Increased seroreactivity to HERV-K10 peptides in patients with HTLV myelopathy

Raisa Perzova,Danielle Lalone,Elliot Graziano,Caitlin Welch,Thomas Loughran,Jordan Glaser,Swathi Sanghi,Bernard J Poiesz,Patricia Benz,William Sheremata,Lynn Abbott

doi:10.1186/1743-422x-10-360

Abstract

BackgroundPreviously, we had shown that persons infected with human T-cell lymphoma leukemia virus 1 or 2 (HTLV-1 or 2) had an increased prevalence of antibodies to a peptide in the Pol protein of the retrovirus HERV-K10, homologous to a peptide in HTLV gp21 envelope protein. The prevalence rate was higher in those with myelopathy vs. non-myelopathy. We have now extended our observations to a cohort restricted to North America in whom the diagnosis of HTLV myelopathy was rigorously confirmed to also test for reactivity to another HERV-K10 peptide homologous to the HTLV p24 Gag protein.MethodsSera from 100 volunteer blood donors (VBD), 53 patients with large granular lymphocytic leukemia (LGLL), 74 subjects with HTLV-1 or 2 infection (58 non-myelopathy and 16 myelopathy) and 83 patients with multiple sclerosis (MS) were evaluated in ELISA assays using the above peptides.ResultsThe HTLV myelopathy patients had a statistically significant increased prevalence of antibodies to both HERV-K10 peptides (87.5%) vs. the VBD (0%), LGLL patients (0%), MS patients (4.8%), and the HTLV positive non-myelopathy subjects (5.2%).ConclusionThe data suggest that immuno-cross-reactivity to HERV-K10 peptides and/or transactivation of HERV-K10 expression by the HTLV Tax protein may be involved in the pathogenesis of HTLV-associated myelopathy/tropical spastic paraparesis and spastic ataxia.

Highlights

In addition to causing T-cell malignancies, both human T-cell lymphoma/leukemia viruses 1 and 2 (HTLV-1 and HTLV-2) are known to cause myelopathy (HAM) in a minority of infected individuals [1,2,3,4,5,6]
In previous studies we had determined that, only 8% of patients with large granular lymphocytic leukemia (LGLL) were infected with HTLV-2, almost half the patients had antibodies to HTLV p24 Gag and gp21 Env proteins [13]. None of these patients were infected with HTLV-1, HTLV-3, HTLV-4, or bovine leukemia virus
The LGLL patients (0%) had significantly lower anti-HERV-K10 Gag seroprevalence rates than the volunteer blood donors (VBD) (7%), suggesting that this peptide may not be the target of the previously mentioned anti-HTLV p24 Gag reactivity observed in LGLL patients

Summary

Introduction

In addition to causing T-cell malignancies, both human T-cell lymphoma/leukemia viruses 1 and 2 (HTLV-1 and HTLV-2) are known to cause myelopathy (HAM) in a minority of infected individuals [1,2,3,4,5,6]. In previous studies we had determined that, only 8% of patients with large granular lymphocytic leukemia (LGLL) were infected with HTLV-2, almost half the patients had antibodies to HTLV p24 Gag and gp Env proteins [13]. None of these patients were infected with HTLV-1, HTLV-3, HTLV-4, or bovine leukemia virus. We had shown that persons infected with human T-cell lymphoma leukemia virus 1 or 2 (HTLV-1 or 2) had an increased prevalence of antibodies to a peptide in the Pol protein of the retrovirus HERV-K10, homologous to a peptide in HTLV gp envelope protein. We have extended our observations to a cohort restricted to North America in whom the diagnosis of HTLV myelopathy was rigorously confirmed to test for reactivity to another HERV-K10 peptide homologous to the HTLV p24 Gag protein

Methods

Results

Conclusion