ABSTRACT
AIM: To explore the expression of Sema4D, CD72 receptor and a role of Sema4D-CD72 signal in the control of immunocompetent cell function in remitting-relapsing multiple sclerosis (RRMS). MATERIAL AND METHODS: Fifty-two patients with RRMS diagnosis according to 2010 revised McDonald's criteria were studied. The control group included 24 healthy people. A flow cytometry method was used to measure the expression of semaphorin Sema4D by T-lymphocytes of peripheral blood, expression of CD72 receptor by B-lymphocytes, percentage of cells containing pro- and anti-inflammatory cytokines. The level of soluble Sema4D (sSema4D) was evaluated by ELISA. RESULTS: The level of Sema4D expression on T-lymphocytes (Mean Fluorescence Intensity - MFI) prevailed in cell subpopulations in patients with RRMS compared with the control group. Characteristics of membrane and sSema4D correlate with clinical presentations of the autoimmune disease. An increase in sSema4D level during cell cultivation was identified in RRMS patients. The results show the involvement of Sema4D in the hyperactivation of B-cell-mediated immunity through CD72 receptor and induction of proinflammatory cytokine synthesis. CONCLUSION: RRMS is associated with elevated expression of Sema4D in the immune system. Membrane and sSema4D involved in the pathological process in RRMS. The authors suggest several mechanisms of the involvement of semaphorin and its receptor in the pathogenesis of RRMS: the direct damage of nervous tissues by sSema4D penetrated through the blood brain barrier disrupted in RRMS or by membrane Sema4D due to the infiltration of the central nervous system by T-lymphocytes and hyperactivation of B-cell-mediated immunity.
Subject(s)
Antigens, CD/metabolism , Antigens, Differentiation, B-Lymphocyte/metabolism , Multiple Sclerosis, Relapsing-Remitting/immunology , Multiple Sclerosis, Relapsing-Remitting/pathology , Semaphorins/metabolism , Blood-Brain Barrier , Humans , Lymphocytes/immunology , Lymphocytes/metabolism , Lymphocytes/pathology , Multiple Sclerosis, Relapsing-Remitting/metabolismABSTRACT
Two cases of clinical and MRI manifestations of genetically verified CADASIL syndrome in female patients under 40 years of age are presented. The primary misinterpretation of clinical data and the neuroimaging results within multiple sclerosis indicates a lack of awareness of radiologists and neurologists about this disease. The article reviewed the current literature on the problems of diagnosis and treatment of CADASIL. The clinical and neuroimaging pattern of the syndrome, the approaches to genetic testing and the basic principles of patient management are considered in detail.
Subject(s)
CADASIL/diagnosis , Multiple Sclerosis/diagnosis , Adult , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging , NeuroimagingABSTRACT
The expression of class IV semaforin Sema4D and its CD72 receptor on lymphocytes was studied in patients with multiple sclerosis. The disease was associated with an increase in Sema4D level on intact T lymphocytes and with its more intense shedding from the membrane of activated cell. Multiple sclerosis was also associated with a decrease of CD72 receptor expression by B lymphocytes. Possible contribution of Sema4D to the disease development via the direct effects in the CNS and the immunomodulatory effect, specifically, B cell activity regulation, was discussed.
