Immunogenetics of human American cutaneous leishmaniasis. Study of HLA haplotypes in 24 families from Venezuela.

Twenty-four families with one or multiple cases of localized cutaneous leishmaniasis (LCL) from an endemic region with the highest incidence of LCL in Venezuela were typed from HLA-ABC, DR, DQ antigens and complement factors. The parental HLA haplotypes segregated at random among healthy and affected siblings but in backcross families significantly higher frequencies of HLA-A28 (p = 0.0018), -Bw22 (p = 0.0122), or -DQw8 (p = 0.0364) were present in affected compared to healthy siblings. HLA-B15 showed a higher frequency (p = 0.0062) among the latter group. Haplotypes Bw22CF31 (p = 0.0076) and Bw22DRw11DQw7 (p = 0.0163) were also significantly more frequent in affected compared to healthy siblings and A2Cw- (p = 0.0445) among the latter. No HLA genetic linkage with a putative LCL susceptibility gene(s) could be demonstrated in this study. A case/control comparison of 26 unrelated LCL patients (one proband from each family) and healthy individuals of the same ethnic origin confirmed the association of HLA-Bw22 (pc = 0.048) and -DQw3 (pc = 0.036) with LCL. The relative risk reached 12.5 for Bw22 and 4.25 for DQw3 with ethiologic factors of 0.17 and 0.64, respectively. HLA-DQw3 apparently makes the major contribution as a genetic risk factor for LCL at the population level.

Unique HLA-DR/DQ associations revealed by family studies in Warao Amerindians. Haplotype and homozygosity frequencies.

HLA-A, Cw, B and A, Cw, B, DR genotypes have been assigned, respectively, to 318 and 175 Warao Amerindians belonging to 73 sibships, who were tested with International Histocompatibility Workshop reagents. Only 33% of the theoretically possible three-loci and 7% of the possible four-loci haplotypes were found, with 10 and 6 of them accounting, respectively, for 75% of the total observed. This limited haplotype variability, expected in an inbred population, was not accompanied by either an increased or a decreased frequency of homozygous individuals, as demonstrated by population and family analysis. Inheritance of five HLA loci haplotypes in 20 families showed the expected distribution of parental haplotypes in sibling pairs. The study revealed DR2sh (DRw16), DR4 and DRw6 in association with DQw7, and DRw8 with DQw4, and significant positive linkage disequilibria between Bw62 CW1, B51 DRw16, B39 DR4, Bw62 DRw6, and DRw8 DQw4. The DR2-DQw7 and DRw6-DQw7 associations and the first three paired loci disequilibria mentioned are described for the first time in Amerindians and have not yet been found among Japanese, Negroid, or Caucasoid populations.

Cytotoxic antibodies in sera of Venezuelan multiparous women of Amerindian and mixed ethnic origin.

Sera from 464 multiparous women of mixed ethnic origin and 114 Amerindian mothers (Warao of Western Venezuela), were studied for lymphocytotoxicity using a panel of B and T lymphocytes isolated from 50 to 100 individuals from the same populations. Twenty-five and 9.65% of the sera, respectively, showed activity against at least 5% of the panel. Among the women of mixed ethnic origin 10% produced antibodies directed against one or more HLA Class I antigens while 2 sera contained monospecific anti-DR antibodies; among the Warao, only 2 sera recognized HLA antigens: a Bw51 and an undetermined Cw antigen which shows linkage disequilibrium with Bw16 in both populations.

HLA--D typing with homozygous cells identified in an American indigenous isolate. I. Population studies.

Lymphocytes from six individuals homozygous for their HLA--A, --B, --C and --D loci belonging to an American indigenous group, the Warao, have been used as typing cells to detect HLA--D determinants in 121 donors from the same indigenous isolate and in 71 donors of mixed ethnic origin living in Venezuela. Two determinants responsible for strong proliferation in mixed lymphocyte cultures have thus been identified. Four HLA--A2, B5 cells (r values between 0l72 and 0.57) identify a determinant provisionally called LD5a showing a gene frequency of 0.30 among the Warao and of 0.09 among the population of mixed ethnic origin. The nearest B locus antigen to this new specificity among the Warao is HLA--B5 (r value = 0.20). A second determinant identified by two HLA--A2, B15 sisters (r values of 0.71) shows a gene frequency of 0.15 among the Warao and of 0.03 among the mixed population. The latter is related to Dw8 as shown by results of the VI and VII Histocompatibility Workshops, and is weakly associated (r value of 0.28) to HLA--B15 among the American indigenous population tested.

Genetics of the HL-A system in a venezuelan heterogeneous population.

HL-A antigen and gene frequencies of 206 unrelated adults living in the cities of Caracas and Maracaibo have shown that this heterogeneous Venezuelan population sample possess 11 specificities of the first (LA) HL-A series and 15 specificities of the second (Four) series. HL-A2, HL-A9, HL-A5 and W5 showed frequencies higher than those observed in caucasoid populations. The most frequent haplotypes were 2, W5; 2, 5; 9, 12; 2, 12 and 2, X2. No outstandingly high value for gametic association between the alleles of the 2 HL-A series was observed, but haplotypes formed by antigens with dissimilar frequencies in Caucasoids, Negroids and American Indian tribes have shown statistically significant D values. Genetic distance calculated using the HL-A system alone showed that this population is closer to the average Caucasoid and Negroid population tested at the 5th International Histocompatibility Workshop than to 2 American Indian tribes living in the same country.