IMMUNE ABNORMALITIES IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

系统性红斑狼疮患者的免疫异常

• 批准号: 3961230
• 负责人: A D STEINBERG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3961230
• 关键词: B lymphocyte; Sjogren's syndrome; T lymphocyte; autoantibody; autoimmune disorder; cell cell interaction; cell population study; flow cytometry; gene expression; helper T lymphocyte; hematopoietic stem cells; human subject; immunofluorescence technique; immunoglobulin G; immunologic assay /test; immunopathology diagnosis; immunoregulation; interleukin 2; kidney disorder; leukocyte activation /transformation; leukopenia; molecular pathology; monoclonal antibody; muscle disorders; nervous system disorder; oncogenes; orphan disease /drug; plaque assay; respiratory disorder; suppressor T lymphocyte; systemic lupus erythematosus; thrombocytopenia; tissue /cell culture

Patients with SLE have excessive B cell proliferation. They have increased proliferation of bone marrow stem cells and circulating B cell precursors. Disease activity is characterized by a switch from just proliferation to differentiation and immunoglobulin synthesis. In some patients the T cell regulation of B cell functions is abnormal. In an attempt to better understand cell-cell inter-actions, normals were studied for the capacity of T cells to respond to autologous non-T cells. IL 2 production by T4 plus cells was necessary for the proliferation of T8 plus (suppressor) cells. This function is subnormal in patients with SLE. Monoclonal antibodies were used to study subpopulations of SLE patients. One subset, with a reduced ratio of helper/suppressor cells, was characterized clinically by renal disease, thrombocytopenia, leukopenia and early age of onset of disease. Another subset had a high ratio and a clinical picture which included muscle and lung disease, Sicca syndrome, lympadenopathy and CNS disease. Thus, SLE may not be a single disease, but a group of syndromes with different genetic and cellular bases. SLE patients have a variety of T cell defects. These are largely explained by anti-T cell antibodies produced by the B cells of these patients. The more rapidly progressive autoimmune lymphorproliferative disorder, angioimmunoblastic lymphadenopathy is characterized by markedly effective helper T cells which drive B cells to proliferate and differentiate. The B cells themselves are normal in this varient. Proto-oncogene expression is abnormal in patients with SLE. There is a significant increase in expression characteristic of activated B cells.

SLE患者存在B细胞过度增殖。 他们增加了 骨髓干细胞和循环B细胞前体的增殖。 疾病活动的特征是从单纯的增殖转变为 分化和免疫球蛋白合成。 在某些患者中，T细胞 B细胞功能的调节异常。 为了更好 了解细胞间的相互作用，正常人的能力进行了研究 T细胞对自体非T细胞的反应。 通过T4产生IL 2 +细胞是T8+细胞增殖所必需的 细胞 SLE患者的这一功能低于正常。 单克隆抗体用于研究SLE患者的亚群。 一个亚群，辅助/抑制细胞的比例降低， 临床上以肾脏疾病、血小板减少症、白细胞减少症和 发病年龄较早。 另一个子集有很高的比率， 临床表现包括肌肉和肺部疾病，干燥综合征， 淋巴结病和中枢神经系统疾病。 因此，SLE可能不是一种单一的疾病， 一组具有不同遗传和细胞基础的综合征。 SLE患者存在多种T细胞缺陷。 这些在很大程度上解释了 由这些患者的B细胞产生的抗T细胞抗体。 自身免疫性淋巴增生性疾病进展越快， 血管免疫母细胞性淋巴结病的特征是 辅助性T细胞，其驱动B细胞增殖和分化。 B 细胞本身在这种变异中是正常的。 SLE患者原癌基因表达异常。 有一个 活化B细胞表达特征显著增加。