Tzioufas A G, Hantoumi I, Polihronis M, Xanthou G, Moutsopoulos H M
Department of Pathophysiology, Medical School, National University of Athens, Athens, Greece.
J Autoimmun. 1999 Dec;13(4):429-34. doi: 10.1006/jaut.1999.0333.
Recent studies have shown that minor salivary glands (MSGs) of patients with primary Sjögren's syndrome (pSS) are sites of anti-La/SSB autoantibody production. The aim of this study was to investigate the expression of La/SSB mRNA in MSGs of patients with pSS. La/SSB mRNA expression was studied by in situ hybridization in six biopsies of pSS patients with anti-La/SSB antibodies, nine pSS patients without anti-La/SSB and 10 patients with non-specific sialadenitis. Oligonucleotide probes corresponding to c-DNA encoding four linear epitopes of La/SSB (bp 423-471, bp 861-909, bp 903-954 and bp 1048-1092) were utilized. cDNA encoding linear epitopes of Ro52 (bp 786-837), Ro60 (bp 654-702) and the housekeeping genes of Sm and GAPDH were used as controls. The results were expressed as percent of positive cells by image analysis. Serum levels of anti-La/SSB autoantibodies were correlated with the presence and the intensity of La/SSB mRNA labeling. All pSS patients with anti-La/SSB antibodies in their serum expressed mRNA transcripts of epitopes 301-318 aa and 349-364 aa (encoded by the cDNA probes bp 903-954 and bp 1048-1092 respectively), predominantly in acinar and mononuclear cells of MSGs. These epitopes are the major targets of anti-La/SSB antibodies. Serum levels of anti-La/SSB antibodies were correlated with the number of positively stained cells in MSGs. Two of the nine pSS patients without anti-La/SSB autoantibodies and 2/10 non-pSS patients expressed the mRNA of the La/SSB molecule. The probes of RO52 and Ro60 epitopes did not react, while mRNA encoding the housekeeping genes of Sm and GAPDH was positive in all samples. In conclusion, pSS patients with anti-La/SSB antibodies showed upregulation of La/SSB mRNA in acinar and mononuclear cells of MSGs. Thus, active synthesis of La/SSB in MSGs of pSS seems to play an important role in the autoimmune response of the affected tissues.
近期研究表明,原发性干燥综合征(pSS)患者的小唾液腺(MSG)是抗La/SSB自身抗体产生的部位。本研究的目的是调查pSS患者MSG中La/SSB mRNA的表达情况。通过原位杂交技术,对6例有抗La/SSB抗体的pSS患者活检组织、9例无抗La/SSB的pSS患者以及10例非特异性涎腺炎患者的活检组织进行了La/SSB mRNA表达研究。使用了与编码La/SSB四个线性表位(bp 423 - 471、bp 861 - 909、bp 903 - 954和bp 1048 - 1092)的cDNA对应的寡核苷酸探针。编码Ro52(bp 786 - 837)、Ro60(bp 654 - 702)线性表位的cDNA以及Sm和GAPDH管家基因作为对照。结果通过图像分析以阳性细胞百分比表示。血清抗La/SSB自身抗体水平与La/SSB mRNA标记的存在及强度相关。所有血清中有抗La/SSB抗体的pSS患者均表达表位301 - 318 aa和349 - 364 aa的mRNA转录本(分别由cDNA探针bp 903 - 954和bp 1048 - 1092编码),主要在MSG的腺泡细胞和单核细胞中表达。这些表位是抗La/SSB抗体的主要靶点。血清抗La/SSB抗体水平与MSG中阳性染色细胞数量相关。9例无抗La/SSB自身抗体的pSS患者中有2例以及10例非pSS患者中有2例表达了La/SSB分子的mRNA。RO52和Ro60表位的探针未发生反应,而编码Sm和GAPDH管家基因的mRNA在所有样本中均为阳性。总之,有抗La/SSB抗体的pSS患者在MSG的腺泡细胞和单核细胞中显示La/SSB mRNA上调。因此,pSS患者MSG中La/SSB的活跃合成似乎在受影响组织的自身免疫反应中起重要作用。