The Role of Cobalamin on Interleukin 10, Osteopontin, and Related MicroRNAs in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Considering how vitamin B12 or cobalamin affects the immune system, especially inflammation and the formation of the myelin sheath, it appears as a complementary therapy for MS by affecting some signaling pathways. Recently diagnosed MS patients were divided into two groups (n=30). One group received interferon-beta (IFN-ß or Avonex), and another received IFN-ß+B12 for six months. Blood samples were taken before and after treatments.  Interleukin (IL)-10 and osteopontin (OPN) levels in the plasma were determined by the enzyme-linked immunosorbent assay (ELISA) method, and the expression of microRNA (miR)-106a, miR-299a, and miR-146a by real-time PCR. IFN-ß neither changed the IL-10 plasma levels nor miR106a and miR-299a expression, but it led to a remarkable decrease in OPN concentration and enhancement in let-7c and miR-146a expression. There was a significant decrease in IL-10, OPN plasma levels, miR-106a expression, and a substantial increase in let-7c and  miR-146a expression in IFN-ß+B12, treated group. There was no correlation between IL-10 and OPN with related miRNAs in the two treatment groups. Our study indicated that B12 could be a complementary treatment in MS that may influence the disease improvement.

Identification of Potential Biomarkers in the Peripheral Blood Mononuclear Cells of Relapsing-Remitting Multiple Sclerosis Patients.

Multiple sclerosis (MS) is described as an immune disorder with inflammation and neurodegeneration. Relapsing-remitting MS (RRMS) is one of the most common types of MS. The diagnostic manner for this disorder typically includes the usage of magnetic resonance imaging (MRI); however, this is not always a very precise diagnostic method. Identification of molecular biomarkers in RRMS body fluids samples compared to healthy subjects can be useful to indicate the normal and pathogenic biological processes or pharmacological responses to drug interaction. In this regard, this study evaluated different miRNAs in isolated peripheral blood mononuclear cells (PBMCs) of RRMS compared to controls and their correlations with altered T regulatory type 1 (Tr1) cells, osteopontin (OPN), and interleukin 10 (IL-10) levels. The frequency of Tr1 cells was measured using flow cytometry. Also, the expressions of different miRNAs were evaluated via quantitative real-time polymerase chain reaction (RT-qPCR) and plasma levels of IL-10 and OPN were tested by enzyme-linked immunosorbent assay (ELISA). The obtained results showed the Tr1 cells' frequency, Let7c-5p, and miR-299-5p levels decreased in RRMS patients to about 59%, 0.69%, and 20% of HCs, respectively, (P < 0.05). The miR-106a-5p levels increased about 7.5-fold in RRMS patients in comparison to HCs (P < 0.05). Moreover, the results showed that there was an increased negative association between Tr1 frequency and plasma-OPN levels in RRMS patients in comparison to HCs and also, we found a moderate positive correlation between plasma-IL-10 and miR-299-5p expression of RRMS patients. Overall, it may be possible to use these biomarkers to improve the diagnostic process. These biomarkers may also be considered for clinical and therapeutic studies in the future.

Spermatozoa Induce Maternal Mononuclear Cells for Production of Antibody with Cytotoxic Activity on Paternal Blood Mononuclear Cells.

OBJECTIVE: The maternal immune response to paternal antigens is induced at insemination. We believe that pregnancy protective alloantibodies, such as anti-paternal cytotoxic antibody (APCA), may be produced against the paternal antigens in the context of stimulated immunity at insemination and that they increase during pregnancy. APCA is necessary for pregnancy. It is directed towards paternal human leucocyte antigens (HLAs) and has cytotoxic activity against paternal leucocytes. The present study aims to determine whether APCA is produced by the maternal peripheral blood mononuclear cells (PBMCs) in contact with the husband's spermatozoa and to evaluate the relation of APCA production with HLA class I and II expressions by spermatozoa in fertile couples. MATERIALS AND METHODS: This cross-sectional study included 30 fertile couples with at least one child. The maternal PBMCs were co-cultured with the husband's spermatozoa and the supernatant was assessed for the presence of IgG by ELISA. Cytotoxic activity of the supernatant on the husband's PBMCs was assessed by the complement-dependent cytotoxicity (CDC) assay. RESULTS: IgG was produced in all co-cultures, and the mean level of supernatant IgG was 669 ng/ml. The cytotoxic activity of the supernatant was observed in all the supernatant obtained from the co-cultures. The mean percentage of APCA in supernatant was 73.93%. CONCLUSION: Based on the results of this study it can be concluded that APCA may be a natural anti-sperm antibody (ASA), which can be produced during exposure to spermatozoa and may have some influence before pregnancy. Further research is required to determine the role of APCA before pregnancy.

Potential Role of Trace Elements (Al, Cu, Zn, and Se) in Multiple Sclerosis Physiopathology.

Multiple sclerosis (MS) is an unpredictable disease of the central nervous system. The cause of MS is not known completely, and pathology is specified by involved demyelinated areas in the white and gray matter of the brain and spinal cord. Inflammation and peripheral tolerance breakdown due to Treg cell defects and/or effector cell resistance are present at all stages of the disease. Several invading peripheral immune cells are included in the process of the disease such as macrophages, CD8+ T cells, CD4+ T cells, B cells, and plasma cells. Trace elements are known as elements found in soil, plants, and living organisms in small quantities. Some of them (e.g., Al, Cu, Zn, Mn, and Se) are essential for the body's functions like catalysts in enzyme systems, energy metabolism, etc. Al toxicity and Cu, Zn, and Se toxicity and deficiency can affect the immune system and following neuron inflammation and degeneration. These processes may result in MS pathology. Of course, factors such as lifestyle, environment, and industrialization can affect levels of trace elements in the human body.