Hoftman Alice D C, Tai Lei-Qian, Tze Sheila, Seligson David, Gatti Richard A, McCurdy Deborah K
Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
J Rheumatol. 2008 Dec;35(12):2430-8. doi: 10.3899/jrheum.080333. Epub 2008 Nov 1.
Melanoma-associated antigen gene B2 (MAGE-B2) encodes an embryonic antigen normally silenced after birth except in testis and placenta. We identified the MAGE-B2 gene and autoantibodies in pediatric patients with systemic lupus erythematosus (SLE) glomerulonephritis. We investigated the prevalence of MAGE-B2 autoantibodies in association with active SLE, to determine a pathogenetic role of MAGE-B2 protein through its distribution in cells and tissues.
A cross-sectional study analyzed the frequency of MAGE-B2 autoantibodies in 40 patients with pediatric SLE, 23 adult controls, and 16 patients with pediatric juvenile rheumatoid arthritis (JRA) using Western blots containing recombinant MAGE-B2. SLE Disease Activity Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG) index measured SLE disease activity. Tissue distribution of MAGE-B2 protein was assessed by immunohistochemistry, immunofluorescence, and Western blots.
Seventeen (43%) of 40 pediatric SLE patients had MAGE-B2 autoantibodies as compared to 0 of 16 JRA patients and 2 of 23 adult controls. SLE disease activity was significantly higher in MAGE-B2 autoantibody-positive versus autoantibody-negative patients (SLEDAI-2K, mean 10.9 vs 5.2, p = 0.013; BILAG, mean 15.3 vs 6.3, p = 0.023). Active nephritis was more prevalent (60% vs 24%) in MAGE-B2 autoantibody-positive than autoantibody-negative SLE patients. MAGE-B2 protein was visualized in SLE kidney proximal convoluted tubules and in tumor epithelial cells, but not in lymphoblastoid cells.
MAGE-B2 autoantibody appears to be a clinically relevant biomarker for pediatric SLE disease activity and nephritis.
黑色素瘤相关抗原基因B2（MAGE - B2）编码一种胚胎抗原，该抗原在出生后通常会沉默，仅在睾丸和胎盘中表达。我们在患有系统性红斑狼疮（SLE）肾小球肾炎的儿科患者中鉴定出了MAGE - B2基因和自身抗体。我们调查了与活动性SLE相关的MAGE - B2自身抗体的患病率，以通过其在细胞和组织中的分布来确定MAGE - B2蛋白的致病作用。
一项横断面研究使用含有重组MAGE - B2的蛋白质印迹法分析了40例儿科SLE患者、23例成人对照和16例儿科幼年类风湿关节炎（JRA）患者中MAGE - B2自身抗体的频率。采用SLE疾病活动指数2000（SLEDAI - 2K）和英伦三岛狼疮评估组（BILAG）指数来衡量SLE疾病活动度。通过免疫组织化学、免疫荧光和蛋白质印迹法评估MAGE - B2蛋白的组织分布。
40例儿科SLE患者中有17例（43%）存在MAGE - B2自身抗体，而16例JRA患者中无，23例成人对照中有2例。MAGE - B2自身抗体阳性患者的SLE疾病活动度显著高于自身抗体阴性患者（SLEDAI - 2K，平均值分别为10.9和5.2，p = 0.013；BILAG，平均值分别为15.3和6.3，p = 0.023）。MAGE - B2自身抗体阳性的SLE患者中活动性肾炎更为普遍（60%对24%）。在SLE肾脏近端曲管和肿瘤上皮细胞中可观察到MAGE - B2蛋白，但在淋巴母细胞中未观察到。
MAGE - B2自身抗体似乎是儿科SLE疾病活动度和肾炎的临床相关生物标志物。
