Immune Repertoires Of Systemic Lupus Erythematosus And Discoid Lupus Erythematosus

Objectives: Lupus erythematosus(LE)is a spectrum of classic chronic autoimmune diseases.It is mainly characterized by the failure of immune tolerance and abnormal activation of T and B lymphocytes as well as the generation of numerous autoantibodies,resulting in damage to target organs.70% ～ 85% of LE patients would experience skin lesions.According to the traditional view,systemic LE(SLE)and Discoid LE(DLE)are two ends of the LE spectrum respectively.Unfortunately,although many studies have shown that T and B cells play key roles in the pathogenesis of LE,the pathogenesis of SLE and DLE is still mysterious.Immune repertoire sequence(IR-Seq)is a new method to T/B cell research.It can help us fully reveal T and B cell diversity,clonal expansion and antibody spectrum maturation in adaptive immune response.In this study,IR-Seq was performed on the circulation and skin lesions of SLE and DLE patients to reveal the difference of skin damage mechanism of different LE and its relationship with systemic involvement,and to provide new ideas or new targets for clinical diagnosis and treatment of LE.Methods: A total of 10 SLE and 7 DLE patients were enrolled,and fresh skin tissue and peripheral venous blood were collected at the same time point.In addition,10 healthy volunteers were included and peripheral blood was collected as control.IR-Seq sequencing was performed on the peripheral blood and skin lesions of 17 LE patients and peripheral blood of10 healthy controls.The expression composition,V-J gene usage,diversity class switch recombination(CSR),somatic hypermutation(SHM)and clonal generation of TCR,BCR and their subtypes in each group were analyzed in detail.Besides,the association between skin lesion repertoire and peripheral blood repertoire was investigated.Results: We first observed more shared clones of u CDR3 s between peripheral blood and skin lesions in SLE patients than in DLE patients.Compared with SLE patients’ skin lesions,the expression of BCR and its subtype,the diversity of V-J recombination,the frequency of CSR and SHM,and the number of large clones were significantly increased in DLE patients’ skin lesions.Besides,we observed the significant increase of BCR expression and CSR,the existence of large clones,biased BCR subtype composition ratio,and the significant decrease in frequency of SHM in SLE patients’ peripheral blood.More important,we traced the isolated antibody mutation network in DLE patients’ skin lesion,which was independent from circulation;and the migration of antibodies from circulation to local tissues in SLE patients.Conclusion: DLE is a localized autoimmune skin disease characterized by abnormal activation of local B cells in skin,extremely active CSR and SHM,and a large number of local autoantibodies lead to skin lesions of immune damage.SLE is a systemic autoimmune disease in which circulating B cells are abnormally activated,pathologic CSR and SHM occur,and a large number of circulating autoantibodies are generated,which migrate into target organs and tissues then cause systemic immune damage.Therefore,the pathogenesis of DLE and SLE is quite different,in the aspect of immunology.