Detection of human t lymphotropic virus type i tax gene in salivary gland epithelium from two patients with sjögren's syndrome

Abstract

Objective. To investigate whether human T lymphotropic virus type I (HTLV‐I) could be involved in the pathogenesis of Sjögren's syndrome (SS). Methods. 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. Results. 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. Conclusion. 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.

Absence of HTLV‐1tax in Sjögre's syndrome

“…It is possible that one of the regulatory genes of HTLV-I, the tax gene, causes inflammation by up-regulating cytokines. This hypothesis is supported by the report that mice transgenic for tax develop a sialadenitis similar to that of SS (2).…”

“…Mariette et a1 (2) reported that HTLV-I tax DNA was found by in situ hybridization in the salivary glands from 2 of 9 (22%) French patients with SS. Their subsequent PCR analysis demonstrated the HTLV-I tax gene in 9 of 40 (23%) patients (3).…”

“…hipping et a1 (1) and Goel et a1 (2) recently reported a failure to detect elevated levels of soluble Fas (sFas) in patients with human autoimmune disease. We believe the…”

Dry eye disease caused by viral infection: review

“…Salivary IgA antibodies to HTLV were found in seropositive HTLV patients with SS (22,23) . Indeed, two independent studies confirmed the presence of HTLV genome in salivary glands samples from patients with Sjögren (24,25) .…”

New evidence for involvement of retroviruses in sjögren's syndrome and other autoimmune diseases

“…An avian endogenous retrovirus has also been implicated in an autoimmune thyroid disease resembling Graves disease in chickens (32). As discussed above, other examples of the impact of germline retroviral gene expression relevant to the current discussion have been provided by the demonstration that tax transgenic mice develop symptoms resembling SS (2). In addition, transgenic mice expressing the HTLV-I env and tax genes develop chronic inflammatory arthropathy resembling rheumatoid arthritis (33).…”