Comparative analysis of two methods to detect donor-specific anti-HLA antibodies after kidney transplant.

Preformed anti-human leukocyte antigen (HLA) antibodies may be present in the blood of kidney transplant candidates. The production of these antibodies may occur in the post-transplant period, with the possible development of donor-specific antibodies (DSA). Luminex-based tests, such as the single antigen (SA) assay and the Luminex crossmatch (Xm-DSA) assay are the most commonly used tools to detect anti-HLA antibodies, due to their high sensitivity and specificity. This cross-sectional study aimed to compare the findings of two methods for the detection of DSAs after kidney transplant: SA and Xm-DSA. A total of 122 patients who underwent deceased donor kidney transplant at Hospital de Clínicas de Porto Alegre were included. The SA assay detected anti-class I HLA DSAs in 17 patients (13.9%) and anti-class II HLA DSAs in 22 patients (19.6%), whereas the Xm-DSA detected DSAs in 18 patients (14.8%) both against class I and class II antigens. There was agreement between the two methods for class I (kappa = 0.66, p = 0.001) and class II (kappa = 0.54, p = 0.025) antigens. The incidence of DSAs as obtained by the SA assay was 15.57%, and the most prevalent DSAs were those against HLA-DR antigens. Patient survival at 3 years was 92%. The two techniques assessed in this study provide important information on the presence of DSAs and may help in the post-transplant patient monitoring and in immunosuppressive strategy.

Blood chimerism in twins.

CONCLUSIONS: Chimerism is a phenomenon in which an individual has cells with different genetic content from different zygotes. In dizygotic twins (DTs), chimerism is believed to occur through placental anastomoses that enable the bidirectional exchange of hematopoietic stem cells. Little is still known about chimerism frequency in twins, but several studies have shown a relation between chimerism and some conditions such as autism, Alzheimer's disease, and a group of autoimmune diseases such as Sjögren syndrome, systemic lupus erythematosus, and systemic sclerosis. In addition to chimerism of ABO blood groups being possibly mistaken for ABO subgroups, these autoimmune diseases may affect other serologic immunohematologic tests. This study aimed to determine the frequency of chimerism in DTs through ABO and D testing using the tube method, column agglutination, and short tandem repeat (STR) assays. Among the 103 subjects assessed for this study, 24 subjects (12 pairs) were excluded because STR assays showed they were monozygotic; of the remaining, 70 subjects (35 pairs) were DTs and 9 subjects came from gestations of trizygotic triplets. No ABO or D chimerism was detected in any subject through serologic assays, and STR assays did not detect any blood chimerism. Although there was no evidence of chimerism found in this study, we emphasize the importance of observing the family background of individuals with suspected ABO subgroup in complex immunohematologic studies because ABO antigen-antibody reactions are similar in both circumstances, and chimerism can be overlooked. Moreover, the use of the STR analysis method in chimerism studies can be important to help differentiate chimerism and ABO subgroups.

Quantification of mixed chimerism allows early therapeutic interventions.

Hematopoietic stem cell transplantation is the curative option for patients with myelodysplastic syndrome; however, it requires a long post-transplantation follow-up. A 53-year-old woman with a diagnosis of myelodysplastic syndrome underwent related donor allogeneic hematopoietic stem cell transplantation in July 2006. Three months after transplantation, a comparative short tandem repeat analysis between donor and recipient revealed full chimerism, indicating complete, healthy bone marrow reconstitution. Three years and ten months after hematopoietic stem cell transplantation, the patient developed leukopenia and thrombocytopenia. Another short tandem repeat analysis was carried out which showed mixed chimerism (52.62%), indicating relapsed disease. A donor lymphocyte infusion was administered. The purpose of donor lymphocyte infusion is to induce a graft-versus-leukemia effect; in fact, this donor's lymphocyte infusion induced full chimerism. Successive short tandem repeat analyses were performed as part of post-transplantation follow-up, and in July 2010, one such analysis again showed mixed chimerism (64.25%). Based on this finding, a second donor lymphocyte infusion was administered, but failed to eradicate the disease. In September 2011, the patient presented with relapsed disease, and a second related donor allogeneic hematopoietic stem cell transplantation was performed. Subsequent short tandem repeat analyses revealed full chimerism, indicating complete bone marrow reconstitution. We conclude that quantitative detection of mixed chimerism is an important diagnostic tool that can guide early therapeutic intervention.

Quantification of mixed chimerism allows early therapeutic interventions

Hematopoietic stem cell transplantation is the curative option for patients with myelodysplastic syndrome; however, it requires a long post-transplantation follow-up. A 53-year-old woman with a diagnosis of myelodysplastic syndrome underwent related donor allogeneic hematopoietic stem cell transplantation in July 2006. Three months after transplantation, a comparative short tandem repeat analysis between donor and recipient revealed full chimerism, indicating complete, healthy bone marrow reconstitution. Three years and ten months after hematopoietic stem cell transplantation, the patient developed leukopenia and thrombocytopenia. Another short tandem repeat analysis was carried out which showed mixed chimerism (52.62%), indicating relapsed disease. A donor lymphocyte infusion was administered. The purpose of donor lymphocyte infusion is to induce a graft-versus-leukemia effect; in fact, this donor's lymphocyte infusion induced full chimerism. Successive short tandem repeat analyses were performed as part of post-transplantation follow-up, and in July 2010, one such analysis again showed mixed chimerism (64.25%). Based on this finding, a second donor lymphocyte infusion was administered, but failed to eradicate the disease. In September 2011, the patient presented with relapsed disease, and a second related donor allogeneic hematopoietic stem cell transplantation was performed. Subsequent short tandem repeat analyses revealed full chimerism, indicating complete bone marrow reconstitution. We conclude that quantitative detection of mixed chimerism is an important diagnostic tool that can guide early therapeutic intervention...

Lipoprotein lipase and APOE/APOC-I/APOC-II gene cluster diversity in native Brazilian populations.

Allele and haplotype frequencies for the T-93G, Hind III, and Pvu II variants of the lipoprotein lipase gene (LPL), and Hpa I and Ava II restriction site polymorphisms (RSP) of the APOE/C-I/C-II gene cluster were determined in 143 individuals from five Brazilian Indian tribes. These results were integrated with those previously reported for APOE. Marked interethnic variability occurs in these sites. A strong linkage disequilibrium was observed between the APOE and APOC-I loci (D' = 0.81; P < 0.00001). Linkage disequilibrium between the Hind III and Pvu II RSPs of the LPL gene was also observed (D' = 1; P < 0.001), but none of these RSPs were in linkage disequilibrium with the T-93G mutation. Considering both loci, heterozygosity was estimated as 0.45, but it was lower in the Xavante and Surui populations, in accordance with the historical and biodemographical data of these Amerindians. The results reported here may have implications for understanding interpopulation differences in lipid levels and coronary heart disease prevalences.