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Results for “Histocompatibility Testing”

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At least 523 records · Page 29Linked to original sources
PubMed2003

Autoimmune hepatitis following allogeneic PBSCT from an HLA-matched sibling.

A 7-year-old boy with acute lymphoblastic leukemia (ALL) in second remission received an allogeneic PBSCT from his HLA-matched sister. Acute grade II graft-versus-host disease (GVHD) resolved with corticosteroids. Chronic GVHD in the skin and oral mucosa at around day 60 responded to corticosteroids and cyclosporin A. At 6 months after the transplant, he developed hepatic dysfunction with elevated serum transaminases and gamma-globulin. Liver biopsy revealed chronic inflammation with lymphocytes and plasma cells in portal areas without destruction of bile ducts, suggesting autoimmune hepatitis. While rare, autoimmune hepatitis should be considered a potential long-term complication in patients with hepatic dysfunction in the late post-transplant phase.

Biopsy↗
PubMed2006

HLA-C mismatch is associated with inferior survival after unrelated donor non-myeloablative hematopoietic stem cell transplantation.

HLA-C matching is an important determinant of outcome after myeloablative unrelated donor (URD) hematopoietic stem cell transplantation. However, its importance in non-myeloablative stem cell transplantation (NST) is not known. We report a retrospective analysis of 111 patients who underwent URD NST, of whom 78 were 10/10 matched at HLA-A, B, C, DRB1, DQB1 and 33 were mismatched at one or more HLA-C antigen/allele (24 HLA-C only; nine HLA-C+other locus mismatch). Patients were conditioned with busulfan (0.8 mg/kg/day i.v. x 4 days) and fludarabine (30 mg/m(2)/day i.v. x 4 days). Graft-versus-host disease prophylaxis included cyclosporine/prednisone- or tacrolimus/mini-methotrexate-based regimens. HLA-C disparity did not impair engraftment. Median marrow donor chimerisms were >or=90% donor at day+30 and +100 in both groups. Overall survival at 2 years was 30% in HLA-C-mismatched and 51% in 10/10-matched patients (P=0.008). In Cox regression, HLA-C mismatch was an independent predictor of death (hazard ratio 1.85, P=0.04). Treatment-related mortality was higher in the HLA-C-mismatched group: 48 versus 16% (P=0.0001). Cumulative relapse incidence was 35% in the HLA-C-mismatched and 55% in the 10/10-matched cohort, P=0.09. HLA-C mismatch is associated with inferior survival after URD NST.

Adolescent↗
PubMed2006

Lack of isohemagglutinin production following minor ABO incompatible unrelated HLA mismatched umbilical cord blood transplantation.

While immune hemolysis due to donor isohemagglutinin (IH) production often complicates minor ABO incompatible peripheral blood hematopoietic stem cell transplantation (PBSCT), it is not known if this occurs with umbilical cord blood transplantation (UCBT). We compared IH production and hemolysis following minor ABO allogeneic PBSCT and UCBT. We reviewed 24 ABO minor incompatible allogeneic PBSCTs and 14 ABO minor incompatible UCBTs. Patients were evaluated for donor-derived IH by reverse ABO grouping. Evaluation of hemolysis was based on clinical and laboratory findings of anemia associated with increased RBC transfusion need, concomitant with the appearance of donor-derived IH. Of the 24 ABO minor incompatible allogeneic PBSCTs, 15 produced donor-derived IH from 6 to 88 days following transplantation, with seven of 15 patients exhibiting clinically evident hemolysis. There was no significant difference in days to leukocyte engraftment or infused CD34 cells in patients with or without donor-derived IH. None of the 14 patients receiving ABO incompatible UCBTs showed evidence of donor-derived IH following transplantation with a median follow-up of 60 days. We conclude that donor IHs are not produced in patients undergoing minor ABO incompatible UCBTs suggesting fundamental immunologic differences between allogeneic PBSCT and UCBT.

Adolescent↗
PubMed2001

Improving the outcome of unrelated donor stem cell transplantation by molecular matching.

Volunteer unrelated donor (VUD) stem cell transplantation is now a well-established procedure in the treatment for many haematological and other disorders. The improved success of this modality of treatment is related, in part, to the existence of large volunteer donor registries (with well characterized tissue typing), as well as to the improved understanding of the molecular factors that have an influence on transplantation outcome. It is clear that close attention to human leukocyte antigen (HLA) matching is essential in ensuring a satisfactory transplant outcome, however the extent to which donor-recipient pairs need to be matched is not yet clear. There is also an increased understanding that factors other than HLA do affect clinical outcome. The ability to perform high resolution molecular typing techniques has allowed researchers to begin assessing the significance of mismatches at particular loci against an otherwise matched background, and in this way highlight the effects of individual genetic factors on transplantation outcome.

