GABA Administration Ameliorates Sjogren’s Syndrome in Two Different Mouse Models

Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the salivary and lachrymal glands resulting in oral and ocular dryness. There are no clinically approved therapies to slow the progression of SS. Immune cells possess receptors for the neurotransmitter GABA (GABA-Rs) and their activation has immunoregulatory actions. We tested whether GABA administration has potential for amelioration of SS in NOD.B10-H2b and C57BL/6.NOD-Aec1Aec2 mice, two spontaneous SS models. Oral GABA treatment was initiated (1) after the development of sialadenitis but before the onset of overt symptoms, or (2) after the appearance of overt symptoms. When assessed weeks later, GABA-treated mice had greater saliva and tear production, as well as quicker times to salvia flow, in both SS mouse models. This was especially evident when GABA treatment was initiated after the onset of overt disease. This preservation of exocrine function was not accompanied by significant changes in the number or area of lymphocytic foci in the salivary or lachrymal glands of GABA-treated mice and we discuss the possible reasons for these observations. Given that GABA-treatment preserved saliva and tear production which are the most salient symptoms of SS and is safe for consumption, it may provide a new approach to help ameliorate SS.

ETIOPATHOGENESIS AND MANAGEMENT OF WAJAAL-MAFASIL (RHEUMATOID ARTHRITIS): AN EVIDENCE-BASED COMPREHENSIVE REVIEW

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetrical inflammatory polyarthritis involving small joints of the hand and feet. It has a global prevalence of 0.8 to 1% in Europe and the Indian subcontinent. Rheumatoid arthritis (Waja‘al-Maf?sil) had been broadly described and managed by the Unani scholars since antiquity. Many pharmacological and non-pharmacological treatment methods are available in the classical Unani literature. The treatment differs for different varieties of morbid humour involved in disease pathogenesis. Treatment aims to reduce morbidity and prevent disability, subsequently improving the quality of life. This review article mainly highlights the management of rheumatoid arthritis mentioned in classical Unani literature and supportive scientific evidence of various preclinical and clinical studies suggesting the potential of Unani medicine. This review article aims to explore the concept of rheumatoid arthritis in the Unani system of medicine to provide a better understanding of disease and its management through the holistic policy of Unani medicine. This review may conclude that Unani treatment can form an alternative source to manage RA.

Vitamin D and Omega-3 Polyunsaturated Fatty Acids in Type 1 Diabetes modulation

Background: Type 1 diabetes (T1D) is a chronic autoimmune disease that affects people globally. Usually developed during childhood, T1D is characterized by the destruction of pancreatic β-cells due to immune cell attack and the establishment of an inflammatory process. Objective: The study aimed to investigate the effects of vitamin D through its nuclear receptor and the ω-3 polyunsaturated fatty acids (PUFAs) through their lipid derivatives in T1D modulation. Both components exert anti-inflammatory activity and act directly on cells of the immune system, attenuating the destruction of insulin-producing cells. Furthermore, they lead to a better glycemic level, reducing the need for insulin and a normal immune state, such as C-peptide maintenance. Method: Presently, our review highlights the significant studies that evaluated the supplementation of vitamin D and ω-3 PUFAs in humans and animal models in the modulation of T1D. Conclusion: The data collected suggests that supplementation can provide potential benefits, mainly when done early in the diagnosis, since it reduces the need for insulin and the risk of complications generated by the disease.

Estrogen Receptors, ERK 1/2 Phosphorylation and Reactive Oxidizing Species in Red Blood Cells From Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with a significantly increased risk of cardiovascular mortality, mainly attributed to accelerated atherosclerosis. Methods: Thirty-two women (aged more than 18 years) with RA, and 25 age-matched healthy women were included in this study. Biomarkers of inflammation, red blood cells (RBCs) redox balance, estrogen receptor alpha (ER-α) expression as well as ERK 1/2 phosphorylation content were evaluated in RA patients at baseline and six months after treatment with disease modifying anti‐rheumatic drugs (DMARDs). Results: For the first times we demonstrated that in RA patients: i) disease activity score (DAS-28) positively correlated with RBC ER-α expression, and negatively with total antioxidant capacity of plasma; ii) RBC ER-α expression positively correlated with systemic inflammatory biomarkers and oxidative stress parameters as well as ERK 1/2 phosphorylation; and iii) DMARDs treatments improved the clinical condition measured by DAS-28 score decrease, although the RBCs appeared to be more prone to pro-oxidant status associated to the expression of survival molecules. Conclusion: Our data strongly suggest that RBCs could also participate in vascular homeostasis through fine modulation of an intracellular signal linked to the ER-α.

Clinical Significance of Serum Oxidative Stress Markers to Assess Disease Activity and Severity in Patients With Non-Segmental Vitiligo

Non-segmental vitiligo (NSV) is a chronic autoimmune disease characterized by progressive depigmentation of the skin. Oxidative stress (OS) has been proposed as one among the main principal causes in the development and establishment of a sustained autoimmune state in patients with NSV. However, the disease-associated OS biomarkers in clinical practice are not well studied. In this study, we found significantly reduced antioxidant enzymes [catalase (CAT) and superoxide dismutase (SOD)], total antioxidant capacity (TAC), and increased levels of lipid oxidation product malondialdehyde (MDA) and oxidative DNA damage byproduct [8-hydroxy-2-deoxyguanosine (8-OHdG)] in serum of NSV patients compared with healthy controls (HC). Serum TAC, MDA, and 8-OHdG levels were correlated with disease activity in all patients with NSV and much lower in patients receiving conventional treatment in the past 1 year compared to that without treatment. In addition, both serum MDA and 8-OHdG levels were significantly correlated with CXCL10 expression in patients with NSV. And the serum TAC, MDA, and 8-OHdG levels were also correlated with affected body surface area and Vitiligo Area Scoring Index score in patients with NSV. This study demonstrates dysregulated OS status in patients with NSV and provides the evidence that the serum TAC, MDA, and 8-OHdG have a capacity to indicate the activity and severity in patients with NSV.

