Jucaud V, Ravindranath M H, Terasaki P I, Morales-Buenrostro L E, Hiepe F, Rose T, Biesen R
Terasaki Foundation Laboratory, Los Angeles, CA, USA.
Department of Nephrology and Mineral Metabolism, National Institute of Medical Sciences and Nutrition 'Salvador Zubirán', Mexico City, Mexico.
Clin Exp Immunol. 2016 Mar;183(3):326-40. doi: 10.1111/cei.12724. Epub 2015 Dec 16.
T lymphocyte hyperactivity and progressive inflammation in systemic lupus erythematosus (SLE) patients results in over-expression of human leucocyte antigen (HLA)-Ib on the surface of lymphocytes. These are shed into the circulation upon inflammation, and may augment production of antibodies promoting pathogenicity of the disease. The objective was to evaluate the association of HLA-Ib (HLA-E, HLA-F and HLA-G) antibodies to the disease activity of SLE. The immunoglobulin (Ig)G/IgM reactivity to HLA-Ib and β2m in the sera of 69 German, 29 Mexican female SLE patients and 17 German female controls was measured by multiplex Luminex(®)-based flow cytometry. The values were expressed as mean flourescence intensity (MFI). Only the German SLE cohort was analysed in relation to the clinical disease activity. In the controls, anti-HLA-G IgG predominated over other HLA-Ib antibodies, whereas SLE patients had a preponderance of anti-HLA-F IgG over the other HLA-Ib antibodies. The disease activity index, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000, was reflected only in the levels of anti-HLA-F IgG. Anti-HLA-F IgG with MFI level of 500-1999 was associated with active SLE, whereas inactive SLE revealed higher MFI (>2000). When anti-HLA-F IgG were cross-reactive with other HLA-Ib alleles, their reactivity was reflected in the levels of anti-HLA-E and -G IgG. The prevalence of HLA-F-monospecific antibodies in SLE patients was also associated with the clinical disease activity. Anti-HLA-F IgG is possibly involved in the clearance of HLA-F shed from lymphocytes and inflamed tissues to lessen the disease's severity, and thus emerges as a beneficial immune biomarker. Therefore, anti-HLA-Ib IgG should be considered as a biomarker in standard SLE diagnostics.
系统性红斑狼疮（SLE）患者的T淋巴细胞功能亢进和进行性炎症会导致淋巴细胞表面的人类白细胞抗原（HLA）-Ib过度表达。炎症时这些抗体会释放入循环系统，并可能增加促进疾病致病性的抗体产生。目的是评估HLA-Ib（HLA-E、HLA-F和HLA-G）抗体与SLE疾病活动度的相关性。通过基于多重Luminex®的流式细胞术检测了69名德国、29名墨西哥女性SLE患者及17名德国女性对照血清中针对HLA-Ib和β2m的免疫球蛋白（Ig）G/IgM反应性。结果以平均荧光强度（MFI）表示。仅对德国SLE队列进行了与临床疾病活动度相关的分析。在对照组中，抗HLA-G IgG在其他HLA-Ib抗体中占主导地位，而SLE患者中抗HLA-F IgG相对于其他HLA-Ib抗体占优势。疾病活动指数，即系统性红斑狼疮疾病活动指数（SLEDAI）-2000，仅反映在抗HLA-F IgG水平上。MFI水平为500 - 1999的抗HLA-F IgG与活动性SLE相关，而无活动性SLE则显示较高的MFI（>2000）。当抗HLA-F IgG与其他HLA-Ib等位基因交叉反应时，其反应性反映在抗HLA-E和-G IgG水平上。SLE患者中HLA-F单特异性抗体的患病率也与临床疾病活动度相关。抗HLA-F IgG可能参与清除从淋巴细胞和炎症组织中释放的HLA-F，以减轻疾病严重程度，因此成为一种有益的免疫生物标志物。所以，抗HLA-Ib IgG应被视为标准SLE诊断中的生物标志物。