Cytokines↗
PubMed1985

Impaired reticuloendothelial function in patients treated with methyldopa.

In about 20 per cent of patients taking the antihypertensive agent methyldopa, IgG autoantibodies form against red cells, but most such patients do not have hemolysis. The reason for this is uncertain; it does not appear to be explained by known characteristics of the autoantibody. Since antibody-dependent reticuloendothelial function is an important determinant of cell clearance, we measured reticuloendothelial function in nine patients taking methyldopa. We did this by measuring the rate of clearance of radiolabeled autologous red cells sensitized with anti-D alloantibody. Five patients had a positive direct antiglobulin test, and four did not. Only one patient had laboratory evidence of hemolysis. The patients without hemolysis had significantly impaired reticuloendothelial clearance. In contrast, the patient with hemolysis did not have impaired reticuloendothelial function. This study suggests that in patients taking methyldopa who have a positive direct antiglobulin test the absence of hemolysis may be caused by an impairment in reticuloendothelial function. That the drug itself may be responsible for the impairment is suggested by the occurrence of abnormal reticuloendothelial function in patients taking the drug who have a negative direct antiglobulin test.

Anemia, Hemolytic, Autoimmune↗
PubMed1998

TAP2 alleles in inflammatory arthritis.

Sixty patients with reactive arthritis (ReA) and 40 with rheumatoid arthritis (RA), were typed for H LA-B27 and class II antigens DR and DQ, and studied for TAP2 gene polymorphism in comparison with 60 healthy controls. TAP2 polymorphisms at positions 379, 565, 665, and 687 were analyzed using amplification refractory system-based PCR and polymorphisms at positions 386 and 651 using oligonucleotide hybridization. The frequency of the TAP2A/A genotype was 30%(12/40) in RA, in contrast to 13% (8/60) in the controls. This genotype was further associated with DRB1*04 positive RA (10/24, 42%, P=0.01), as well as the TAP2A allele (31/48, 65%, P =0.012). Thr/Thr dimorphism at TAP2 position 665 (24/40, 60%, P=0.024) and Stop/Stop dimorphism at TAP2 position 687 (24/40, 60%, P=0.024) were found to be increased in RA patients as compared to controls. When TAP2I/J polymorphism was studied, TAP2J positivity was found associated with the HLA-B27DR4-DQB1*0301-haplotype in ReA patients. 9/12 of these were positive as compared to 20/60 in random controls (P=0.010). Polymorphisms of the TAP2 gene were found to be associated with subgroups of RA and ReA patients with disease associated markers (e.g. TAP2A in DRB1*04 positive RA, or TAP2J in HLA-B27-DRB1*04-DQB1*0301 positive ReA). These may thus serve as additional markers of specific haplotypes associated with susceptibility to inflammatory arthritis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

HLA antigens in four Pacific populations with non-insulin-dependent diabetes mellitus.

HLA antigen distributions in persons with normal and abnormal glucose tolerance were compared in four Pacific populations. The populations included Melanesians from the Fijian Islands, Loyalty Islands and mainland New Caledonia and Polynesians from the Wallis Islands. HLA-DR results are provided for the first time for Pacific groups. In Polynesians, HLA-B22 was increased in frequency in patients with non-insulin-dependent diabetes mellitus and also in persons with impaired glucose tolerance. However, the association was not statistically significant when corrected for the number of antigens tested. A similar increase in HLA-B22, although not significant, was seen in each of the three Melanesian populations with abnormal glucose tolerance. No other consistent increase in any HLA antigen occurred in persons with abnormal plasma glucose concentrations.

Diabetes Mellitus↗
PubMed2002

Major histocompatibility complex susceptibility genes and immune thrombocytopenic purpura in Caucasian adults.

Immune thrombocytopenic purpura (ITP) is a heterogeneous disorder with wide variability in response rates to treatments including corticosteroids, splenectomy and intravenous immune globulins. The nature of the underlying predisposing causes for this autoimmune disorder are not known. We have HLA typed 71 adult Caucasian patients with chronic primary ITP, and compared the data with 750 control samples. In this association study, we were not able to identify a significant immunogenetic susceptibility factor for ITP with HLA class I and class II alleles. However, it appeared that there might be an association between HLA-A2 and ITP, particularly in female patients, who are the predominantly affected group; and HLA-A2 was also present at increased frequency in patients with chronic ITP progressing to splenectomy. These findings are reviewed in the context of other similar reported HLA studies in ITP. Further studies based on larger groups of patients will be necessary to identify genetic susceptibility factors for this disease.

Case-Control Studies↗
PubMed1974

Genetics of restricted antibodies to streptococcal group polysaccharides in mice. I. Strain differences of isoelectric focusing spectra of group A hyperimmune antisera.

