William A. Blattner

A Prospective Study of Human Immunodeficiency Virus Type 1 Infection and the Development of AIDS in Subjects with Hemophilia

We evaluated a multicenter cohort of 1219 subjects with hemophilia or related disorders prospectively, focusing on 319 subjects with documented dates of seroconversion to human immunodeficiency virus type 1 (HIV-1). The incidence rate of the acquired immunodeficiency syndrome (AIDS) after seroconversion was 2.67 per 100 person-years and was directly related to age (from 0.83 in persons 1 to 11 years old up to 5.66 in persons 35 to 70 years old; Ptrend = 0.00003). The annual incidence of AIDS ranged from zero during the first year after seroconversion to 7 percent during the eighth year, with eight-year cumulative rates (+/- SE) of 13.3 +/- 5.3 percent for ages 1 to 17, 26.8 +/- 6.4 percent for ages 18 to 34, and 43.7 +/- 16.4 percent for ages 35 to 70. Serial immunologic and virologic markers (total numbers of CD4 lymphocytes, presence of serum interferon or HIV-1 p24 antigen, and low or absent serum levels of anti-p24 or anti-gp120) predicted a high risk for the subsequent development of AIDS. Adults 35 to 70 years old had a higher incidence of low CD4 counts than younger subjects (P less than or equal to 0.005), whereas adolescents had a low rate of anti-p24 loss (P = 0.0007) and subjects 1 to 17 years old had a lower incidence of AIDS after loss of anti-p24 (P = 0.03). These findings not only demonstrate that the risk of AIDS is related directly to age but also suggest that older adults are disproportionately affected during the earlier phases of HIV disease, that adolescents may have a low replication rate of HIV, and that children and adolescents may tolerate severe immunodeficiency better because they have fewer other infections or because of some unmeasured, age-dependent cofactor or immune alteration in the later phase of HIV disease.

Mortality among chemical workers exposed to benzene and other agents

A historical cohort mortality study was conducted of 259 male employees of a chemical plant where benzene has been used in large quantities. The study group included all persons who were employed by the Company any time between January 1, 1947 and December 31, 1960. The cohort was followed through December 31, 1977 at which time 58 known deaths were identified. The only unusual finding was four deaths from lymphoreticular cancers when 1.1 would have been expected on the basis of national mortality rates. Three of the deaths were due to leukemia and one was caused by multiple myeloma. In addition, one of the leukemia deaths had multiple myeloma listed on the death certificate. The findings are consistent with previous reports of leukemia following occupational exposure to benzene and raise the possibility that multiple myeloma could be linked to benzene, also.

Waldenström's Macroglobulinemia and Autoimmune Disease in a Family

We diagnosed Waldenströms macroglobulinemia in a father and three offspring. Clinical and subclinical autoimmune disorders occurred excessively in the family. The HLA haplotype A2, B8, DRw3 was detected in all patients with Waldenströms macroglobulinemia and all but one family member with autoimmune manifestations. A lod score [log odds] of 4.86 favors linkage to the HLA complex of a gene predisposing to lymphoproliferative and autoimmune disorders. Associated with this HLA haplotype were the B-cell alloantigens Ia-172 and 350, previously reported in patients with the lymphoma-prone sicca syndrome.

Epidemiology of Multiple Myeloma and Related Plasma Cell Disorders: An Analytic Review

Publisher Summary This chapter presents an analytical review of epidemiology of multiple myeloma and related plasma cell disorders. A variety of etiologic factors may contribute to the development of multiple myeloma and related dyscrasias. The major risk indicator is age, with myeloma being especially common at older ages. Similarly, BMG also manifests a parallel old-age pattern, which may be etiologically related. In the postulated two hit mutation model, BMG may be one manifestation of the first hit, representing the controlled proliferation of a clone of plasma cell synthesizing the M-spike. The second hit occurs when another mutation leads to uncontrolled malignant proliferation. An age-dependent loss of regulatory cell function may be involved in the first hit by increasing the pool of terminally differentiated, immunoglobulin-secreting cells potentially available for malignant transformation. This old-age determinant may also help explain why an excess has not been found in some occupational and high-risk cohort studies which are limited in extent of long-term follow-up. Race is another important determinant. The higher rate and earlier age of onset of myeloma in Blacks suggests an inborn susceptibility, although environmental factors cannot be excluded. This may correlate with racial differences in baseline immunoglobulin levels 40 and with altered patterns of in vitro cellular response to mitogens in Blacks.

Multiple myeloma in the United States, 1950–1975

A total of 68,400 whites and 10,533 nonwhites were reported to have died from multiple myeloma (MM) in the continental United States between 1950 and 1975 (excluding 1972 because of incomplete case ascertainment). Age‐adjusted mortality rates for nonwhites were approximately twice as high as for whites. During the 25‐year period of this survey, there was a twofold to threefold increase in MM mortality. The increase was seen in both races, but was greater in nonwhites than whites and primarily occurred in people over 55 years of age. The increases were uniform in all geographic regions and urban/rural categories. MM mortality from 1950–1969 was correlated with geographic, demographic, and occupational factors at the county level. The rates were highest in the far west and mid‐central regions for whites and in the northeast for nonwhites. Urban areas had the highest rates and rural areas had the lowest, and positive associations were seen with indices of socioeconomic level and the percentage of residents with Scandinavian ancestry. For white males, MM mortality rates were elevated in areas with high petroleum and paper production, and a slight increase was seen in furniture manufacturing areas.

