Mariette X, Agbalika F, Daniel M T, Bisson M, Lagrange P, Brouet J C, Morinet F
Service d'Immuno-Hématologie, Hôpital Saint-Louis, France.
Arthritis Rheum. 1993 Oct;36(10):1423-8. doi: 10.1002/art.1780361015.
To investigate whether human T lymphotropic virus type I (HTLV-I) could be involved in the pathogenesis of Sjögren's syndrome (SS).
Labial salivary gland (LSG) biopsy specimens from 9 patients with SS (4 with primary SS and 5 with SS secondary to rheumatoid arthritis) and 9 controls were studied for the presence of the tax gene of HTLV-I using in situ hybridization, and for the presence of tax, gag, pol, and env genes of HTLV-I using the polymerase chain reaction (PCR). Testing for antibodies to HTLV-I and examination of lymphocytes on blood smears were performed to determine whether systemic viral infection was present.
Using in situ hybridization and PCR, we detected the tax gene, but not the gag, pol, or env genes, of HTLV-I in LSG sections from 2 of 9 patients with SS and from none of the control subjects. Tax DNA was present mostly in nuclei of epithelial cells, but also in some lymphoid cells. Serum of the 2 affected patients did not contain antibodies to HTLV-I. In 1 patient, examination of blood smears revealed rare convoluted lymphocytes, sometimes with the appearance of "flower cells," as observed in the blood of HTLV-I-infected patients.
None of the known endogenous retroviral sequences is homologous to the tax gene. Thus, we suggest that HTLV-I (or another related retrovirus) can infect salivary epithelium. Transactivation properties of the tax protein could be implicated in the pathogenesis of SS. Alternatively, viral infection could cause de novo expression of HLA-DR antigens and favor the presentation of antigens by epithelial cells, leading, in some genetically predetermined subjects, to lymphoid infiltration of the gland.
研究I型人类嗜T淋巴细胞病毒(HTLV-I)是否参与干燥综合征(SS)的发病机制。
采用原位杂交技术研究9例SS患者(4例原发性SS和5例类风湿关节炎继发SS)及9例对照者的唇腺活检标本中HTLV-I的tax基因,采用聚合酶链反应(PCR)研究HTLV-I的tax、gag、pol和env基因。检测HTLV-I抗体并检查血涂片上的淋巴细胞,以确定是否存在全身性病毒感染。
通过原位杂交和PCR,我们在9例SS患者中的2例唇腺切片中检测到了HTLV-I的tax基因,但在对照者中均未检测到。gag、pol或env基因。Tax DNA主要存在于上皮细胞核中,但也存在于一些淋巴细胞中。2例受影响患者的血清中未含有HTLV-I抗体。在1例患者中,血涂片检查发现罕见的卷曲淋巴细胞,有时出现“花细胞”样外观,这在HTLV-I感染患者的血液中可见。
已知的内源性逆转录病毒序列均与tax基因无同源性。因此,我们认为HTLV-I(或另一种相关逆转录病毒)可感染唾液上皮。Tax蛋白的反式激活特性可能与SS的发病机制有关。或者,病毒感染可导致HLA-DR抗原的从头表达,并有利于上皮细胞呈递抗原,在一些具有遗传易感性的个体中,导致腺体的淋巴细胞浸润。