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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: Increasing evidence suggests that multipotent mesenchymal stem/stromal cells (MSCs) are a promising intervention strategy in treating autoimmune inflammatory diseases. It should be stated that systemic immunoregulation is increasingly recognized among the beneficial effects of MSCs and probiotics in treating morbid autoimmune disorders such as lupus. This study aimed to determine if immunoregulatory probiotics L. rhamnosus or L. delbrueckii can change the immunomodulatory effects of MSCs in lupus-like disease. Methods: Pristane-induced lupus (PIL) mice model was created via intraperitoneal injection of Pristane and then confirmed. Naïve MSCs (N-MSCs) were coincubated with two Lactobacillus strains, rhamnosus (R-MSCs) or delbrueckii (D-MSCs), and/or a combination of both (DR-MSCs) for 48 h, then administrated intravenously in separate groups. Negative (PBS-treated normal mice) and positive control groups (PBS-treated lupus mice) were also investigated. At the end of the study, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to determine the percentage of Th cell subpopulations in splenocytes and the level of their master cytokines in sera, respectively. Moreover, lupus nephritis was investigated and compared. Analysis of variance (ANOVA) was used for multiple comparisons. Results: Abnormalities in serum levels of anti-dsDNA antibodies, creatinine, and urine proteinuria were significantly suppressed by MSCs transplantation, whereas engrafted MSCs coincubation with both L. strains did a lesser effect on anti-dsDNA antibodies. L. rhamnosus significantly escalated the ability of MSCs to scale down the inflammatory cytokines (IFN-ɣ, IL-17), while L. delbrueckii significantly elevated the capacity of MSCs to scale down the percentage of Th cell subpopulations. However, incubation with both strains induced MSCs with augmented capacity in introducing inflammatory cytokines (IFN-ɣ, IL-17). Strikingly, R-MSCs directly restored the serum level of TGF-β more effectively and showed more significant improvement in disease parameters than N-MSCs. These results suggest that R-MSCs significantly attenuate lupus disease by further skew the immune phenotype of MSCs toward increased immunoregulation. Conclusions: Results demonstrated that Lactobacillus strains showed different capabilities in training/inducing new abilities in MSCs, in such a way that pretreated MSCs with L. rhamnosus might benefit the treatment of lupus-like symptoms, given their desirable properties. [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: 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]

Objectives: To present the clinical characteristics, disease course, management, and outcomes of COVID-19 infection in patients with Behcet's disease (BD). Methods: In this retrospective cohort study, we retrieved BD patients with definite diagnosis of COVID-19 infection. Demographic data, comorbidities, features related both to BD and COVID-19 infection, treatments, and outcomes were collected. Comparisons between patients with or without hospitalization were performed. All statistical analyzes were performed using SPSS version 25. We considered p < 0.05 statistically significant. Results: We identified 61 episodes of COVID-19 infection in 59 BD patients. The prevalence was 0.69%. The median age was 45 years (IQR = 20), and the median disease duration was 162 months (IQR = 195). BD features were similar except for higher rate of arterial involvement and positive pathergy test in infected patients. Thirty-five episodes (62.5%) happened in non-active patients; 39% had a comorbid disease. COVID manifestations were the same as the general population. Flu-like symptoms were the most common (85%), followed by fever (66%), ageusia/anosmia (56%), headache (51%), and pulmonary involvement (48%). There was no change in BD symptoms in 74%. Fifteen patients (25.4%) were hospitalized, and one patient (1.7%) died. Receiving glucocorticoids (p < 0.03) and cytotoxic drugs (p < 0.02) were associated with an increased rate of hospitalization. Conclusion: The incidence of COVID-19 infection in BD patients was not higher than general population in Iran. They showed milder form of disease with lower morbidity and mortality rate. Most were on immunosuppressive drugs, or had a comorbidity apart from BD. No significant effect on BD course was shown. Key Points • The incidence of COVID-19 infection in patients with Behcet's disease is not higher. • They showed milder form of infection with lower morbidity and mortality rate. • No significant effect on Behcet's disease course was shown with COVID19 infection. • BD patients can be managed according to the guidelines used for general population. [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]

