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Isabel Quiroga

Publications and source records attributed to Isabel Quiroga.

5 recordsLinked to original sources
PubMed2006

Replication of the association of HLA-B7 with Alzheimer's disease: a role for homozygosity?

BACKGROUND: There are reasons to expect an association with Alzheimer's disease (AD) within the HLA region. The HLA-B & C genes have, however, been relatively understudied. A geographically specific association with HLA-B7 & HLA-Cw*0702 had been suggested by our previous, small study. METHODS: We studied the HLA-B & C alleles in 196 cases of 'definite' or 'probable' AD and 199 elderly controls of the OPTIMA cohort, the largest full study of these alleles in AD to date. RESULTS: We replicated the association of HLA-B7 with AD (overall, adjusted odds ratio = 2.3, 95% confidence interval = 1.4-3.7, p = 0.001), but not the previously suggested interaction with the epsilon4 allele of apolipoprotein E. Results for HLA-Cw*0702, which is in tight linkage disequilibrium with HLA-B7, were consistent with those for the latter. Homozygotes of both alleles appeared to be at particularly high risk of AD. CONCLUSION: HLA-B7 and HLA-Cw*0702 are associated with AD in the Oxford population. Because of the contradictions between cohorts in our previous study, we suggest that these results may be geographically specific. This might be because of differences between populations in the structure of linkage disequilibrium or in interactions with environmental, genetic or epigenetic factors. A much larger study will be needed to clarify the role of homozygosity of HLA alleles in AD risk.

Journal Article↗
PubMed2006

Expression of MHC class I-related Chain B (MICB) molecules on renal transplant biopsies.

BACKGROUND: MICA and MICB (MHC class I-related chain A and B) are polymorphic genes that encode molecules related to MHC class I and are expressed on epithelial cells in response to stress. Incompatible donor MIC antigens can stimulate antibody production in transplant recipients. This study was designed to determine MICB expression in kidney pretransplant and any subsequent changes in expression following transplantation and to correlate changes with inflammatory markers and clinical events. METHODS: Paired renal biopsies obtained from living donor (n=10) and cadaveric allografts (n=50) before and 7 days posttransplant were stained for MICB, leukocytic infiltration, and HLA class II antigens. RESULTS: Variable tubular MICB expression was evident in donor biopsies [high 6/60 (10%), low/negative 13/60 (22%), intermediate 41/60 (68%)]. Following transplantation, MICB was up-regulated on renal tubules of 17/60 (28%) biopsies and was associated with MHC class II antigen induction (P=0.02) and leukocyte infiltration (P=0.01). Acute tubular necrosis leading to delayed graft function (DGF) and acute rejection (AR) cause cellular stress within the transplanted kidney. We found a strong association between up-regulation of MICB and cellular stress, 15/17 biopsies with up-regulated MICB expression had AR and/or DGF (P=0.003). CONCLUSIONS: This is the first study demonstrating variable levels of MICB expression in kidneys before transplantation and induction of MICB expression following renal transplantation. MICB expression is associated with HLA class II antigen induction, leukocytic infiltration of the graft and cellular stress in the transplanted kidney. Expression of MICB could contribute significantly to the alloimmune response in mismatched donors and recipients.

Adult↗
PubMed2006

Major effects of delayed graft function and cold ischaemia time on renal allograft survival.

BACKGROUND: There is mounting evidence from experimental and clinical studies that the quality of organs from cadaver donors may be influenced by events occurring around the time of brain death, and that these may affect transplant outcome. The aim of this study is to investigate the influence of donor factors on renal allograft outcome in a homogeneous cohort of 518 patients transplanted in a single centre over a 9 year period. METHODS: Endpoints of the study were delayed graft function (DGF), acute rejection (AR), 1 year graft survival and long-term survival of those grafts that reached 1 year. Multivariate analysis was performed to determine factors that may have influenced the graft outcome indicators. RESULTS: DGF was the major predictor of graft failure overall with cold ischaemia time (CIT) as an important independent factor. The level of histocompatibility did not influence graft survival. DGF was the major factor affecting 1 year graft survival (P<0.0005) with effects persisting beyond 1 year. DGF was significantly influenced by CIT, donor age, female kidney into male recipient and donor creatinine (P<0.05). Other donor factors and factors associated with donor management were not risk factors for DGF, rejection episodes or graft survival. The risk factors for a number of AR episodes were HLA-DR mismatch and DGF (P<0.005). When grafts surviving for 1 year were considered, only CIT, recipient age and creatinine at 1 year (P<0.05) were found to affect graft survival significantly. CONCLUSIONS: The results of this analysis of well-matched transplant recipients show that CIT and DGF are the most important predictors of poor short and long-term graft survival. Therefore, in order to improve the long-term survival of renal allografts efforts should focus on limiting CIT and the damage that occurs during this period and on improving our understanding of DGF.

Adult↗
PubMed2004

C4d deposition in early renal allograft protocol biopsies.

BACKGROUND: Deposition of the complement protein C4d in renal allograft biopsies obtained during graft dysfunction and rejection has been proposed to be a sensitive marker of antibody-mediated acute rejection. To determine the diagnostic specificity of C4d deposition, it is important to study biopsies from allografts with no evidence of dysfunction. In this study, we examined C4d deposition in protocol biopsies obtained irrespective of clinical status. METHODS: Immunohistochemistry for C4d was performed on routine protocol biopsies preimplantation and on day 7 posttransplantation from 48 unselected renal allografts. Serum samples obtained up to 1 month after transplantation were assayed for donor-reactive antibodies (DRA). Results were correlated with histopathology and clinical outcome measures. RESULTS: Diffuse C4d deposition was detected in the peritubular capillaries of 6 of 48 (13%) biopsies. C4d deposition was present in 5 of 15 (33%) biopsies that showed acute rejection (Banff 97, category 4) but only in 1 of 33 (3%) biopsies with no rejection (P=0.003, 97% specificity). Posttransplant DRAs were detected in 21 of 48 (44%) patients. All five recipients with C4d deposition and rejection had posttransplant DRA; the recipient whose biopsy showed C4d positivity, but not rejection, did not have detectable DRA. C4d deposition was not treated with plasmapheresis or intravenous immunoglobulin and was not associated with poor posttransplant graft outcome at 1-year follow-up. CONCLUSIONS: Our results show that in early posttransplant protocol biopsies, C4d is a specific marker for the presence of humoral rejection, as indicated by its association with DRA and acute histologic rejection.

Adult↗