Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

73 consecutive patients with severe aplastic anemia were treated by marrow transplantation from hematologically normal HLA identical siblings. 68 patients lived long enough to document marrow engraftment. 21 rejected the graft and 19 of these died. 47 sustained engraftment and 18 of these died. In 16 patients, death was associated with graft versus host disease. 29 patients with sustained engraftment are alive with complete hematologic restoration between 8 mo and 5 yr. This analysis, by using a proportional hazards regression model, was directed at identifying factors that predicted survival (and absence of graft versus host disease). Of the 24 factors entered into the analysis only two strongly correlated with survival: (a) sex match of donor and recipient (P less than 0.01), and (b) absence of refractoriness to random donor platelets at the time of transplantation (P less than 0.05). Refractoriness adversely influenced the survival of the sex mismatched patients, These data suggest that X and Y-associated transplantation antigen systems are important determinants of the outcome of marrow grafts between HLA identical siblings for the treatment of aplastic anemia. The machanism by which refractoriness to random donor platelets influences survival is currently unclear.
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PMID:Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival. 1 72

Sixteen recipient-donor pairs who underwent unrelated BMT were analyzed for their HLA-class II identity by DNA-RFLP, in order to evaluate the importance of the genotypic HLA-DR, DQ, DP identity in the clinical outcome of unrelated bone marrow transplantation. From our study, a clear correlation between the HLA-DR, DQ, and DP genetic identity and acute GVHD (aGVHD) is not obvious since the number of studied cases is still limited. Nevertheless, it seems that the genetic identity influence the clinical outcome and patient survival. Six patients out of the ten who experienced severe aGVHD (greater than grade II) differed from their respective donors by HLA-DP mismatch in the GVH direction. Two patients rejected their grafts, and both presented HLA-DP incompatibilities in both GVH and HVG directions. Hence, HLA-DP may function as a transplantation antigen like the other HLA-class II molecules (DR, DQ) in unrelated BMT. Accordingly, we propose considering it in the pretransplantation histocompatibility testing. Nevertheless, further studies with larger numbers of cases should be done in order to confirm the role of HLA-DP. No correlation was observed between the mixed lymphocyte reaction (MLR) reactivity and the incidence of aGVHD. Accordingly, MLR response seems to be an incomplete indicator of GVHD, and a functional test is still to be found.
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PMID:HLA-DR, DQ, and/or DP genotypic mismatches between recipient-donor pairs in unrelated bone marrow transplantation and transplant clinical outcome. 197 52

Risk factors for post-transplant relapse were analysed retrospectively in 163 patients treated with allogenic bone marrow transplantation for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma in first to fourth remission or during relapse. Multifactorial analysis was performed according to Cox with fixed pretransplant covariates and post-transplant cytomegalovirus (CMV) infection and graft-versus-host (GVHD) as time-dependent covariates. Advanced stage of leukemia at the time of transplantation was an important risk factor for subsequent relapse. Furthermore, the study confirmed a graft-versus-leukaemia (GVL) activity associated with chronic GVHD, including de novo chronic GVHD (intensity factor 0.08, p = 0.004). In a model excluding chronic GVHD, female donor-to-male recipient (a risk factor for GVHD), was associated with decreased post-transplant relapse risk (intensity factor 0.3, p = 0.008), suggesting that an allo-reaction against a minor transplantation antigen (Hy) may mediate antileukaemic activity. A decrease of the relapse risk by a factor 0.18 was observed in recipients with AML as well as ALL when the donor was CMV seropositive (p = 0.0002). This effect was restricted to patients who had laboratory evidence of post-transplant CMV infection. When CMV infection occurred and donor was seropositive the relapse risk was reduced by a factor 0.035. The effect was not mediated through an increased occurrence of grade 2-4 acute or chronic GVHD and could not be explained by a statistical bias due to censoring of patients who died in remission. Rather, donor CMV immunity was associated with GVHD independent GVL activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Graft-versus-leukaemia activity associated with CMV-seropositive donor, post-transplant CMV infection, young donor age and chronic graft-versus-host disease in bone marrow allograft recipients. The Nordic Bone Marrow Transplantation Group. 164 52

CD1a, an antigen-presenting molecule related to major histocompatibility complex (MHC) class I, is frequently described as nonpolymorphic. In humans it is dimorphic, due to two linked amino acid substitutions in the alpha1 domain (Ile13Thr and Trp51Cys). The CD1a gene on chromosome 1 is not linked to MHC and may be mismatched between human leukocyte antigen-identical siblings. We analyzed 155 donor-recipient pairs of the Eurobank cohort, 141 matched for CD1a and 14 unmatched in the graft-versus-host disease (GVHD) direction. The burden of GVHD was not increased by CD1a mismatching. The incidence of GVHD in matched and unmatched groups was respectively: grade I-IV: 81% and 86% (P = 0.492); II-IV 61% and 57% (P = 0.495); III-IV 23% and 21% (P = 0.608). Adjusting for age, sex mismatch, GVHD prophylaxis, and conditioning did not reveal any significant difference. This suggests that, unlike conventional class I molecules, CD1a does not function as a transplantation antigen and does not require matching in hematopoietic stem cell transplantation.
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PMID:Impact of mismatching CD1a, a dimorphic antigen-presenting molecule, on graft-versus-host disease after hematopoietic stem cell transplantation. 1713 Jul 88