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]

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]

Background: The oral administration of drug β-d-mannuronic acid (M2000) showed a potent therapeutic effect in phase I/II study in rheumatoid arthritis (RA) patients. Here, our aim is to assess the efficacy and safety of this new drug in RA patients under a multinational, randomized placebo-controlled phase III clinical trial. Method: Patients (n = 288) with active disease at baseline and inadequate response to conventional drugs were randomly allocated to three groups; (1) receiving mannuronic acid at a dose of two capsules (500 mg) per day orally for 12 weeks, (2) placebo-controlled, and (3) conventional. The primary endpoints were the America College of Rheumatology 20 response (ACR20), 28-joint disease activity score (DAS28) and Modified Health Assessment Questionnaire-Disability Index (M-HAQ-DI). In addition, the participants were followed-up for safety assessment. Results: In this phase III trial, after 12 weeks of treatment, there was a significant reduction in ACR20 between mannuronic-treated patients compared to placebo and conventional groups. Moreover, there was a similar significant improvement for DAS28 following mannuronic therapy. The statistical analysis showed a significant reduction in the swollen and tender joint count in mannuronic-treated patients compared with the placebo group. On the other side, mannuronic acid showed no-to-very low adverse events in comparison to placebo. Conclusion: The results of this multinational, phase III clinical trial provided a potent evidence base for the use of β-d-mannuronic acid as a new highly safe and efficient drug in the treatment of RA. [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: 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]

Several studies have estimated breast cancer risk in patients with systemic lupus erythematosus (SLE) relative to the general population. However, the results have been inconclusive. Therefore, we conducted a meta-analysis to ascertain a more comprehensive conclusion. A systematic literature search of electronic databases including PubMed, Web of Science, Embase, Cochrane Library, and Scopus was conducted to identify eligible studies using multiple search strategies. Based on the degree of heterogeneity, a random-effect model was chosen to calculate the pooled standardized incidence rate (SIR) with 95% confidence interval (CI), to estimate the strength of association between SLE and breast cancer incidence risk. A total of 18 eligible studies including 110,720 patients with SLE were enrolled in this meta-analysis. The combined results showed no significant association between SLE and breast cancer incidence (SIRs = 1.012 (95% CI, 0.797-1.284)). Subgroup analysis by study type, ethnicity, follow-up years, sample size, and SLE diagnostic criteria also showed no altered risk for breast cancer incidence (the summary risk estimate of each subgroup ranged from 0.82 to 1.40 with no statistical significance). This meta-analysis suggests no direct association between SLE and risk of breast cancer incidence. [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]

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]

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]

Immunoglobulin G4-related disease (IgG4-related disease) is a fibroinflammatory disorder defined by elevated serum IgG4 level and plasma cells tissue infiltration accompanied by fibrosis or sclerosis. In this article, we report two patients of IgG4 syndrome: a 60-year-old male with complaints of nasal congestion, rhinitis, anosmia and hearing loss, and a 28-year-old female with bilateral orbital and parotid gland swelling. Histopathological findings and high serum IgG4 level confirmed diagnosis of IgG4-related disease. Both patients were treated successfully with glucocorticoids and methotrexate. Herein, we also review clinical presentations of IgG4-related disease in head and neck, and related diagnostic and therapeutic approach. [ABSTRACT FROM AUTHOR]

