Comparative analysis of the antibody response to the HTLV-I gag and env proteins in HTLV-I asymptomatic carriers and HAM/TSP patients: an isotype and subclass analysis.

We have compared the immunoglobulin isotype and IgG subclass and the titre of neutralizing antibody responses to the human T cell lymphotropic virus type I (HTLV-I) between a group of asymptomatic HTLV-I infected individuals and a group with the neurological disease HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). A western blot titration assay and an envelope peptide ELISA were used to determine the presence and titre of isotype and IgG subclass responses to the gag p19 and p24 proteins and to the envelope protein. Significant increases were observed in the number of individuals seropositive for a particular isotype and IgG subclass in the HAM/TSP group versus the asymptomatic group particularly for IgM and IgE and to a lesser extent, IgA. The predominant IgG subclasses to the HTLV-I p19, p24 and envelope proteins were IgG1 and IgG3. This finding was also observed in the titres of the antibody responses to these HTLV-I proteins. The HAM/TSP group also exhibited significantly higher neutralizing antibody titres than the asymptomatic group. This evidence suggests that some form of chronic immune stimulation might be involved in the immunopathogenesis of HAM/TSP. In addition, by following the Western blot titre to the IgM and IgE isotypes in particular, it may be possible to identify asymptomatic individuals progressing to HAM/TSP.

HTLV-1 antibody class and subclass distribution in African TSP and control populations.

The humoral immune responses in 44 sera from HTLV-1 seropositive African subjects were compared. The sample population was composed of 12 patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), 12 patients with other neurological conditions and 20 asymptomatic carriers. Samples HTLV-1 antigens were tested against all immunoglobulin classes and IgG subclasses, using the Western blot technique with polyclonal and monoclonal antibodies. Whilst IgG reacted with gag, env and tax products for the three groups studied, IgM and IgA were found to react more frequently with HTLV-1 in HAM/TSP patients. For these patients, IgM and IgA were particularly directed against tax and env proteins. Among IgG subclasses, IgG1 was most sensitive to gag, env and tax products reacting in similar proportions in all three groups. IgG2 and IgG4 were apparently not involved. IgG3 was most responsive in HAM/TSP patients. These data are similar to those observed in AIDS patients, LAS and HIV asymptomatic carriers and emphasize the role of HTLV-1 in HAM/TSP.

Immunoglobulin classes of antibody for human T-lymphotropic virus type-I (HTLV-I) in healthy donors and HTLV-I-associated disorders.

Healthy blood donors, patients with adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy (HAM) and recipients of unscreened blood (SR) who had seroconverted and were followed-up for more than 2 years were examined for HTLV-I antibodies of immunoglobulin G (IgG) and M(IgM) classes. The overall infection rate in donors was 4.9%, as determined by screening with a particle agglutination method (PA). The rate increased with increasing age. Positive sera with a low titer in the PA test (1/16, 1/32 and 1/64) contained IgM antibodies in 32.5% (titer 1/16) to 36.1% (titer 1/64) of the cases, but IgG antibodies were detected in only 5.6% of the sera with a titer of 1/16 and in 36.1% of the sera with a titer of 1/64. Conversely, in high titer sera (1/128 or higher) IgG antibodies were almost always detectable (99.0%) and IgM antibodies less frequently (25.5%). Sera from acute, chronic and pre-ATL, HAM and SR patients contained IgG antibodies in high titer in all cases. The incidence of IgM antibodies was 7.7, 30.0, 53.3, 72.3, and 77.8%, respectively. IgM antibodies were demonstrated repeatedly in some cases who were followed up for a year. Only IgM antibodies from HAM patients occurred in high titers and had strong reactivity to the p24 antigens of HTLV-I in Western blot testing. It is concluded that it is important to detect IgM antibodies not only in primary infections but also in persistent infections of HTLV-I.