The immune response of nine inbred and one outbred strain of mice to the streptococcal group A polysaccharide was investigated with respect to magnitude and restriction. Analytical isoelectric focusing served as a tool to estimate the degree of restriction of Group A polysaccharide-specific antibodies. It proved feasible to distinguish low and intermediate from high responder strains, and to delineate strain-specificity of isoelectric focusing spectra of the immune sera. For example, immune sera of BALB/c mice, restricted high responders, and of C57BL/6 mice, heterogeneous low responders, had distinct focusing properties. Responsiveness was a dominant autosomal genetic trait in C57BL/6 x BALB/c F(1) hybrid mice, irrespective of the maternal and the paternal genotype; the immune sera of these mice had their own, rather uniform isoelectric focusing spectra whereby structural genes of the low responder strain were expressed to predominant levels in 81% of the hybrids. Responsiveness in C57BL/6 x BALB/c F(2) progeny segregated into 79% high and 21% low responders, and showed no genetic linkage to the following characteristics: hair color, sex, H-2 type, and Ig allotype of the heavy chain. The isoelectric focusing properties of these immune sera indicated segregation into patterns like BALB/c mice (40%), F(1) hybrids (48%), and C57BL/6 mice (12%). Since this segregation is independent of any of the above criteria in these F(2) mice a regulatory gene(s) is postulated that controls the clonal pattern of the immune response.

Animals↗
PubMed1988

1987 Philip Levine award lecture. MHC haplotypes in biology and medicine.

(1) The MHC genes or genes within or near the MHC region are involved in the immune response. The polymorphism of the MHC loci can be used as markers for immune response because the recognition of antigens involves their interaction with the MHC antigens. Specific portions of an antigen bind to the polymorphic region of class II molecules. Identification of an MHC class II molecule with a peptide results in a lack of an immune response as a result of self-tolerance. Similarities, but not identity of these molecules, result in immune responses restricted by the variable region of the MHC (class II molecule). This also explains a high repertoire of alloreactive T-cells. (2) By virtue of their restriction of the immune response to foreign antigens that cross-react with self-antigen, the MHC genes or genes within or near the MHC region show an association with the autoimmune diseases. (3) Several alleles encoded by different MHC loci are found nonrandomly associated at the population level. The resulting haplotypes could predict identity of segments of chromosome 6 among unrelated persons. (4) Matching of nonrandomly associated alleles (extended haplotypes) can serve potentially for selection of donors for allotransplantation, especially of bone marrow. (5) Several diseases associated with alleles of the class II MHc loci, and at least in the case of the lack of response to hepatitis B vaccine, have been shown to be more significantly associated with extended haplotypes. In such cases, the extended haplotypes may contain a susceptibility MHC allele of a known MHC locus or may contain a susceptibility gene of a yet undiscovered locus.

Allergy and Immunology↗
PubMed2003

Taskforce 5: preimplantation genetic diagnosis.

The European Society of Human Reproduction and Embryology (ESHRE) Ethics Task Force sets out a recommended multidisciplinary approach to the application of preimplantation genetic diagnosis (PGD). The statement includes consideration of fundamental ethical principles, specific problems in cases of high genetic risk, and PGD for aneuploidy screening, HLA typing and sex selection for non-medical reasons.

Aneuploidy↗
PubMed2004

Development and clinical application of a strategy for preimplantation genetic diagnosis of single gene disorders combined with HLA matching.

Preimplantation HLA matching has recently emerged as a tool for couples desiring to conceive a potential donor progeny for transplantation in a sibling with a life-threatening disorder. In this paper we describe a strategy optimized for preimplantation genetic diagnosis (PGD) of haemoglobinopathies combined with HLA matching. This procedure involves a minisequencing-based genotyping of HLA regions A, B, C and DRB combined with mutation analysis of the gene regions involved by mutation. Analysis of at least eight polymorphic short tandem repeat (STR) markers scattered through the HLA complex has also been included to detect potential contamination and crossing-over occurrences between HLA genes. The above assay can also be used for preimplantation HLA matching as a primary indication. The strategy was clinically applied for HLA matching in 17 cycles (14 for beta-thalassaemia, one for Wiscott-Aldrich syndrome and two for leukaemia). A reliable HLA genotype was achieved in 255/266 (95.9%) of the blastomeres. In total, 22 (14.8%) embryos were obtained that were HLA-matched with the affected siblings, 14 (9.4%) of which were unaffected and transferred back to the patients. Four clinical pregnancies were obtained, three of which (one twin, two singletons) are ongoing and were confirmed as healthy and HLA-identical with the affected children. Minisequencing-based HLA typing combined with HLA STR haplotyping has been shown to be a reliable strategy for preimplantation HLA matching. The major advantage of this approach is that the validation of a single assay can be done once and then used for the majority of the patients, reducing notably time needed for preclinical set-up of each case.

Blastocyst↗