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Objective(s): Lupus nephritis (LN) is the main cause of mortality and disability in systemic lupus erythematosus (SLE) patients. Therefore, utilizing a reliable and non-invasive method for serial measurements of renal function seems to be necessary. The aim of this study was to evaluate the role of urinary lipocalin-2 as a biomarker of renal involvement in SLE patients. Materials and Methods: Fifty two lupus patients in this cross sectional study were divided into two groups: patients with and without nephritis. For each group, urinary lipocalin-2, values were measured and reported according to urinary lipocalin-2/creatinine. Urinary lipocalin-2/creatinine sensitivity and specificity for identifying biopsy-proven nephritis were calculated, and a receiver operating characteristic (ROC) curve was constructed. Results: The mean urinary lipocalin-2/creatinine value of patients with biopsy-proven LN was 2.99 ± 4.1 ng/mg, and in non-LN patients was 1.16 ± 1.27 ng/mg. Urinary lipocalin-2/creatinine levels in LN patients were significantly higher than those in non-LN patients (P-Value = 0.03). In LN patients, urinary lipocalin-2/creatinine significantly correlated with proteinuria (r = 0.68; P = 0.0001). Using a cutoff value of 0.896 ng/mg, urinary lipocalin-2/creatinine had a sensitivity of 89.7% and a specificity of 39.1% for identifying SLE patients with biopsy-proven LN. The area under the ROC curve was 0.664 ± 0.076 with a 95% confidence interval of 0.52-0.81 (P=0.04). Analysis of variance showed that urinary lipocalin-2/creatinine is the same in different classes of LN (P-value=0.28). Conclusion: An important clinical conclusion is that measurement of urinary Lipocalin-2 may result in earlier diagnosis of LN. [ABSTRACT FROM AUTHOR]

Objective(s): Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology. Some environmental factors can induce SLE in genetically susceptible individuals; for example, sun exposure and some viral infections may emerge the disease manifestations. Human T lymphotropic virus type 1 (HTLV-I) can dysregulate the human immune system, and the role of this virus in the pathogenesis of autoimmune diseases is under investigation. There are conflicting data about the role of HTLV-I in the pathogenesis of several autoimmune diseases such as SLE. In this study, we have focused on the correlation between HTLV-I infection and SLE in the northeast of Iran, an endemic area for the virus. Materials and Methods: One hundred and thirty women with SLE and 915 healthy controls were screened for HTLV-I by enzyme linked immunosorbent assay (ELISA). Western blot method was used for confirmation of the positive results done by ELISA in the patients and the control group. Results: Two (1.5%) of the patients and 23 (2.5%) of the healthy controls were HTLV-I seropositive. There was not a statistical difference between patients and controls in the number of HTLV-I seropositive samples (P=0.49). Conclusion: This cross-sectional case-control study did not find any association between HTLV-I and SLE. With regard to the previous studies, these controversies may stem from differences in ethnic background. Geographical and environmental factors should also be taken into account. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Several cytokines and apoptotic markers such as IL-18 and soluble Fas (sFas) have been assumed to play a role in the pathogenesis of LN. Previous studies confirmed that serum concentrations of sFas and IL-18 are increased in SLE. However, only a few studies have suggested a possible correlation between IL-18 and sFas. This study was planned to continue our previous study on the correlation between those markers to evaluate this correlation in LN. Thirty-two patients with only LN and 46 patients without any major organ involvement participated in this study. SLEDAI score (except for scores related to nephritis) was the same in these two groups. In both groups, patients with any other major organ involvement were excluded. We found a significant rise in the serum concentrations of sFas (P = 0.03) and IL-18 (P = 0.02) in patients with proteinuria compared to those without it. This study showed that the correlation between sFas and IL-18 in LN (P < 0.001, r p = 0.5) is significantly stronger than it is in mild SLE (P < 0.001, r p = 0.4) with similar nonrenal SLEDAI score (P = 0.032, z = 1.85). Between these two serum markers, sFas is the only predictor of proteinuria. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Several cytokines and apoptotic markers such as IL-18 and soluble Fas (sFas) have been assumed to play a role in the pathogenesis of LN. Previous studies confirmed that serum concentrations of sFas and IL-18 are increased in SLE. However, only a few studies have suggested a possible correlation between IL-18 and sFas. This study was planned to continue our previous study on the correlation between those markers to evaluate this correlation in LN. Thirty-two patients with only LN and 46 patients without any major organ involvement participated in this study. SLEDAI score (except for scores related to nephritis) was the same in these two groups. In both groups, patients with any other major organ involvement were excluded. We found a significant rise in the serum concentrations of sFas (P = 0.03) and IL-18 (P = 0.02) in patients with proteinuria compared to those without it. This study showed that the correlation between sFas and IL-18 in LN (P < 0.001, r p = 0.5) is significantly stronger than it is in mild SLE (P < 0.001, r p = 0.4) with similar nonrenal SLEDAI score (P = 0.032, z = 1.85). Between these two serum markers, sFas is the only predictor of proteinuria. [ABSTRACT FROM AUTHOR]

