COMPARATIVE ANALYSIS OF CLINICAL AND MOLECULAR IMMUNOLOGICAL PATHOGENESES IN SUBTYPES OF MULTIPLE SCLEROSIS IN JAPAN

多发性硬化（MS）分为两种亚型，1）常规MS（CMS），其中脱髓鞘病变散布在中枢神经系统中，和2）视脊髓MS（OSMS），其特征在于视神经和脊髓的选择性受累。1.本研究120例MS患者中CMS（60.8%）、OSMS（22.5%）、脊髓型MS（7.5%）、继发进展型MS（5.0%）和原发进展型MS（4.1%）。OSMS与CMS相比，无一进展; 2. OSMS脑脊液中CCR 5 + CD 4+细胞亚群%和IgG 1%明显降低，提示OSMS的Th 1免疫功能低下; 3. OSMS与CMS不同的病理特征是严重的组织破坏，明显的巨噬细胞浸润，以及免疫球蛋白和活化补体在血管中的沉积。4.寡克隆带中最具特征性的病变-5.对CMS患者脑脊液IgG进行噬菌体展示分析，结果显示，CMS患者脑脊液中与疱疹病毒高度同源的序列通常与患者IgG结合。7.间接免疫荧光法检测患者血清和小鼠脑组织中Vβ5.2+T细胞的表达，结果显示在OSMS及其高危组中，Vβ5.2+T细胞的表达具有特异性。血清自身抗体被命名为NMO-IgG，其显示与CNS微血管、软脑膜、软脑膜下组织和Virchow-Robin间隙结合。NMO-IgG 7对OSMS的早期诊断及其在发病机制中的作用有待进一步研究。

Multiple sclerosis (MS) is classified into two subtypes, 1)conventional MS (CMS) in which demyelinating lesions are disseminated in the central nervous system and 2)optic-spinal MS (OSMS) characterized by the selective involvement of the optic nerves and spinal cord. We investigated clinical and molecular immunological pathogeneses of these two subtypes in Japan.1.The percentages of MS subtypes in our 120 cases were as follows, CMS (60.8%), OSMS(22.5%), spinal MS(7.5%), secondary progressive MS(5.0%), and primary progressive MS(4.1%). In contrast to CMS, none of OSMS was progressive.2.The CCR5+CD4+cell subset% and IgG1% in the cerebrospinal fluid (CSF) were significantly lower in OSMS than in CMS, suggesting less Th1 immunity in OSMS.3.Pathological features of OSMS distinct from CMS were severe tissue destruction, marked macrophage infiltration, and deposition of immunoglobulins and activated complements in the blood vessels.4.The most characteristic lesions in oligoclonal bands-positive CMS were the periventricular lesions.5.Phage display analysis of CSF IgG in CMS showed that the sequences highly homologous to herpes viruses were commonly detected as the peptides bound to the patients'IgG.6.CDR3 spectratyping analysis in MS revealed a frequent expansion of Vβ5.2+T cell clones suggesting the importance of the T cells in the pathogenesis of MS.7.Indirect immunofluorescence method with patients' sera and mouse brain tissue demonstrated a unique staining pattern specifically seen in OSMS and its high-risk group. The serum autoantibody was named NMO-IgG, and it was shown to bind to CNS microvessels, pia, subpial tissue and Virchow-Robin space. Further studies are needed to analyze NMO-IgG7s useful for early diagnosis of OSMS and its role in the pathogenesis.