https://scholars.lib.ntu.edu.tw/handle/123456789/159991
標題: | 狼瘡病人血清中抗中性白血球抗體的免疫活性,對應抗原的鑑定,及臨床應用(2/3) | 作者: | 余家利 | 關鍵字: | anti-neutrophil autoantibodies;bacter ial infection;neutropenia;systemic lupus erythematosus;SSB/La;抗中性球自體抗體;細菌性感染;中性球減少症;全身性紅斑狼瘡;抗SSB/La 抗體 | 公開日期: | 21-五月-2003 | 出版社: | 臺北市:國立臺灣大學醫學院分子醫學研究所 | 摘要: | 由於血清中有抗中性白血球抗體(anti-PMN antibodies)的存在,引起中 性球數目的減少以及功能上的缺陷,致使全身性紅斑狼瘡病人(SLE)易受 細菌的感染。然而SLE 病人血清中的anti-PMN 的對應抗原以及病理機轉 為何?在文獻上很少報告。在本研究中,我們以PMN cellular ELISA 法發 現約有20%的SLE 病人血清中含有anti-PMN 抗體。我們也發現在PMN 細胞表面的50kDa 分子為anti-PMN 抗體的對應抗原之一。以免疫抗體篩 選法,基因選殖及核甘酸序列分析證實50kDa 蛋白是為SSB/La 分子。我 們將活動性SLE病人的血清流經SSB/La-結合的親和性層析管柱純化出抗 SSB/La 抗體。本抗體會結合於PMN 細胞表面而後貫穿進入細胞內,引起 很多的生物活性,包括抑制吞食作用、加速細胞凋亡、以及增加IL-8 的 產生。這些生體外的結果顯示anti-SSB/La 抗體乃屬anti-PMN autoantibodies 的一種,會進入白血球內引起SLE 病人的白血球減少及機 能異常。 Decreased number and impaired functions of polymorphonuclear neutrophils (PMN) due to the presence of anti-PMN autoantibodies in the serum render patients with systemic lupus erythematosus susceptible to bacterial infections. However, the cognate antigens and pathological mechanisms of anti-PMN autoantibodies in SLE are rarely reported in the literature. In this study, we found approximately 20% of SLE sera contained anti-PMN autoantibodies detected by human PMN-coated cellular ELISA. A membrane protein with molecular weight of 50 kDa was identified as the cognate antigen of anti-PMN in Western blot after membrane-biotinylation and strptavidin column elution. The 50kDa molecule was proved to be SSB/La after immunoscreening, molecular cloning and nucleotide sequencing of the gene from the human leukocyte cDNA library. Human anti-SSB/La autoantibodies purified from active SLE sera passing through the recombinant SSB/La conjugated Sepharose 4B affinity column could bound and penetrate into normal human PMN. Functional analysis revealed that the anti-SSB/La autoantibodies exerted a number of potent effects on human PMN, including suppressed phagocytosis, accelerated apoptosis and enhanced IL-8 production. These in vitro results suggest that anti-SSB/La is one of the anti-PMN autoantibodies capable of penetrating into PMN and responsible for neutropenia and functional impairment of PMN in patients with SLE. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/23774 | 其他識別: | 912314B002129 | Rights: | 國立臺灣大學醫學院分子醫學研究所 |
顯示於: | 分子醫學研究所 |
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