Pre-eclampsia is a pregnancy-specific syndrome that may be dangerous especially to the fetus. Different cytokines have been found to be elevated in women with pre-eclampsia and may have possible roles in the development of this disorder. Alleles of the interleukin-l-beta (IL-β ) and tumor necrosis factor alpha (TNF-α) genes are associated with pr-eeclampsia in several studies in different populations. The aim of the present study was to investigate the relationship between IL-lβ (C+3954T) and TNF-α (G-308A) gene polymorphisms with preeclampsia in north east of Iran (Khorasan province). This study included 54 diagnosed patients with pre-eclampsia and 50 normal pregnant women as control group. DNA was extracted from peripheral blood and the polymorphisms were determined by PCR-RFLP method. Data was analyzed using chi-square and Fisher's exact tests. There was significant association between TNF-α (G-308A) genotype and pre-eclampsia (p=0.001) but we did not find any significant association between IL-lβ (C+3954T) genotype and pre-eclampsia (p=0.39). The present study might suggest a role for TNF-α in the development of pre-eclampsia; however, IL-lβ (C+3954T) polymorphism could not be considered as a marker of susceptibility to preeclampsia in our population. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is the most common autoimmune arthritis. The impact of chronic inflammation on atherosclerosis and insulin resistance has been observed in several autoimmune diseases. On the other hand, metabolic syndrome (MetS); a cluster of traditional risk factors for atherosclerosis and diabetes seems to be prevalent in RA patients. It is reasonable to think that protective factors against inflammation can protect patients against atherosclerosis and diabetes, too. Vitamin D (Vit D), a novel immunomodulator, is recently considered to play a protective role against cardiovascular diseases, insulin resistance, and obesity. This cross-sectional study was designed to evaluate the impact of serum Vit D on MetS and body mass index (BMI). One hundred twenty RA patients were enrolled. MetS was assessed according to Adult Treatment Panel III criteria. All patients with known confounders influencing Vit D serum levels were excluded. Serum value of 25-hydroxyvitamin D (25(OH)D) was measured using a commercial ELISA kit. Data were analyzed by SPSS software. A logistic regression analysis stated that prednisolone dosage [ p = 0.028, β = 0.177, odds ratio (OR) = 1.194, confidence interval (CI, 1.09-1.32)], age [ p = 0.002, β = 0.146, OR = 1.57, CI (1.05-1.27)] and Vit D serum levels [ p = 0.049, β = −3.766, OR = 0.023, CI (0.001-0.978)] are all significant predictors of MetS occurrence in RA patients. It was shown that 25(OH)D is a protective factor against MetS. It was also shown that there is a negative correlation between BMI and 25(OH)D serum levels ( P = 0.037, r = −0.266). In summary, this study suggested that 25(OH)D plays a protective role against MetS in RA patients. However, this cross-sectional study did not permit a power calculation on the causal relationship between Vit D and metabolic syndrome. On the other hand, Vit D has a negative correlation with BMI in these patients. [ABSTRACT FROM AUTHOR]

