Vitamin E and Autoimmune Diseases: A Narrative Review

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

Calcitonin Gene-Related Peptide Effects on Phenotype and IL-12 Production of Monocyte-Derived Dendritic Cells in Rheumatoid Arthritis Patients

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 MethodsDCs 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.ResultsOur 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. ConclusionDecreased 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

H Syndrome Masquerade as Rheumatologic Disease

Background  H syndrome is an autosomal recessive genodermatosis with a low prevalence which is caused by a mutation in SLC29A3 gene. This disorder is characterized by sclerotic, hyperpigmented, hypertrichotic cutaneous plaques with systemic involvement including: hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height, and hyperglycemia. Case Presentation  Here we have presented two cases of H syndrome that have been misdiagnosed and mismanaged as rheumatologic disease. The first case had been represented with sclerotic skin lesions and diagnosed as morphea, and second one with chronic and recalcitrant to treatment arthritis as juvenile idiopathic arthritis. Conclusion  H syndrome is an autosomal recessive genodermatosis that has been recently recognized with a variety of manifestations and overlapping features with other diseases. Increase the knowledge of physicians for wide spectrum manifestations of this syndrome along with reporting the misdiagnosis of this condition can increase the accuracy of physicians for its better identification. This time our cases masquerade as rheumatologic diseases

ABO and Rh blood groups in patients with lupus and rheumatoid arthritis

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. Keywords: Rheumatoid arthritis (RA); Systemic lupus erythematosus (SLE); ABO blood group, Rh blood group

The genes expression status of inflammatory determinants following the oral administration of Mannuronic acid in patients with rheumatoid arthritis

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

A phase III, randomized, two-armed, double-blind, parallel, active controlled, and non-inferiority clinical trial to compare efficacy and safety of biosimilar adalimumab (CinnoRA (R)) to the reference product (Humira (R)) in patients with active rheumatoid arthritis

Background: This study aimed to compare efficacy and safety of test-adalimumab (CinnoRA (R), CinnaGen, Iran) to the innovator product (Humira (R), AbbVie, USA) in adult patients with active rheumatoid arthritis (RA). Methods: In this randomized, double-blind, active-controlled, non-inferiority trial, a total of 136 patients with active RA were randomized to receive 40 mg subcutaneous injections of either CinnoRA (R) or Humira (R) every other week, while receiving methotrexate (15 mg/week), folic acid (1 mg/day), and prednisolone (7.5 mg/day) over a period of 24 weeks. Physical examinations, vital sign evaluations, and laboratory tests were conducted in patients at baseline and at 12-week and 24-week visits. The primary endpoint in this study was the proportion of patients achieving moderate and good disease activity score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR)-based European League Against Rheumatism (EULAR) response. The secondary endpoints were the proportion of patients achieving American College of Rheumatology (ACR) criteria for 20% (ACR20), 50% (ACR50), and 70% (ACR70) responses along with the disability index of health assessment questionnaire (HAQ), and safety. Results: Patients who were randomized to CinnoRA (R) or Humira (R) arms had comparable demographic information, laboratory results, and disease characteristics at baseline. The proportion of patients achieving good and moderate EULAR responses in the CinnoRA (R) group was non-inferior to the Humira (R) group at 12 and 24 weeks based on both intention-to-treat (ITT) and per-protocol (PP) populations (all p values >0.05). No significant difference was noted in the proportion of patients attaining ACR20, ACR50, and ACR70 responses in the CinnoRA (R) and Humira (R) groups (all p values >0.05). Further, the difference in HAQ scores and safety outcome measures between treatment arms was not statistically significant. Conclusion: CinnoRA (R) was shown to be non-inferior to Humira (R) in terms of efficacy at week 24 with a comparable safety profile to the reference product

Acquired von Willebrand Syndrome in a Male with Systemic Lupus Erythematosus Presented with Mucocutaneous Bleeding and Treated with rFVIIa

Aubert Marcel. Varille (Mathieu) et Dr Loison. L'abbaye de Saint-Chef en Dauphiné, 1929. In: Bulletin Monumental, tome 88, année 1929. pp. 546-547