Pathogenesis

TROPICAL SPASTIC PARAPARESIS/HUMAN T CELL LEUKEMIA TYPE 1-ASSOCIATED MYELOPATHY (TSP/HAM) PATHOGENESIS.

J. Casseb 1,2 and
A.C. Penalva-de-Oliveira 1,3

1 "Emílio Ribas" Institute of Infectious Diseases and
2 Clinical Allergy and Immunology Laboratory, Dermatology Department, College of Medicine, University of São Paulo, São Paulo, SP, Brazil
3 UPC - Clinical Research Unit on STD/AIDS, Infectious Diseases Division, Department of Internal Medicine, State University of Campinas, Campinas, SP, Brazil

Correspondence
J. Casseb
Laboratório de Alergia e
Imunologia Clínica
Departamento de Dermatologia
FM, USP
Av. Dr. Arnaldo, 455, Sala 2345
01246-903 São Paulo, SP
Brasil
Fax: +55-11-881-7190
E-mail: j31@hotmail.com

Research partially supported by
FAPESP (No. 99/11188-1) and CNPq
(No. 150115/98-9).

Received December 10, 1999
Accepted

SUMMARY

Tropical spastic paraparesis, also known as human T-cell leukemia type 1 -associated myelopathy (TSP/HAM), is caused by a human retrovirus called human T cells lymphotropic virus type 1 (HTLV-1), after a long period of incubation. TSP/HAM is characterized by a chronic and progressive paraparesis with sphincter disturbs, sensorial loss, lack of compression in the spinal column, and seropositivity for antibodies against HTLV-I. The pathogenesis for this virus is not well known, and involves the immune activation phenomenon against the presence of HTLV-I antigens, leading to an inflammatory process of demyelinization, especially in the thoracic spinal medulla. We could summarize the TSP/HAM pathogenesis in the following hypotheses: 1) presence of HTLV-I antigens in the lumbar spinal cord, noticed by the growth in viral load (DNA) for the HTLV-I; 2) lytic functions of the cytotoxic T lymphocytes (CTL) or production of soluble factors, such as the CC-chemokines, cytokines, and adhesion molecules; 3) presence of tax gene expression, activating the proliferating cells or inducing to an inflammatory process in the spinal cord; 4) presence of B cells, producers of neutralizing antibodies, or activation of the complement system, and 5) low production of IL-2, increase in IFN-g and the existence of a genetic factor involving some haplotypes from the major histocompatibility complex (HLA). All these factors are involved in the course of the TSP/HAM disease, and additional studies are needed in order to investigate the role of the immune system during the development of the TSP/HAM.