Grimaldi Christine M
Department of Medicine, Columbia University, 1130 St. Nicholas Avenue, New York, NY 10032, USA.
Curr Opin Rheumatol. 2006 Sep;18(5):456-61. doi: 10.1097/01.bor.0000240354.37927.dd.
For many decades, it has been speculated that sex hormones play a role in systemic lupus erythematosus. Recent data accumulated during the past few years provide striking evidence that hormonal modulation of B cells can have a profound impact on the survival, maturation and repertoire selection of autoreactive B cells and begin to explain the sex bias associated with the condition.
While there are still insufficient clinical data to define a role for estrogen or prolactin in human systemic lupus erythematosus, recent studies of anti-DNA antibody transgenic mice clearly demonstrate that an elevation in either estrogen or prolactin breaks tolerance of high affinity DNA-reactive B cells and induces a lupus phenotype. B cells with the same antigenic specificities are rescued by either estrogen or prolactin, but estrogen promotes the survival and activation of the T independent marginal zone B cell subset, while prolactin promotes the survival and activation of the T dependent follicular B cell subset.
Elevations in the levels of estrogen or prolactin can promote the survival and activation of high affinity autoreactive B cells. These hormones engage different B cell pathways to interfere with B cell tolerance. The identification of systemic lupus erythematosus patients with either an estrogen-responsive or prolactin-responsive disease will further the development of therapeutics that can specifically modulate hormonal responses.
数十年来，一直有人推测性激素在系统性红斑狼疮中发挥作用。过去几年积累的最新数据提供了显著证据，表明对B细胞的激素调节可对自身反应性B细胞的存活、成熟和库选择产生深远影响，并开始解释与该疾病相关的性别差异。
虽然目前仍缺乏足够的临床数据来确定雌激素或催乳素在人类系统性红斑狼疮中的作用，但最近对抗DNA抗体转基因小鼠的研究清楚地表明，雌激素或催乳素水平升高会破坏高亲和力DNA反应性B细胞的耐受性并诱发狼疮表型。具有相同抗原特异性的B细胞可被雌激素或催乳素挽救，但雌激素促进非T细胞依赖的边缘区B细胞亚群的存活和活化，而催乳素促进T细胞依赖的滤泡B细胞亚群的存活和活化。
雌激素或催乳素水平升高可促进高亲和力自身反应性B细胞的存活和活化。这些激素通过不同的B细胞途径干扰B细胞耐受性。识别出雌激素反应性或催乳素反应性疾病的系统性红斑狼疮患者将推动能够特异性调节激素反应的治疗方法的发展。
