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Immunogenetic factors that may contribute to ethnic differences in renal allograft survival
1Transplant Laboratory, Durham Veterans Affairs Medical Center, North Carolina, USA.
Insights
African American kidney transplant patients face longer waits and poorer outcomes. Greater HLA (Human Leukocyte Antigen) diversity in African Americans, compared to Caucasians, may explain these ethnic disparities in kidney allograft survival.
Area of Science:
- Immunogenetics
- Transplantation immunology
- Health disparities
Background:
- Kidney transplantation is federally regulated for equal access, yet African Americans experience longer waits and poorer graft survival.
- Ethnic disparities in renal allograft survival are a significant concern in transplantation medicine.
Purpose of the Study:
- To investigate immunogenetic factors, including Human Leukocyte Antigen (HLA) diversity, contributing to ethnic differences in kidney allograft survival.
- To compare HLA antigen and haplotype frequencies between African American and Caucasian patient populations.
Main Methods:
- Analysis of ABO blood groups, HLA antigens, haplotypes, percent reactive antibody (PRA), age, and gender in a local patient population.
- Statistical comparison of HLA allele and haplotype frequencies between African American and Caucasian families.
- Assessment of HLA linkage disequilibrium using coefficient of contingency and Cramer's V statistic.
Main Results:
- No significant ethnic differences in PRA distribution were observed.
- Greater HLA polymorphism and more unique HLA haplotypes were found in African American families compared to Caucasian families.
- Higher HLA linkage disequilibrium was observed in Caucasians than in African Americans.
Conclusions:
- HLA antigen and haplotype polymorphisms are likely major immunogenetic factors contributing to ethnic differences in renal allograft survival.
- The greater diversity of HLA haplotypes in African Americans may influence allograft outcomes.
Abstract:
In the United States, allocation of cadaveric kidneys is federally regulated and based on the concept of equal access to all patients, regardless of race, sex, age, or socioeconomic status. Nevertheless, it has been widely reported that African American patients with renal disease wait longer for kidney transplantation and, once transplanted, have poorer graft survival. We have assessed immunogenetic factors that may contribute to ethnic differences in allograft survival by examining the distributions of ABO blood groups, HLA antigens and haplotypes, percent reactive antibody (PRA), age, and gender in our local patient population. Approximately 62% of patients at our transplant center waiting for renal transplantation are African American; 39% are female. Age distribution is comparable to that reported nationally. ABO blood groups of patients on the waiting list are distributed similarly to those reported nationally for other renal patients. Sensitization to HLA antigens, through either blood transfusion, prior transplant, or pregnancy, has been strongly associated with poorer graft survival. Although, as expected, distribution of PRA was significantly different for males versus females at one time point, it did not differ between ethnic groups in our patient population. HLA polymorphism was assessed by comparisons of HLA allele and haplotype frequencies determined by analyses of African American and Caucasian families typed in our program since 1991. Haplotypes observed in each ethnic population were subjected to a variety of statistical analyses. Coefficient of contingency and Cramer's V statistic (measures of degree of association) were consistently higher for Caucasian haplotypes than for those of African Americans. Significantly more unique HLA haplotypes were observed among African American families than among Caucasian families. Thus, our data provide evidence for greater HLA linkage disequilibrium in Caucasians than in African Americans. HLA antigen and haplotype polymorphisms are likely, therefore, to be major immunogenetic factors contributing to ethnic differences in renal allograft survival.