ab2002

Prevalence of HTLV-I Tax in a subset of patients with rheumatoid arthritis

D. Zucker-Franklin, B.A. Pancake, W.H. Brown

New York University School of Medicine, New York City, New York, USA

ABSTRACT
Objective
In regions of the world where the human T cell lymphotropic virus type I (HTLV-I) is endemic, it is recognized that infection with this virus is associated with autoimmune diseases such as rheumatoid arthritis (RA).
Moreover, mice transgenic for the HTLV-I Tax gene develop a disease akin to RA. The observation that about 8% of healthy American blood donors carry HTLV-I Tax in their lymphocytes (1) prompted studies to determine whether Tax positivity is more prevalent among patients with RA and if so, whether its sequence is homologous with prototypic HTLV-I Tax. This proved to be the case. Of 102 patients with RA tested, one was a carrier of HTLV-I and 25 had the Tax sequences in their mononuclear cells and antibodies to p40 Tax in their sera, while being negative for antibodies to the structural proteins of the virus.

Methods
Blood was collected from 102 RA patients. Lysates of their mononuclear cells were assayed for HTLV-I Tax by PCR/Southern analysis, and in some positive cases Tax sequence analysis was performed. Antibodies to p40 Tax, the gene product of the Tax sequence, were detected by western blot assay using recombinant p40 Tax as antigen.

Results
Of the 102 patients tested, one proved to be a carrier of the virus, having antibodies and sequences for the viral structural proteins, gag and env in addition to p40 Tax. Twenty-five of the 101 HTLV-I/II seronegative patients carried both HTLV-I Tax sequences in their mononuclear cells and had antibodies to p40 Tax. Sequence analysis confirmed homology with HTLV-I Tax.

Conclusion
The data show that the prevalence of HTLV-I Tax positivity among patients with RA is ~3 times higher than among healthy blood donors. Since Tax is known to be involved in the development of numerous autoimmune diseases, the possibility that it is responsible for the development of RA in a subpopulation of patients with this disease is not remote.

Key words
Rheumatoid arthritis, HTLV-I Tax.

These studies were supported in part by grant R01-CA-58519 from the NIH and awards from The National Blood Foundation and The Mendik Foundation, to Dr. Zucker-Franklin.
Please address correspondence and reprint requests to: Dorothea Zucker-Franklin, MD, Department of Medicine TH 445, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.