HTLV-ASSOCIATED DISEASES - HUMAN RETROVIRAL INFECTION AND CUTANEOUS T-CELL LYMPHOMAS

An array of neurologic, oncologic, and autoimmune disorders are associ ated with infection with the human pathogenic retroviruses human T-cel l leukemia virus types I and II (HTLV-I, II), as well as the human imm unodeficiency viruses (HIV). The cutaneous T-cell lymphomas, mycosis f ungoides (MF) and its hematogenous variant Sezary Syndrome (SS), share similar clinical and pathological features to HTLV-I-associated adult T-cell leukemia (ATL) and speculation of a retroviral link to MF and SS, especially in areas non-endemic for ATL, has lead to an intensifie d search for HTLV- and HIV-like agents in these diseases. To further e xplore a potential role for human retroviruses in MF and SS, skin biop sy-derived or peripheral blood mononuclear cell-derived DNA from 17 pa tients (MF, n=7; erythrodermic MF (EMF), n=5; SS, n=5) from the North Eastern United States were screened using gene amplification by PCR an d a liquid hybridization detection assay. Previously published primers and probes for HTLV-I (LTR, gag, pol, env, and pX), and our own prime rs and probes for HTLV-I (gag, pol, and env), HTLV-II (pol and env) an d HIV-I (gag and pol) were employed. Serum antibodies to HTLV-I were n egative in all but one EMF patient. The single HTLV-I seropositive pat ient carrying a diagnosis of EMF generated positive amplified signals for all of the eight HTLV-I regions tested. Ultimately, this individua l evolved to exhibit clinical manifestations indistinguishable from AT L. The other 16 patients were negative for all 12 HTLV and HIV retrovi ral regions. Our findings suggest that none of the known prototypic hu man retroviruses are associated with seronegative MF and SS. The unifo rmly positive results for HTLV-I in the seropositive patient suggests that this patient initially presented with a smoldering form of ATL an d illustrates the difficulty that sometimes may be encountered in the differential diagnosis of MF, SS, and ATL based solely on clinical and histopathological criteria.