Adamashvili Irena, Wolf Robert, Aultman Donnie, Milford Edgar L, Jaffe Stephen, Hall Vicky, Pressly Thomas, Minagar Alireza, Kelley Roger
Department of Surgery, Louisiana State University Health Sciences Center, P.0. Box 33932, Shreveport, LA 71130-3932, USA.
Rheumatol Int. 2003 Nov;23(6):294-300. doi: 10.1007/s00296-003-0306-3. Epub 2003 Jul 23.
Our objective was to study a possible contribution of major histocompatibility complex (MHC) genes to soluble HLA-I synthesis in patients with systemic lupus erythematosus (SLE). Solid-phase enzyme-linked immunoassay (ELISA) was used to measure sHLA-I in the sera of 20 patients with SLE and 76 normal controls with known HLA phenotypes. Serial serum samples ( n=108) from the above group of patients ( n=19) were further investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Soluble HLA-I levels were abnormally higher in patients with SLE than normal controls ( P<0.0002). No complete HLA haplotype has been identified to be correlated with high or low sHLA-I secretion. Only the sera of HLA-A23- or -A24- (splits of HLA-A9) positive individuals were found to contain high sHLA-I concentrations in both populations studied. The difference between sHLA-I of HLA-A24 patients ( n=7) and HLA-A24 normal controls ( n=19) was statistically highly significant ( P<0.0079). The results suggest that HLA-A24 may confer additional risk of more severe disease expression in female patients with SLE. The data imply that SLE patients carrying 39-kDa sHLA-I have increased risk of developing renal disease. A higher prevalence of 35-37 kDa was observed in patients with mild disease. Interestingly, 44-46 kDa was the predominant molecular form of sHLA-I in SLE patients with lymphocytosis with no evidence of organ involvement. Notably, all these variations were not reflected by differences in HLA phenotypes, with the exception of HLA-A24-positive patients, in whom the 44-46-kDa form occurs consistently but not exclusively. In summary, the results show a genetic heterogeneity of SLE with MHC control of the expression of sHLA-I concentrations and possible involvement of disease-associated factors that might potentiate a specific sHLA-I molecule synthesis.
我们的目的是研究主要组织相容性复合体（MHC）基因对系统性红斑狼疮（SLE）患者可溶性HLA - I合成的可能作用。采用固相酶联免疫吸附测定（ELISA）法检测20例SLE患者和76例已知HLA表型的正常对照血清中的可溶性HLA - I。对上述患者组（n = 19）的系列血清样本（n = 108）进一步采用十二烷基硫酸钠聚丙烯酰胺凝胶电泳（SDS - PAGE）和免疫印迹法进行研究。SLE患者的可溶性HLA - I水平异常高于正常对照（P < 0.0002）。未发现完整的HLA单倍型与高或低可溶性HLA - I分泌相关。在所研究的两个群体中，仅发现HLA - A23或-A24（HLA - A9的亚型）阳性个体的血清中可溶性HLA - I浓度较高。HLA - A24患者（n = 7）和HLA - A24正常对照（n = 19）的可溶性HLA - I差异具有高度统计学意义（P < 0.0079）。结果表明，HLA - A24可能使女性SLE患者出现更严重疾病表现的风险增加。数据提示，携带39 kDa可溶性HLA - I的SLE患者发生肾脏疾病的风险增加。在轻症患者中观察到35 - 37 kDa的发生率较高。有趣的是，在无器官受累证据的淋巴细胞增多的SLE患者中，44 - 46 kDa是可溶性HLA - I的主要分子形式。值得注意的是，除HLA - A24阳性患者外，所有这些差异均未通过HLA表型差异体现，在HLA - A24阳性患者中，44 - 46 kDa形式始终存在但并非唯一存在。总之，结果显示SLE存在遗传异质性，MHC控制可溶性HLA - I浓度的表达，并且可能涉及可能增强特定可溶性HLA - I分子合成的疾病相关因素。
