title: Thymic TFH cells involved in the pathogenesis of myasthenia gravis with thymoma.
abstract: Follicular helper CD4+ T (TFH) cells are the specialized providers of B cell help in germinal centers (GCs). Formation of GCs in thymi is the primary thymi characteristic in MG patients. TFH cells are involved in the pathogenic process of many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and autoimmune thyroid disease. The role thymic TFH cells played in MG with thymoma has not been elucidated. Here, we analyzed surface markers CXCR5, Bcl-6, ICOS and IL-21 on TFH cells in thymus derived from thymoma patients with ocular MG (OMG), generalized MG (GMG) or without MG using immunohistochemical staining, immunofluorescence, western blotting, and real-time PCR analysis. We show that clinical severity of MG is correlated with higher mRNA expression of the four markers. Indeed, results show higher expression of all four markers in thymoma with GMG patients compared with both OMG and non-MG patients. We found no significant difference in the expression of CXCR5, Bcl-6 and ICOS in OMG compared with non-MG patients. Regression analysis shows a positive correlation between thymic CXCR5, BCL-6, ICOS and IL-21 levels and quantitative MG score (QMGS) in GMG patients. In addition, we found no significant correlation between TFH cell expression and QMGS in OMG patients. Our findings show that higher expression of TFH cells in the thymoma is related to the clinical severity of MG and suggests a role in the pathogenesis of MG. However, the real source of these TFH cells is still uncertain and needs further study.
authors: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038,China.
authors: Min
authors: M
authors: Zhang
authors: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China.
authors: Yongan
authors: Y
authors: Zhou
authors: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038,China.
authors: Jun
authors: J
authors: Guo
authors: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038,China.
authors: Hongzeng
authors: H
authors: Li
authors: Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China.
authors: Feng
authors: F
authors: Tian
authors: Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China.
authors: Li
authors: L
authors: Gong
authors: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038,China.
authors: Xianni
authors: X
authors: Wang
authors: Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China.
authors: Miao
authors: M
authors: Lan
authors: Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038,China. Electronic address: lizhuyi@fmmu.edu.cn.
authors: Zhuyi
authors: Z
authors: Li
authors: Department of Pathology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, 710038, China. Electronic address: zhwlyh@fmmu.edu.cn.
authors: Wei
authors: W
authors: Zhang
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D009157:Myasthenia Gravis / Q000473:pathology* / Q000601:surgery; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D013934:Thymectomy; D013945:Thymoma / Q000473:pathology* / Q000601:surgery; D013950:Thymus Gland / Q000473:pathology* / Q000601:surgery; D013953:Thymus Neoplasms / Q000473:pathology* / Q000601:surgery; D000098546:Interleukin-21
chemical_list: C084103:BCL6 protein, human; C095085:CXCR5 protein, human; D004268:DNA-Binding Proteins; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D007378:Interleukins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D054380:Receptors, CXCR5; D000098546:Interleukin-21
keywords: Generalized myasthenia gravis; Ocular myasthenia gravis; T follicular helper cells; Thymoma; Thymus