Biological Characteristic Of Myelin Oligodendrocyte Glycoprotein

BackgroundMultiple sclerosis (MS) is an autoimmune disease of the human central nervous system. Although MS used to be understood as a cell-mediated autoimmune disease, recent studies suggest a significant role of humoral response in MS pathogenesis. Among the variety of myelin proteins, MOG is considered the most promising candidate autoantigen in MS because that MOG can initiate both demyelinating autoantibody response and encephalomyelitis T cell response in Experimental autoimmune encephalomyelitis (EAE), an animal model for MS. However, since the year of1999, there had been lots of studies suggesting that there was no significant difference of positive percentage of anti-MOG antibody between MS patients and healthy controls. Consequently, researchers postulated that anti-MOG antibodies consisted of a group of antibodies, including pathogenic and nonpathogenic antibodies, and the attention turned to differentiate these two antibodies. Pathogenic and nonpathogenic antibodies recognized different MOG epitopes. The three main kinds of postulated epitopes recognized by pathogenic antibodies were linear epitopes, conformational epitopes and glycosylated epitopes. The researches on the linear epitopes were the one be studied thoroughly. There had been lots of references reporting specific linear epitopes in EAE and MS patients. Meanwhile, there were very few studies on the anti-MOG antibody in China, and no Chinese researcher paid their attentention to the linear epitopes of anti-MOG antibody. Studying on anti-MOG antibodies of Chinese MS patients makes the comparision between western countries and china possible, and at the same time fulfills the blank of the study on linear epitopes in China. Study on the biological characteristic and pathogenesis of MOG in MS patients may contribute to the understanding of the pathogenesis of MS in China, as well as providing the evidence for prediction of progression and therapy efficacy.ObjectivesThe objective of this research is to confirm anti-MOG antibody is prevalence in serum of Chinese people and to investigate the epitope specificity of anti-MOG antibodies in Chinese MS/NMO patients. Methods1. Clinical data collection:We collectted67MS/NMO patients (43Classic MS,10Opticospinal MS, and14NMO),60ONND patients from Neurology clinic and ward in PUMCH and77healthy controls (HC) from Healthy Center of PUMCH for one year (2009.4-2010.4). Age and sex ratio of the three groups of people were matched. After the concent form was signed, pheripheral blood was taken from all3groups of people and was kept at-20℃after centrifugation.We collected all the clinical data of MS/NMO patients, including detailed MS history, physical examination and EDSS, laboratory tests, imaging tests and therapy.2. Detection of anti-MOG antibody:ELISA was conducted using recombinant human MOG1～125aa as antigen to detect the anti-MOG antibodies in the3groups of people.3. Detection of specific epitopes of anti-MOG antibody:ELISA was processed using a panel of25synthetic biotinylated12aa long linear peptides with7aa overlaps corresponding to the sequence of extracellular domain of human MOG.4. The relationship between the pathogenic anti-MOG linear peptides antibody and the clinical data of MS/NMO patient was analyzed.Results1. No significant difference was found among the OD values of anti-MOG antibody in MS/NMO, ONND and HC serum (P>0.05). There were also no significant different titers of anti-MOG antibody in serum of cMS, OSMS and NMO (P>0.05).2. Linear epitopes amino-acid (aa)12-23(P<0.01)and27～38(P<0.01) were immunodominant in MS/NMO patients. According to ROC curve,27～38aa had better clinical value than12～23aa.3. Linear epitope97～108aa was immunodominant in ONND patients and Healthy people(P<0.01).4. Patients in relapse and with more relapse times had significantly higher percentage of anti-MOG27～38antibody than patients in remit or with less relapse times.5. The relapse rate of anti-MOG27～38antibody positive patients after INF-β treatment is lower than the antibody negative patients, but there was no significance. Conclusions1. Anti-MOG antibody can be found in different subtypes of MS patients, non-inflammatory neurological disease patients, as well as health people.2. Anti-MOG antibody have linear epitope specificity, linear epitopes amino-acid27～38aa and12～23aa were immunodominant in MS/NMO patients while97’108aa was immunodominant in ONND and HC.3. Epitope27～38aa has better clinical value according to ROC curve compared to12～23aa.4. Compared with anti-MOG27-38antibody negative patients, anti-MOG27～38antibody positive patients may have better efficacy when treated with INF-β.