Impacts of FcγRIIB and FcγRIIIA gene polymorphisms on systemic lupus erythematous disease activity index

Objective Systemic lupus erythematous (SLE) disease is a chronic autoimmune disease with unknown etiology that can involve different organs. Polymorphisms in Fcγ receptors have been identified as genetic factors in susceptibility to SLE. This study was aimed to investigate effects of two single nucleotide polymorphisms (SNPs) within FcγRIIB and FcγRIIIA genes on systemic lupus erythematous disease activity index (SLEDAI) in an Iranian population. Results Our findings indicated TT and GG genotypes were the common genotypes of FcγRIIB and FcγRIIIA SNPs in SLE patients, respectively. There were no significant differences in genotype and allele frequencies of FcγRIIB and FcγRIIIA SNPs in SLE and healthy subjects. However, the frequencies of genotypes and alleles of FcγRIIB and FcγRIIIA SNPs were significantly associated with some clinical manifestations used to determine SLEDAI (P < 0.001–0.5).

Severe neonatal autoimmune thrombocytopenia secondary to maternal Evans syndrome

Evans syndrome is a rare and chronic autoimmune disease seen in both paediatric and adult age groups. We present a case of severe thrombocytopenia in a neonate born to a mother with Evans syndrome who showed no response to intravenous immunoglobulin therapy initially and improved after treatment with methylprednisolone.

Cellular and Molecular Phenotypes of pConsensus Peptide (pCons) Induced CD8+ and CD4+ Regulatory T Cells in Lupus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with widespread inflammation, immune dysregulation, and is associated with the generation of destructive anti-DNA autoantibodies. We have shown previously the immune modulatory properties of pCons peptide in the induction of both CD4+ and CD8+ regulatory T cells which can in turn suppress development of the autoimmune disease in (NZB/NZW) F1 (BWF1) mice, an established model of lupus. In the present study, we add novel protein information and further demonstrate the molecular and cellular phenotypes of pCons-induced CD4+ and CD8+ Treg subsets. Flow cytometry analyses revealed that pCons induced CD8+ Treg cells with the following cell surface molecules: CD25highCD28high and low subsets (shown earlier), CD62Lhigh, CD122low, PD1low, CTLA4low, CCR7low and 41BBhigh. Quantitative real-time PCR (qRT-PCR) gene expression analyses revealed that pCons-induced CD8+ Treg cells downregulated the following several genes: Regulator of G protein signaling (RGS2), RGS16, RGS17, BAX, GPT2, PDE3b, GADD45β and programmed cell death 1 (PD1). Further, we confirmed the down regulation of these genes by Western blot analyses at the protein level. To our translational significance, we showed herein that pCons significantly increased the percentage of CD8+FoxP3+ T cells and further increased the mean fluorescence intensity (MFI) of FoxP3 when healthy peripheral blood mononuclear cells (PBMCs) are treated with pCons (10 μg/ml, for 24-48 hours). In addition, we found that pCons reduced apoptosis in CD4+ and CD8+ T cells and B220+ B cells of BWF1 lupus mice. These data suggest that pCons stimulates cellular, immunological, and molecular changes in regulatory T cells which in turn protect against SLE autoimmunity.

Vesiculobollous disease with Cutaneous Systemic Lupus Erythematosus Treated by Rituxima; a case report

SLE is a chronic autoimmune disease characterized by multisystem inflammation, Vesiculobullous (VB) are different groups of oral disorders characterized by the formation of bullae. The aim of this report is to describe a case of a vesiculobullous disease in SLE.

Altered Frequency and Phenotype of HLA-G-Expressing DC-10 in Type 1 Diabetes Patients at Onset and in Subjects at Risk to Develop the Disease

Type 1 diabetes (T1D) is a chronic autoimmune disease resulting in progressive destruction of β-cells. Several factors affecting lymphocyte and antigen-presenting cells, including dendritic cells (DCs), contribute to defective maintenance of tolerance in T1D. DC-10 are a subset of human DCs involved in IL-10-mediated tolerance. A precise monitoring of DC-10 in the peripheral blood is possible thanks to the discovery of specific biomarkers. DC-10, being cells that naturally express HLA-G, may be used for the appropriate staging of the disease. By enumerating and phenotypically characterizing DC-10 in the peripheral blood of subjects at different stages of T1D development—first-degree relatives (FDRs) of T1D patients, without (Abneg) or with (Abpos) autoantibodies, T1D patients at onset, and age-matched healthy controls (HCs)—we showed that DC-10 contain a high proportion of HLA-G-expressing cells as compared with monocytes. We reported that a low frequency of DC-10 during disease development is paralleled with the increased proportion of pro-inflammatory cDC2 cells. Moreover, DC-10 number and phenotype differ from Abneg FDRs, Abpos FDRs, and T1D patients compared with HCs, and DC-10 from T1D patients express low levels of CD83. Finally, multiple regression analysis, considering DC-10 and HLA-G-related parameters, showed that Abneg FDRs are more similar to subjects with autoimmunity than to HCs. This is the first demonstration that impairment in DC-10 number and phenotype, specifically CD83 expression, is associated with risk of developing T1D, suggesting a possible use of CD83+ DC-10 to stratify individuals at risk of T1D in conjunction with classical prognostic factors.