Liu, Yisu (2018) T Cell repertoire and autoimmunity in multiple sclerosis patients in Sardinia. Doctoral Thesis.
Multiple sclerosis (MS) is an autoimmune disease characterized by destruction of the myelin sheath and axon loss within the central nervous system. Sardinia is a high-risk area of MS(multiple sclerosis). A genetically homogeneous population resulting from geographical isolation may be a critical factor that contributes to the high prevalence of the MS in Sardinia. It has been found that specific HLA genotypes in the Sardinian population are highly correlated with MS. The mechanism of how HLA impacts the adaptive immune response and triggers autoimmunity in the MS patient remains unknown. The total clonotypes of TCRs in one individual at a given time point is known as the T-Cell Receptor repertoire. By using next-generation sequencing, we have identified the TCR repertoire of MS patients in Sardinia, Italy. We found that MS patients have different TCR repertoires compared to those of healthy controls. MS-associated CDR3 sequences have been screened out in this study. BMLF-1 associated CDR3 are screened out in the MS-associated CDR3, indicating a higher activity of EBV in MS patients. TRBV20.1$TRBJ2.1 and TRBV20.1$TRBJ1.5 and other V-J recombinations show significant increases in MS individuals. These results suggest that the TCR repertoire may be a promising diagnostic method for disease status in MS patients. V-J recombination may be a biomarker for MS, especially in Sardinian people.
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