Carl Saxinger

Multiple sclerosis and human T-cell lymphotropic retroviruses

A combination of different types of data suggests that some multiple sclerosis patients respond immunologically to, and have cerebrospinal T cells containing, a retrovirus that is related to, but distinct from, the three types of human T-cell lymphotropic viruses. The role of this virus in multiple sclerosis is uncertain.

Non-Hodgkin Lymphoma in Jamaica and its Relation to Adult T-Cell Leukemia-Lymphoma

Of 95 patients consecutively diagnosed with non-Hodgkin lymphoma, 52 (55%) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positivity was strongly associated with skin involvement, leukemia, and hypercalcemia (p less than 0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 9 patients had indolent courses and a median survival of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinant of adult T-cell leukemia-lymphoma.

HUMAN T-CELL LEUKAEMIA/LYMPHOMA VIRUS-ASSOCIATED LYMPHORETICULAR NEOPLASIA IN JAMAICA

19 (34%) of 56 Jamaicans with lympho-proliferative neoplasia had antibody to the human T-cell leukaemia/lymphoma virus (HTLV) in their sera. 17 of those positive had either non-Hodgkins lymphoma (NHL) or chronic lymphocytic leukaemia. Of 16 consecutive patients presenting with NHL, 11 (69%) were HTLV seropositive. Virus-positive patients with NHL, among whom females were over-represented, had the clinical features and poor survival typical of adult T-cell leukaemia/lymphoma. HTLV-associated leukaemia/lymphoma is a distinct clinicopathological entity, and the high incidence in this series suggests that HTLV is an important cause of lymphoreticular neoplasia in Jamaica.

Occurrence of human T cell lymphotropic virus (type I) antibodies in cutaneous T cell lymphoma

Of 315 patients from Scandinavia and West Germany with cutaneous T cell lymphoma, thirty-six (11.4%) had specific antibodies reactive against human T cell lymphotropic virus type I (HTLV-I). Among the HTLV-I antibody-positive patients, one had Sézary syndrome; five, mycosis fungoides, plaque stage; sixteen, mycosis fungoides, plaque stage with nondiagnostic histologic features; and three, lymphomatoid papulosis. All the patients from the Copenhagen area had several samples taken during the course of their disease, but the HTLV-I antibody titer was unaltered independent of the clinical stage the individual patient had at the time of the study. Eighty-three patients with non-Hodgkins lymphoma were tested for HTLV-I antibodies, and all except two showed negative results. The finding of specific antibodies reactive against HTLV-I in cutaneous T cell lymphoma suggests that a retrovirus related to HTLV-I plays an important role in the pathogenesis of cutaneous T cell lymphoma.

Molecular epidemiology of HTLV-I-Associated non-Hodgkin's lymphomas in Jamaica

As part of epidemiologic studies of human T‐lymphotropic virus (HTLV)‐I‐associated malignancies in Jamaica, the authors evaluated 26 patients with non‐Hodgkins lymphoma for the presence of integrated HTLV‐I provirus in their malignant cells. Fifteen of 26 patients had integrated provirus. All 15 also were HTLV‐I antibody positive. Eleven patients did not have integrated provirus, and all 11 were antibody negative. All of the antibody‐positive cases had onset of their disease in adulthood (age range, 21–57 years) as opposed to the broad age range of negative cases (4–66 years). Clinical features which were more common in provirus positive than negative patients included leukemic phase, skin involvement, and hypercalcemia, which are all features frequently seen in HTLV‐I‐associated adult T‐cell leukemia/lymphoma (ATLL). The presence of skin involvement, circulating malignant cells, abnormal liver function tests, or the presence of two or more of these four features were statistically significantly different between virus‐positive and virus‐negative cases. Although the survival of positive cases (6 months) was shorter than that of negative cases (9 months), this was not statistically significant. The only significant determinant of survival was hypercalcemia, with those who developed hypercalcemia at some point in their disease course, independent of their HTLV‐I status, surviving a mean of 5 months as compared to a mean of 17.5 months in those who never became hypercalcemic. The six HTLV‐I‐positive lymphomas that underwent cell typing were all primarily OKT4 positive, whereas two HTLV‐I antibody‐negative cases that were typed were B‐cell lymphomas.

Clinical evolution of cutaneous T cell lymphoma in a patient with antibodies to human T-lymphotropic virus type I

A woman who emigrated to the United States from the Dominican Republic developed the first signs of cutaneous T cell lymphoma during the last trimester of her pregnancy. This patient, found to have a positive reaction against human T-lymphotropic (leukemia-lymphoma) virus type I (HTLV-I), was followed up prospectively from the appearance of the initial skin lesion to the development of high-count helper T cell leukemia. Antibodies reactive with the core protein of HTLV-I were also identified in her husband and mother but not in her 2-year-old daughter. Examination of the patients course provides clues about the latency period and transmission of HTLV-I and highlights similarities between HTLV-I-positive and HTLV-I-negative cutaneous T cell lymphoma.

IMMUNE FUNCTIONS IN HTLV-III ANTIBODY POSITIVE HOMOSEXUAL MEN WITHOUT CLINICAL AIDS

This letter reports data on clinical and immunologic characteristics of 175 homosexual men living in Finland 15 (9%) of whom were anti-human T-lymphotropic virus type III (HTLV-III)-positive. Of the latter 2 had acquired immunodeficiency syndrome (AIDS) 5 had lymphadenopathy syndrome and 2 had enlarged lymph nodes but did not meet the criteria for lymphadenopathy syndrome. 27 homosexuals had a decreased T-helper: T-suppressor ratio characterized in the antibody-positive group by very low absolute T-helper cell counts and in the antibody-negative group by very high T-suppressor cell counts. Clinical and immunologic findings were similar to those in most cases of HTLV-III seropositivity although 1 man with lymphadenopathy-associated syndrome and 1 with symptoms suggestive of pre-AIDS has normal immunologic findings. In addition 2 men with lymphocyte stimulation aberrations became antibody negative and have remained symptom free througout the 10-month study period. During this 10-month follow-up no HTLV-III-antibody negative immunosuppressed man has shown seroconversion or acquired AIDS.

HTLV-I Antibodies Associated with Cutaneous T Cell Lymphoma in Denmark

The first isolation and characterization of a human retrovirus was done by Gallo and co-workers from patients with aggressive cases of adult T cell leukemia/lymphoma in the United States [15, 16]. This virus, named human T cell leukemia/lymphoma virus (HTLV-I) is a T cell-tropic retrovirus [8, 9], initially found sporadically among United States cases of adult T cell leukemias and lymphomas (ATLL) with cutaneous manifestations resembling aggressive variants of mycosis fungoides. Subsequently, HTLV-I was specifically linked to adult T cell malignancies in Japan and the Caribbean [8]. A second human retrovirus, HTLV-II, which is related to but distinct from all previous HTLV-I isolates, was identified and isolated from a patient with hairy cell leukemia [12]. Recently, a third retrovirus, HTLV-III has been isolated and is a probable etiologic agent in the acquired immune deficiency Syndrome (AIDS) [4–7].