Cell surface antigens and function of monocytes and a monocyte-like cell line before and after infection with HIV

The human immunodeficiency virus (HIV-1) preferentially infects cells that express the CD4 molecule, including monocytes and cells of the monocyte lineage. The monocyte-like cell line U937 and monocytes isolated from peripheral blood lymphocytes (PBL) were infected with HIV-1. Cell surface antigen expression was determined in infected and noninfected cells as was the ability to stimulate in mixed lymphocyte reaction. The CD4 antigen decreased in infected cells U937 and PBL monocytes. MHC class II antigens HLA-DR, HLA-DQ, and HLA-DP increased in HIV-1 infected U937 cells. In infected PBL-derived monocytes, HLA-DR increased, HLA-DQ decreased, and HLA-DP was unchanged. Infected U937 and PBL monocytes were capable of stimulating allogeneic lymphocytes, thus demonstrating retention of the alloantigen presentation function of HIV-1-infected monocytes.

Human T-cell leukemia/lymphoma viruses: clinical and epidemiologic features

The discovery of the human T-cell leukemia/lymphoma virus (HTLV) family of retroviruses represents the culmination of a search that dates back more than 50 years, stimulated chiefly by the fact that leukemias and lymphomas in animals are often caused by retroviruses (Poiesz etal. 1980; Gallo and Wong-Stall 1982). Since the first virus isolation of HTLV in 1979, more than 100 isolates of human retroviruses, representing three distinet classes, have been reported from many laboratories in the world (Popovic etal. 1983b; Haynes etal. 1983; Miyoshi etal. 1981; Kalyanaraman etal. 1982b; Gallo etal. 1984). All of these isolates have an affinity to infect mature T cells and are, therefore, said to be T-lymphotrophic. The three classes of HTLV are termed HTLV-I, HTLV-II and HTLV-III. HTLV-I has been most thoroughly charac- terized from a molecular and clinical perspective and has been found to be associated with certain forms of mature T-cell leukemia/lymphoma, the description of which will be a major focus of this review (Blatnner et al. 1982; Gallo et al. 1983a; Blayney et al. 1983c). HTLV-II has more recently been isolated, and its relationship to human disease is unclear, although isolates have been obtained from a single patient with T hairy cell leukemia and from some patients with the acquired immune deficiency syndrome (Kalyanaraman et al. 1982b; Hahn et al., in press). In the latter case, it is likely that these isolations represented passenger viral infections, given the recent discovery of HTLV-III as the etiological agent for the acquired immune deficiency syndrome (AIDS) (Gallo et al. 1984). The molecular features of this class of viruses are reviewed elsewhere in this volume.

Screening of anti-HTLV antibody in sera of normal individuals and patients with malignancies in Taiwan

In the present study an immunofluorescence using KH-2 cells as target cells, has been developed for the screening of 1200 serum samples from normal individuals and 450 of cases from patients with various malignancies. The positive anti-HTLV-I antibody rate in the former group is 0.083% (1/1200) and while in the latter it is found to be 1.8% (8/450) (including 3 adult T-cell leukemia/lymphoma cases of the 92 hematopoietic and 5 of 358 non-hematopoietic malignancies). The differences between the two groups are found to be significantly different (p value is less than 0.0001). In addition to the 3 adult T-cell leukemia/lymphoma cases, the 5 seropositive cancer patients are of 5 different diseases. We have searched for the adult T-cell leukemia virus antigen and the p19 core protein in lymphoid cells of seropositive persons and the only positive cases were from cells of two proven adult T-cell leukemia (ATL) patients. Our results suggest that Taiwan is not an endemic area of adult T-cell leukemia virus and that KH-2 cells may be used for the detection of anti-HTLV-I antibodies.

The Influence of Race on T-Cell Subset Distributions

To investigate the influence of race on the cellular immune system, we analyzed peripheral blood mononuclear cell subsets in 266 healthy nonsmoking adults and 112 healthy children. Among adults, blacks had a significantly higher proportion of B cells, a lower proportion of T cells, and a higher proportion of HLA-DR positive cells and activated T cells than whites. Among children, the proportion of HLA-DR positive cells and activated T cells were significantly higher in blacks than in whites, but the proportion of T cells and B cells were similar in blacks and whites. An apparent decrease in the proportion of CD4+ (T-Helper) cells was observed in black women age 50 and older compared to white women and younger black women. These and other race-related immunologic alterations may provide clues to the etiology of diseases and conditions which exhibit significant racial differences.

Racial Variations in Immune Function and Hematological Parameters: Description of Study Design and Objectives

This paper describes a population-based study conducted by the National Cancer Institute which included the collection of blood from healthy black and white adults in the Washington, DC area and their children. For logistical reasons the initial survey excluded interviews with black smokers.