Detection of HTLV-I tax-rex and pol Gene Sequences of Thymus Gland in a Large Group of Patients With Myasthenia Gravis

Abstract

We report in this study the use of polymerase chain reaction (PCR) for the amplification of the genomic DNA, isolated from thymic tissue, using the primers flanking HTLV-I/II tax-rex genes and the sequence method to analyze the HTLV-I pol sequence of 27 Italian patients with myasthenia gravis. These molecular methods showed that 92.5% of patients tested positive for tax gene and 55% for pol genes; 55.5% samples were positive for both the tax gene of HTLV-I/II, and the pol gene of HTLV-I. Histologic investigation of the thymus showed that 15 samples had thymic hyperplasia, 93% tested positive for the tax gene, and 40% tested positive for both the tax and pol genes of HTLV-I. In contrast, 91.6% of thymoma-positive samples were positive for tax gene I/II and 75% positive for both genes, tax and pol type I. The sequence analysis of PCR product for tax and pol genes confirmed that these amplified products were HTLV-I, with minimal variations. Our date suggested that either HTLV-I or part of the virus genome is involved in the etiopathogenesis of myasthenia gravis.

Absence of human T-cell lymphotropic virus type I and human foamy virus in thymoma

“…Nonetheless, using samples obtained from US patients, we were unable to confirm prior reports that either HTLV-I or HFV DNA is present in thymoma tumour tissue (Saib et al, 1994;Liu et al, 1996;Manca et al, 2002).…”

“…The single prior report of HTLV-I detection in thymoma was from Italy (Manca et al, 2002). In that study, Manca et al tested thymic tissue from 27 patients with myasthenia gravis (12 with thymoma, 15 with thymic hyperplasia).…”

“…Specifically, HTLV-I sequences were amplified using SG231/SG238 for pol (239 bp product, nucleotide position 2802 -3038) (Ehrlich et al, 1990) and SK43/SK44 for tax (161 bp product, nucleotide position 7359 -7517) (Saito and Ichijo, 1992;Manca et al, 2002). Human foamy virus sequences were amplified using NC#8/PR#2 for gag (504 bp product, nucleotide position 3354 -3855) (Yu et al, 1999) and #5 0 bel1/#3 0 bel1 for bel1 (704 bp product, nucleotide position 10 182 -10 883) (Yu et al, 1996).…”

“…Additionally, sera from 83 other myasthenia gravis patients were studied by the same group (Manca et al, 2002). All were negative for HTLV-I/II antibodies by ELISA.…”

“…DNA sequences from human T-cell lymphotropic virus type I (HTLV-I), the viral cause of adult T-cell leukaemia/lymphoma, were detected in tumour tissue obtained from 11 Italian thymoma patients (Manca et al, 2002). Notably, HTLV-I infection is rare in Italy, and none of the patients had obvious risk factors for infection.…”