Hematopoietic cell transplantation (HCT) from an HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele-matched unrelated donor is a well-recognized life-saving treatment modality for patients with hematologic disorders. The morbidity and mortality from clinically significant acute graft-versus-host disease (aGVHD) remains a limitation. The extent to which transplantation outcome may be improved with donor matching for HLA-DP is not well defined. The risks of aGVHD, relapse, and mortality associated with HLA-DPB1 allele mismatching were determined in 5929 patients who received a myeloablative HCT from an HLA-A-, HLA-B-, HLA-C-, HLA-DRB1-, and HLA-DQB1-matched or -mismatched donor. There was a statistically significantly higher risk of both grades 2 to 4 aGVHD (odds ratio [OR] = 1.33; P < .001) and grades 3 to 4 aGVHD (OR = 1.26; P < .001) after HCT from an HLA-DPB1-mismatched donor compared with a matched donor. The increased risk of aGVHD was accompanied by a statistically significantly decrease in disease relapse (hazard ratio [HR] = 0.82; P = .01). HLA-DPB1 functions as a classical transplantation antigen. The increased risk of GVHD associated with HLA-DPB1 mismatching is accompanied by a lower risk of relapse. Knowledge of the DPB1 matching status prior to transplantation will aid in more precise risk stratification for the individual patient.
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PMID:The importance of HLA-DPB1 in unrelated donor hematopoietic cell transplantation. 1772 64

Allogeneic hematopoietic stem cell transplantation (HSCT) is an established curative therapy for a variety of hematologic malignancies. Genotypically HLA-identical sibling donors (ISDs)--who are available for about 30% of white patients are still considered as the best donors for HSCT. HLA-DPB1 is characterized by a high polymorphism, weak linkage disequilibrium with HLA-DR and -DQ loci, and its role as a transplantation antigen is controversial. We investigated the impact of HLA-DPB1 mismatch in HLA-identical sibling donor transplantation on a Graft-versus-host disease (GVHD). We Typed HLA-DPB1 by Innolipa in 33 patient-donor pairs with different hematologic diseases. Four (12.2 %) pairs with HLA-DPB1 mismatched were identified without identity. The incidence of grades II-IV aGVHD was higher in the HLA-DPB1 mismatched group (p=0.014, OR=26). Univariate analysis of risk factor for aGVHD II-IV showed that HLA-DPB1 is the only significant association (p=0.014), while non significant association was found between the age and sex of the patient, age of the donor, disease of the patient, and ABO compatibility, and positive CMV serology in patients and donors. It is concluded that HLA-DPB1 can mediate alloreactive responses and that HLA-DPB1 mismatch increases the risk of aGVHD in sibling donor stem cell transplantation.
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PMID:HLA-DPB1 mismatch and acute graft-versus host disease in HLA-identical sibling donors. 1797 7

The polymorphic products of major histocompatibility complex class I-related chain A (MICA) genes are important in solid organ transplantation rejection. MICA expression is limited to gut epithelium and may play a role in triggering acute graft-versus-host disease (aGVHD). A total of 236 recipients of unrelated donor transplantation were studied. Donor-recipient human leukocyte antigen (HLA) match was 10/10 human leukocyte antigen (HLA-A, -B, -C, -DRB1, -DQB1) in 73% and MICA mismatch in 8.4%. Because of physical vicinity of the loci, MICA mismatch was significantly associated with mismatch at HLA-B and HLA-C. A higher rate of grade II-IV aGVHD was seen in MICA-mismatched patients (80% vs 40%, P = .003) irrespective of degree of HLA matching (HLA 10/10 match: 75% vs 39%, P = .02) and HLA any mismatch (83% vs 46%, P = .003). The rate of grade II-IV gastrointestinal aGVHD was also higher in MICA-mismatched patients (35% vs 17%, P = .05). We conclude that MICA may represent novel a transplantation antigen recognized by human allogeneic T cells. This study was registered at ClinicalTrials.gov (Identifier NCT00506922).
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PMID:Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease. 1996 15

Clinical studies have indicated that HLA-DPB1 functions as a classical transplantation antigen in allogeneic stem cell transplantation. Mismatching for HLA-DPB1 was associated with an increased risk of graft-versus-host disease (GVHD), but also a decreased risk of disease relapse. However, specific HLA-DPB1 mismatches were associated with poor clinical outcome. It was suggested that this unfavorable effect was caused by a difference in immunogenicity between HLA-DPB1 alleles. To analyze whether immunogenicity of HLA-DPB1 mismatches could be predicted based on the presence or absence of specific amino acid sequences we developed a model to generate allo-HLA-DPB1 responses in vitro. We tested in total 48 different stimulator/responder combinations by stimulating CD4(+) T cells from 5 HLA-DPB1 homozygous individuals with the same antigen-presenting cells transduced with different allo-HLA-DPB1 molecules. HLA-DPB1 molecules used for stimulation comprised 76% to 99% of HLA-DPB1 molecules present in different ethnic populations. We show that all HLA-DPB1 mismatches as defined by allele typing resulted in high-frequency immune responses. Furthermore, we show that crossrecognition of different HLA-DPB1 molecules is a broadly observed phenomenon. We confirm previously described patterns in crossrecognition, and demonstrate that a high degree in similarity between HLA-DPB1 molecules is predictive for crossrecognition, but not for immunogenicity.
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PMID:HLA-DPB1 mismatching results in the generation of a full repertoire of HLA-DPB1-specific CD4+ T cell responses showing immunogenicity of all HLA-DPB1 alleles. 2035 Jun 10

Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice.
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PMID:Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD. 2754 7