ABSTRACT
Given the complexity of immune complex diseases including multiple sclerosis (MS) and the plausible interactions between different risk factors, delineating the interplay between them would be imperative. The current study aimed to evaluate the in vitro effects of Epstein-Barr virus (EBV) and vitamin D on immune response in MS patients and healthy controls. The status of vitamin D and EBV load was evaluated using multiple techniques. In vitro EBV-infected peripheral blood mononuclear cells (PBMCs), in the presence or absence of vitamin D, were checked for IL-10, IFN-γ, and vitamin D receptor. MS patients showed significantly higher plasma levels of 1,25-(OH)2D but not 25-OHD, increased EBV load, and lower levels of vitamin D receptor (VDR) expression compared with healthy controls. Interestingly, an inverse correlation was observed between VDR expression and EBV load in PBMCs. Indeed, the levels of IFN-γ and IL-10 production were significantly higher in supernatant collected from in vitro EBV-infected PBMCs in MS patients compared with controls. While all vitamin D-treated PBMCs showed reduced levels of IFN-γ production, in vitro treatment of vitamin D showed no influence in IL-10 production. EBV and vitamin D were found to exert opposite in vitro effects on immune dysregulation in these patients. Our results highlight the complex interactions of different risk factors with immune system.
Subject(s)
Epstein-Barr Virus Infections/complications , Multiple Sclerosis/immunology , Multiple Sclerosis/metabolism , Multiple Sclerosis/virology , Vitamin D , Adult , Cells, Cultured , Female , Herpesvirus 4, Human , Humans , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukin-10/immunology , Interleukin-10/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Male , Receptors, Calcitriol/metabolismABSTRACT
BACKGROUND: women of childbearing age are at higher risk for developing Neuromyelitis Optica Spectrum Disorder (NMOSD). Post-onset pregnancy is believed to affect and be affected by NMOSD. This study aimed to assess the effect of pregnancy on the development and course of NMOSD. METHOD: All women from the patient registry of the neurology outpatient clinic in Tehran, Iran, who were diagnosed with NMOSD without any comorbidity were enrolled in this survey. Retrospectively, the participants' reproductive history was collected, and the association of pregnancy-related factors with the age of onset, attack rate, and disability status was sought. RESULTS: The age at first attack was significantly higher in patients with prior pregnancy (P < 0.001). To eliminate the immortal time bias, the researchers assessed the effect of pregnancy as a time-varying exposure in the time-dependent Cox model, which indicated that pregnancy did not alter the time of developing NMOSD (Hazard Ratio=0.91, P = 0.741). However, more than one-fourth of patients with pregnancy before NMOSD onset had their first attack within the year of delivery. In addition, younger age at disease onset was accompanied by a shorter interval between the first pregnancy and first attack (Spearman's rho=0.826, P < 0.001). CONCLUSION: NMOSD onset or prognosis seemed not to be affected by pregnancy before the disease onset. However, in women with early disease onset, pregnancy might be a trigger for the development of NMOSD.