Identification of immunogenic epitopes of the 170-kDa subunit adhesin of Entamoeba histolytica in patients with invasive amebiasis.

Entamoeba histolytica causes amebic dysentery (AD) and liver abscess (ALA). Little is known about protective immunity to amebiasis, and studies in this area have been complicated by the paucity of defined ameba antigens. We examined the proliferative responses of peripheral blood mononuclear cells (PBMC) from patients with AD and ALA to a recombinant protein containing a portion of the 170 kDa adhesin of E. histolytica (170CR), and to two synthetic peptides (1 and 2) derived from the 170 kDa sequence that were predicted to contain T cell epitopes. A significant number of patients with AD and ALA had PBMC that proliferated to 170CR molecule, and several individuals with ALA and AD had T cells that recognized one or both peptides. Contrarily, individuals from a non-endemic region for amebiasis did not respond to 170CR protein, or to both peptides. In regard to antibody response, nine of fifteen patients with ALA showed antibodies to 170CR protein. These same patients had antibodies to peptide 2. We identified peptides from 170-kDa adhesin that may contain both T and B cell epitopes recognized by some patients with invasive amebiasis. These peptides may be valuable reagents in studies of the immune response to amebiasis.

HTLV-I maternal transmission in Martinique, using serology and polymerase chain reaction.

We have investigated HTLV-I and HTLV-II infection in children born to HTLV-I-seropositive or indeterminate Western blot mothers in Martinique by using the polymerase chain reaction (PCR). Only HTLV-I and no HTLV-II-positive samples were found in this study. All the samples from HTLV-I-seropositive children and adults were PCR positive, whereas the four HIV-I-seropositive and Western blot HTLV-I-negative mothers and their eight children were all PCR negative. Therefore, PCR and serology were in complete agreement in these patients. However, two of the six mothers who were first indeterminate by Western blot, and who later became seronegative, were found positive by PCR. Of the 27 children (ages 2-12 years), born to HTLV-I-seropositive and PCR-positive mothers, 2 were seropositive and PCR positive, 5 were seronegative and PCR positive with 2 primer pairs in gag and pol, and 4 were seronegative and PCR positive with only 1 of the primer pairs. In contrast to an initial rate of transmission of 7% estimated by serology we found a rate of transmission of 28 to 41% (whether or not children who were positive with only one of the primer pairs were included). Thus, our study confirms that PCR is useful in detecting HTLV-I infection in children before seroconversion and underlines the potential lack of sensitivity of serology to detect contaminating HTLV-I blood units in endemic areas.

HTLV-I infection in French West Indies: a case-control study.

A case-control study was performed in Martinique, French West Indies, comparing 66 anti-p24 antibody carriers to 91 seronegative subjects for HTLV-I, matched for age and place of residence. The aim of our study was to identify factors associated with HTLV-I infection and to observe whether clinical examination and biological measurements would reveal any abnormalities among the seropositive subjects. We observed a predominance of females among seropositive subjects (74% compared to 59%, p less than 0.05), and a greater risk due to earlier blood transfusions (p less than 0.001). This survey revealed important differences between cases and controls regarding socioeconomic factors: cases had fewer luxuries or advantages (i.e. bathroom, toilets, refrigerator, telephone, p less than 0.01), were more corpulent (p less than 0.05), and more often widowed, divorced or separated (p less than 0.01) than the controls. Although the differences were not significant, the seropositive donors seemed to be less educated, and were from a lower socioprofessional class than the seronegative donors. With regard to clinical symptoms (infections, adenopathies, splenomegaly, hepatomegaly) and biological parameters (blood count; T-cell subsets, electrophoresis of protids, immunoglobulins, calcemia, antischistosomal antibody), seropositive subjects appeared to be healthy; no parameters, except for alpha 1 globulin (p less than 0.05) and monocytes (p less than 0.05), were found to be correlated with seropositivity; but these two parameters remained within their normal ranges. This study confirms blood transfusion as a risk factor. It underscored the importance of socioeconomic factors for seropositivity.

HLA Gm systems and susceptibility to alcoholic cirrhosis: a study of mixed-race subjects.

