8%) patients had a history of acute course and 19 (15.2%) had chronic sarcoidosis. Four percent of the patients versus 2.12% of the Mashhad population were HTLV‐1 positive with no statistical difference (P = 0.201). In age‐ and sex‐matched selected controls, 3.6% were HTLV‐1 positive again with no statistical difference by sarcoidosis group (P = 0.52). There was no statistical difference between arthritis, erythema nodusom, uveitis, constitutional symptoms, abnormal chest radiography (parahilar lymphadenopathy) and computed tomography scan findings, respiratory symptoms, sex, the course of the sarcoidosis in HTLV‐1 positive and negative sarcoidosis patients. Conclusion: The frequency of HTLV‐1 in 125 sarcoidosis patients was 4%. In comparison with prevalence of HTLV‐1 in Mashhad, HTLV‐1 seroprevalence did not show any significant difference. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are characterized by the attack of the immune system to normal tissues. Patients with autoimmune diseases usually have the deficiency of dietary factors that may be related to the etiology of these conditions. Given the role of vitamin E as a physiologic stabilizer of lysosomal membranes, its deficiency can initiate the process of autoimmune diseases or accelerate its progress. It is supposed that vitamin E could reduce oxidative stress, which is an important factor in the pathogenesis of autoimmune diseases. The literature review is indicative of a decrease in the serum levels of vitamin E in almost all autoimmune diseases. Furthermore, there is evidence regarding the possible therapeutic value of vitamin E in the management of autoimmune diseases. Owing to the anti-inflammatory and protective effect of vitamin E against free radicals, and also its important effect on cytokines levels, this vitamin may play a powerful role in the prevention and treatment of rheumatoid arthritis, as well as joint inflammation and damage. Moreover, increased vitamin E intake might decrease the incidence and severity of certain autoimmune diseases through the regulation of the immune system. [ABSTRACT FROM AUTHOR]

Objective(s): Systemic lupus erythematosus (SLE) is an autoimmune disease with a wide range of clinical manifestations. Cognitive dysfunction is one of the manifestations that could present prior to the emergence of any other neuropsychiatric involvements in SLE. Cognitive dysfunction is a subtle condition occurring with a high frequency. However, there is no data on the correlation of cognitive dysfunction with central nervous system (CNS) imaging findings, in particular single-photon emission computed tomography scan (SPECT) and functional MRI. We decided to perform a systematic review of brain SPECT and fMRI in SLE patients with cognitive dysfunction. Methods: PubMed, Scopus, and Google Scholar databases were searched until April 2017 with the following keywords: "SLE OR systemic lupus erythematous OR lupus" AND "functional MRI OR functional magnetic resonance imaging OR fMRI OR SPECT or SCAN". A total of 1,767articles were found. Two rheumatologists reviewed the articles and finally 14 articles were selected for the final systematic review. Results: The fMRI and SPECT imaging techniques could provide valuable information regarding the SLE patients with cognitive dysfunction at the early stages of the disease. Conclusion: Brain SPECT scan and fMRI are used as functional imaging tools in SLE. Both of these diagnostic modalities are sensitive in reflecting the subtle brain damages in SLE patients with cognitive dysfunction. Brain fMRI and SPECT scan could be significantly beneficial in the diagnosis and initial management of cognitive dysfunction in SLE. Nevertheless, prospective studies could be useful in confirming the application of these diagnostic modalities in the clinical setting. [ABSTRACT FROM AUTHOR]