Recent researches suggest that imbalance in apoptotic process may lead to susceptibility to systemic lupus erythematosus (SLE). Production of pro-inflammatory cytokines, such as IL-18, has important role in autoimmune process in lupus. There are cumulative data on the pro-apoptotic role of IL-18, in the Fas-mediated apoptosis. Soluble Fas (Apo/1-CD95) is a marker of apoptosis that appears to increase in serum of SLE patients. Previous studies demonstrated increasing serum concentrations of soluble Fas (sFas) and IL-18 in SLE. To assess the correlation between serum concentrations of sFas and IL-18 in SLE patients, 114 SLE patients were selected randomly at the different stages of disease activity according to SLEDAI2K. IL-18 and sFas serum concentrations were compared in patients and fifty randomly selected healthy volunteers. The correlations of IL-18 and sFas serum concentrations with SLEDAI2K and with each other were evaluated in patients. There were a significant difference between serum concentrations of sFas and IL-18 in the case and control groups ( P = 0.001). There was a significant correlation between serum concentrations of sFAS and IL-18 in SLE patients ( P < 0.0001, r = 0.411). The elevations of IL-18 and sFas(Apo/1-CD95) serum concentrations in SLE patients are significantly correlated. [ABSTRACT FROM AUTHOR]

In recent decays, quality of life and life expectancy of individuals with severe haemophilia A and B have been improved by better quality in treatment and more availability of blood coagulation products. Recently, new concerns have emerged in current groups such as auto-antibody inhibitors to coagulation factors and reduced bone density (RBD). RBD in bleeding disorders is becoming an escalating burden worldwide due to an increased in life expectancy and also in the ageing population with bleeding disorders. Here, we review published papers on bone mineral density of individuals with haemophilia A & B, a rare bleeding disorder entitled combined factor V and VIII deficiency and other rare bleeding disorders. It seems in individuals with bleeding disorders preventive measures including early detection, treatment and adequate physical activity, encouragement to be active in sports and finally anti-osteoporotic therapy must be done. [ABSTRACT FROM AUTHOR]

Background: Vitamin D has immunomodulatory function. Polymorphisms of the gene encoding the vitamin D receptor detected by BsmI may be source of diversity in its action. An association between vitamin D receptor gene BsmI polymorphisms and lupus nephritis has been reported. This study was performed to evaluate vitamin D receptor gene BsmI polymorphisms in lupus nephritis. Methods: Twenty nine patients with lupus nephritis enrolled in this study. Vitamin D receptor gene typing was performed based on polymerase chain reaction-restriction fragment length polymorphism. Finding: Vitamin D receptor genotyping of BsmI polymorphisms was 20.6% for BB, 51.7% for Bb, and 27.5% for bb without statistically significant difference (P = 0.090). In 21 patients that renal biopsy was done, the Bb genotype was the most (42.8%). There was not any correlation between renal histology and vitamin D receptor gene BsmI polymorphisms (P = 0.068). Conclusion: There was no relationship between vitamin D receptor gene BsmI polymorphisms and lupus nephritis. [ABSTRACT FROM AUTHOR]

Objective(s) Recent studies on human indicate that the introduction of therapeutic use of tolerogenic dendritic cell (DC) for chronic inflammatory conditions is imminent. For the purpose of defining CGRP potency in tolerogenic DC production, we investigated the phenotype and IL-12 production of DCs generated from the monocytes of rheumatoid arthritis (RA) patients in the presence of the calcitonin gene-related peptide (CGRP), as a multifunctional neuropeptide. Materials and Methods DCs were generated from isolated monocytes from four resistant and two early female RA patients using IL-4, GM-CSF, and CGRP at concentrations of 0, 1, and 100 nM. Then, the phenotype of neuropeptide-treated or untreated DCs was determined using flow cytometry and the IL-12 production was measured by ELISA. Results Our study showed that, on the last day of the culture, at a concentration of 1 nM CGRP, the mean fluorescence intensity (MFI) for CD80 increased (14.13%) and the MFIs for CD83, CD86, and HLA-DR decreased (14.57%, 5.28%, and 6.88% respectively). Moreover, at 100 nM CGRP concentration, the MFI for CD80 increased (11.10%) and the MFIs for CD83, CD86, and HLA-DR decreased (4.27%, 18.60%, and 19.75% respectively). In addition, our results indicated that the mean concentrations of IL-12 produced at 0, 1, and 100 nm CGRP concentrations measured 13.72±2.41, 11.01±1.61, and 7±1.34 pg/ml respectively. Conclusion Decreased CD83, CD86, and HLA-DR expression and reduced IL-12 production by CGRP were found in the RA patients' monocyte-derived DCs. CD83 is a well-defined DC activation marker. HLA-DR and CD86 are appropriate molecules for inducing an immune response. IL-12 promotes cell-mediated immunity. Therefore we suggest that CGRP may be used as an inducer in the production of tolerogenic DCs. [ABSTRACT FROM AUTHOR]