The fact that only a small percentage of excessive drinkers develop cirrhosis may be due to a genetic susceptibility to the disease. In order to identify possible genetic risk factors for cirrhosis, we studied mixed-race (Negroid-Caucasian) inhabitants of the French West Indies and compared: (1) the frequency of 51 HLA-A, -B, -C and -DR antigens in 41 subjects with alcoholic cirrhosis and in two control groups consisting of 41 excessive drinkers free of liver disease and 51 healthy non-drinkers; and (2) the frequency of Gm and Km haplotypes in the same groups. Analysis of the Gm system also determined the patients' ethnic origins. The frequency of the HLA-A2 antigen was significantly higher in the cirrhotic patients than in the control group of excessive drinkers (chi 2 = 4.47; P less than 0.05), while that of the HLA-B15 antigen was significantly lower (chi 2 = 5.14; P less than 0.05). The frequency of the Cw4 antigen was significantly higher in the cirrhotics than in the non-drinkers (chi 2 = 5.59; P less than 0.05). However, these differences did not persist when the number of comparisons was taken into account. The frequency of Gm and Km haplotypes was not significantly different in the three groups. In conclusion, complementary studies are required to determine the value of the Gm-Km system as a marker of susceptibility to alcoholic cirrhosis. Our results do not identify an association between HLA antigens and cirrhosis specific to a negroid ethnic group and support the notion that such an association is weak.

Sex ratio of human T-lymphotropic virus type I infection and blood transfusion.

The prevalence of human T-lymphotropic virus type I (HTLV-I) infection is higher for females than for males. Blood transfusion is a potential confounding factor which might contribute to this high female:male ratio. Two studies were performed in Martinique (French West Indies) to clarify this issue: a case-control survey comparing the experience of previous blood transfusion among 62 HTLV-I-seropositive and 88 HTLV-I-seronegative blood donors, and a retrospective study of the sex of recipients of blood. Blood transfusion was strongly associated with HTLV-I infection (odds ratio = 6.4, p less than 0.001). Females were more often given blood transfusions (57.9 percent, p less than 0.001) and received a higher percentage of blood units (53.5 percent, p less than 0.05) than could be expected from their proportion in the general population (51.6 percent). Thus, the high female:male sex ratio of HTLV-I-infected subjects might be due partially to a sex difference for blood transfusion.

Anti HTLV-I antibodies and HLA phenotypes in the West Indies.

Sera of supposedly healthy blood donors were screened for the presence of anti HTLV-I p24 antibodies, and HLA typing for A, B, C and DR antigens was performed for 68 seropositive subjects and 92 seronegative controls. HLA phenotypes of the two groups were not significantly different but the level of the antibody response was related to the antigens of the HLA-B (P = 0.02) and -C loci (P = 0.003). Subjects with HLA-B12 or -B21 antigens had lower titres than the others. Subjects with HLA-Cw2 or -Cw7 antigens had higher titres than the others, but only the difference between HLA-B12 positive and negative subjects (P = 0.002) remained significant at the alpha = 0.10 level if the classical, although conservative, Bonferroni procedure was used to correct for the number of comparisons performed.

HLA A,B,C and DR association with insulin-dependent diabetes in Martinique.

HLA-A,B,C, and DR frequencies have been determined in 34 Coloured Martinican IDDM patients to establish the HLA and IDDM associations. HLA A3, B15, B18, Cw3 and DR4 antigens associations with IDDM are confirmed by this study. We found an increase of B21 similar to that found in Asiatic Indians. As in some African Black populations and in Cape coloured people, A1, B8, and DR3 are not increased in our population. We should point out that our patients' ages of onset were low, and that some studies have found DR4 association in young patients and DR3 in older ones. The protective role of DR2 is confirmed here. B35 and Cw4 negative associations have been found. We have observed that the antigens associated with IDDM are decreased in our control population, except DR4, and that the negative associated DR/ and Cw4 antigens are increased compared to the Continental French population. This corresponds with the low IDDM incidence in Blacks and Coloured people.

Study of HLA antigens in systemic lupus erythematosus in the French West Indies.

As incidence of SLE is high in Blacks, we studied HLA and SLE associations in the French West Indies, whose population is racially mixed. Forty-seven coloured SLE patients have been typed in HLA A,B,C and DR. We observed B8 association in nearly all of the studies. B15 association, more frequent in Caucasians, was found, also B53 association, a Black variant of B5 more frequent in Blacks. We did not find any class II association.

HLA antigens in 88 cases of rheumatic fever observed in Martinique.

HLA-A, B, C and DR antigens were studied in 88 patients from Martinique. A modest but significant reduction of B14 and Bw42 antigens was noted as well as an increase in B35 (p less than 0.05) and DR1 antigens (corrected p less than 0.05), two antigens known to be in linkage disequilibrium. These data, which corroborate a previous study for B35, suggest that the unusual antistreptococcal response mounted by rheumatic fever patients is under HLA control.

Study of HLA antigens of the Martinican population.

This is the first time a study has been undertaken on the HLA profile of the Martinican population, a population which is essentially the product of intermixture between African-Negroes and French Caucasians. Two hundred and thirty-eight nonrelated subjects were typed for the A and B loci, 158 subjects for C locus and 128 for DR locus. After analysis of our parameters (antigen and gene frequencies, linkage disequilibria, etc.) and their comparison to those found in the Black and Caucasian control populations, we came to the conclusion that our racially-mixed population is closer to the African-Negro population than to the French Caucasian. A study of the average gene flow enabled us to evaluate the Caucasian contribution as being about 30%. This figure is subject to change inasmuch as racial intermixture continues. Socio-cultural variables are assumed to play a minimal role, given the high rate of illegitimacy.

Antibodies to HTLV-I p24 in sera of blood donors, elderly people and patients with hemopoietic diseases in France and in French West Indies.

Human T-cell lymphoma/leukemia virus type I (HTLV-I) is a type-C retrovirus originally isolated from patients with leukemia or lymphoma involving mature T lymphocytes. Epidemiological studies have shown that HTLV-I infection occurs not only in leukemic but also in normal people in at least two areas of the world: the Caribbean basin and the South-West of Japan. We report here the results of a large seroepidemiological study of HTLV-I infection in normal French blood donors, elderly subjects living in institutions and patients with various malignant hemopathies, obtained by the classical HTLV-I p24 radioimmunoassay. We were unable to demonstrate antibodies to HTLV-I in 510 sera from French volunteer blood donors born and living in continental France or in sera from 262 blood donors born in other countries (mainly in Europe and North Africa) and living in continental France at the time of collection. In contrast, among 131 sera from blood donors born in French overseas territories (French Guiana, French West Indies, and Reunion) but living at the time of collection in continental France, 2 (1.5%) were found to possess anti-HTLV-I antibodies. In a sample of 2,597 blood donors from Martinique, 39 (1.5%) were positive. A positive correlation with age was observed whereas no statistical relationship was found between HTLV-I antibodies and sex, red cell blood groups or the place of residence in Martinique. On the other hand, a very high level of positive values was observed in Martinique among old people living in institutions, 14% of those aged over 60 years being positive. HTLV-I-associated hematological malignancies have not been observed in patients born and living in continental France whereas a large number exist in the French West Indies. In the same area, the presence of anti-HTLV-I antibodies in 12% of patients with myeloma, a typical B-cell disease, merits attention.

Is immunochemical determination of haptoglobin phenotype dependent?

Immunochemical methods have been used to determine the concentration of haptoglobins. The dependence on the phenotype was tested with highly purified Hp 2-1, Hp 2-2 and Hp 1-1, by immunonephelometry and radial immunodiffusion (RID). Measurements with three different instruments: automated immunonephelometer (AIP, Technicon), laser nephelometer (LN, Behring) and immunochemistry system (ICS, Beckman) were performed. For each type of apparatus antisera against a pool of haptoglobins were provided by the respective manufacturers. Some experiments were done with an antiserum to the haptoglobin heavy chain prepared in the laboratory. This study shows that haptoglobin determination depends neither on the physical geometry of the instruments or on the type of antiserum used in this work. In contrast, the data display a dependence on haptoglobin phenotype. When Hp 2-1, the most common phenotype, is taken as a standard, thd values obtained for Hp 2-2 are in good agreement with those obtained for Hp 2-1. However, the values obtained for Hp 1-1 are overestimated unless they are corrected by an experimental factor which has been determined in this study.