Aim: The reduced bone density in individuals with severe hemophilia A (decreased coagulation factor VIII level) and combined factor V and VIII deficiency have been reported. In the current case-control study we tried to address bone mineral density in individuals with severe hemophilia B (decreased coagulation factor IX). Methods: In our case-control study, we recruited bone density and biochemical indexes in 14 individuals with severe hemophilia B and compared obtained results with 14 age- and sex-matched control group results. Results: Our results showed individuals with severe hemophilia B had reduced bone density in lumbar (–0.34 ± 0.97) and femur (–0.82 ± 1.37) regions, compared to the control group (0.84 ± 0.53 and 1.02 ± 1.04 respectively; P-value = 0.000 and 0.000). Conclusion: The foremost complication of coagulation disorders are various types of excessive bleedings. The current study revealed severe hemophiliac B patients are prone to reduced bone density similar to severe hemophiliac A patients. [ABSTRACT FROM AUTHOR]

Aim: Vitamin K is an essential factor for carboxylation of bone matrix protein. Low vitamin K may be associated with reduced bone mineral density (BMD). The issue of whether long-term sodium warfarin therapy as oral anticoagulant that antagonizes vitamin K, results in decreased bone density, is controversial. Our purpose in this study was to assess the effects of warfarin on BMD. Methods: We performed a case control study survey of bone density in 70 patients with rheumatic valvular heart disease ‘mechanical valve replacement’ on long-term warfarin compared with 103 randomly selected matched controls. Results: There was a marked reduction in BMD (g/cm2) and T-score of lumbar spine between patients and controls ( P = 0.048, 0.005). Duration of warfarin use was the only risk factor of significant importance respectively on spinal T-score ( P < 0.03). Conclusions: Screening of patients on long-term warfarin for reduced bone density should be considered. We strongly suggest the prophylactic use of calcium–vitamin D supplements for these patients. [ABSTRACT FROM AUTHOR]

Individuals with severe haemophilia A may be at risk for reduced bone mineral density because of reduced weight-bearing exercise and hepatitis C infection. For confirming the reduced bone density, in the current cross-sectional study, we tried to address bone mineral density in individuals with severe haemophilia A and surveyed the relation of reduced bone density with hepatitis C viruses. To fulfil these aims, bone density and biochemical indexes in 18 individuals with severe haemophilia A and also in 18 individuals matched for age, sex, weight and height, as the control group, were examined. The obtained results showed that individuals with severe haemophilia A had reduced bone density (1.136 ± 0.118, 0.801 ± 0.238) in lumbar and femur regions, respectively, in comparison with the age- and sex-matched group (1.299 ± 0.237, 1.458 ± 0.505). The major complications of coagulation disorders are various types of excessive bleeding. The current study describes an association between severe haemophilia A and osteopenia, specifically at both the femur and the lumbar spine. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease in which polymorphisms within the human leukocyte antigen (HLA) region have been associated to its etiology. We conducted this study to compare the HLA-DQB1 allelic sequence variation among SLE patients and controls in the northeast of Iran. Genomic DNA of 40 SLE patients and 83 healthy controls were amplified by Polymerase Chain Reaction with Sequence-Specific Primers technique (PCR-SSP). Seven serological subclasses of the HLA DQB1 were detected. Allele distribution comparison showed in the SLE group a significant increase of HLA DQ6 (*0601-*0609) (p=0.006); whereas alleles HLA DQ7 (*0301-*0304) were significantly decreased (p=0.005). Combination of DQ5 (*0501-*0504)-DQ6 (*0601-*0609) was increased in patients. These results suggest that DQ6 is the dominant HLA DQB1 allele probably associated with genetic susceptibility to SLE in the northeast of Iran. The association supports the importance of ethnic background and indicates the importance of various genes that has been observed in different SLE populations. [ABSTRACT FROM AUTHOR]

Aim: Rheumatoid arthritis (RA) is the most common chronic inflammatory erosive joint disease with the worldwide distribution of approximately 0.5–1.0%. Etiology of RA is not exactly known but immunologic and genetic factors play an important role in the pathogenesis of the disease. Genetic factors such as human leukocyte antigens (HLA) are responsible for many autoimmune diseases; therefore we decided to look for a correlation between RA and the presence of HLA-DQβ1 alleles as possible genetic markers. Methods: Genomic DNA from the whole blood samples of 25 patients with RA and 86 normal individuals as control group were extracted by salting out method. The genomic DNA was amplified by polymerase chain reaction-sequence specific primer (PCR-SSP) technique. HLA-typing was done by this method after optimizing the PCR reaction for each allele. In this procedure seven serological subclasses of HLA-DQβ1 can be detected. Results: Comparing the results between the patients and controls show a significant increase in the frequency of HLA-DQ8 (*0302, *0305) alleles in RA patients. The P-values were 0.007 and the relative risk for these alleles was evaluated higher than 1. Conclusions: The results suggest that DQ8 is the dominant HLA-DQβ1 allele that is associated with susceptibility to RA in north-eastern Iran. [ABSTRACT FROM AUTHOR]

To assess the frequency of hyperprolactinemia and evaluate its possible clinical significance in patients with systemic lupus erythematosus (SLE). We determined serum prolactin (PRL) levels in 30 patients with SLE by a radioimmunometric assay. For each patient, the clinical disease activity was assessed using the Systemic Lupus Activity Measure. Antinuclear antibodies were determined by standard techniques. Correlation between PRL concentrations and SLE clinical and serological activity were evaluated. Elevated serum concentrations of PRL (>25 ng/ml in female and >16 ng/ml in male) were found in 10 of the 30 (33.3%) patients (7–85 ng/ml, mean 33.8, SD 19.8). A significant correlation was found between the PRL levels and the clinical disease activity of SLE ( P < 0.001, r = 0.675). In addition, hyperprolactinemia was associated with serological activity. Hyperprolactinemia was frequently detected in patients with SLE. There is a significant correlation between hyperprolactinemia and lupus activity. [ABSTRACT FROM AUTHOR]

Several data link vitamin D to many autoimmune diseases. Association between vitamin D receptor (VDR) gene BsmI polymorphisms and systemic lupus erythematosus has been reported. In this study, we examine whether the VDR gene BsmI polymorphisms are markers for susceptibility to or severity of SLE. This study incorporated 60 patients with SLE living in northeastern Iran. Three genotypes, BB, Bb and bb, were detected based on polymerase chain reaction–restriction fragment length polymorphism (PCR/RFLP). The distribution of VDR genotyping in patients with SLE was 23.3% for BB, 60% for Bb and 16.7% for bb and in the control group was 33.3% for BB, 46.7% for Bb and 20% for bb ( P = 0.334). No association of VDR gene BsmI polymorphisms with SLE disease activity index (SLEDAI), SLE damage score and major organ involvement was detected. The result of this study did not show any association between VDR gene BsmI polymorphisms and SLE. [ABSTRACT FROM AUTHOR]