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Abstracts / Human Immunology 74 (2013) 1–49
DONOR SPECIFIC ANTIBODY IS A PREDICTOR OF DE-NOVO AUTOIMMUNE HEPATITIS FOLLOWING PEDIATRIC LIVER TRANSPLANTATION. Michelle J. Hickey 1, Laura J. Wozniak 2, Tiffany Smith 1, Gertrudes Aguas 1, Giovanni Lopez 1, Yael Korin 1, Robert S. Venick 2, Sue V. McDiarmid 2, Elaine F. Reed 1. 1 Department of Pathology and Laboratory Medicine, Immunogenetics Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2 Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Aim: The role of donor-specific HLA antibodies (DSA) following liver transplantation (LTx) is not clearly established. Our aim was to assess the presence of DSA in pediatric LTx recipients. We hypothesized that DSA would be detected (+DSA) in patients with late allograft dysfunction due to de-novo autoimmune hepatitis (d-AIH). Methods: Serum was collected at routine clinic visits from 50 pediatric LTx recipients a mean of 11.8 ± 5.3 years post LTx, and classified into four clinical phenotypes: non-tolerant with biopsy-proven late acute cellular rejection (n = 6) and/or d-AIH (n = 12); stable with normal liver function on maintenance tacrolimus (n = 25); tolerant with normal liver function off immunosuppression P2 years (n = 7). Samples were blinded and antibody detection was performed using LABScreen HLA Class I and II Single Antigen beads (One Lambda) and Luminex multiplex technology. Descriptive statistics and multivariate logistic regression were performed with results reported as means and odds ratios (OR). Results: HLA antibodies were detected in 28/50 (56%) of patients, with the majority of DSA directed against HLA Class II DR or DQ loci (40% and 52%, respectively). Patients with +DSA had a mean of 1.8 (range 1-4) DSA with a mean MFI of 11681 ± 8227. Patients with +DSA were younger at LTx (2.4 ± 2.9 vs 5.4 ± 5.4 years, p = 0.01). There were no differences in other clinical variables including sex, primary diagnosis, history of re-LTx, and early acute rejection. Age in years at LTx (OR 0.5, p = 0.01), history of post transplant lymphoproliferative disorder (OR 0.1, p = 0.01) and late rejection (OR 27, p = 0.02) are the strongest predictors of +DSA. Patients with d-AIH tended to be +DSA (10/12 patients, p = 0.05), a trend that was not observed in the other phenotypes. +DSA is the strongest multivariate predictor of d-AIH (OR 19, p = 0.03). Conclusions: DSA are common after pediatric LTx and detected more frequently in patients with d-AIH, suggesting d-AIH may be a form of antibody-mediated rejection.
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Abstracts / Human Immunology 74 (2013) 1–49
DONOR SPECIFIC ANTIBODY IS A PREDICTOR OF DE-NOVO AUTOIMMUNE HEPATITIS FOLLOWING PEDIATRIC LIVER TRANSPLANTATION. Michelle J. Hickey 1, Laura J. Wozniak 2, Tiffany Smith 1, Gertrudes Aguas 1, Giovanni Lopez 1, Yael Korin 1, Robert S. Venick 2, Sue V. McDiarmid 2, Elaine F. Reed 1. 1 Department of Pathology and Laboratory Medicine, Immunogenetics Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2 Pediatric Gastroenterology, Hepatology, and Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Aim: The role of donor-specific HLA antibodies (DSA) following liver transplantation (LTx) is not clearly established. Our aim was to assess the presence of DSA in pediatric LTx recipients. We hypothesized that DSA would be detected (+DSA) in patients with late allograft dysfunction due to de-novo autoimmune hepatitis (d-AIH). Methods: Serum was collected at routine clinic visits from 50 pediatric LTx recipients a mean of 11.8 ± 5.3 years post LTx, and classified into four clinical phenotypes: non-tolerant with biopsy-proven late acute cellular rejection (n = 6) and/or d-AIH (n = 12); stable with normal liver function on maintenance tacrolimus (n = 25); tolerant with normal liver function off immunosuppression P2 years (n = 7). Samples were blinded and antibody detection was performed using LABScreen HLA Class I and II Single Antigen beads (One Lambda) and Luminex multiplex technology. Descriptive statistics and multivariate logistic regression were performed with results reported as means and odds ratios (OR). Results: HLA antibodies were detected in 28/50 (56%) of patients, with the majority of DSA directed against HLA Class II DR or DQ loci (40% and 52%, respectively). Patients with +DSA had a mean of 1.8 (range 1-4) DSA with a mean MFI of 11681 ± 8227. Patients with +DSA were younger at LTx (2.4 ± 2.9 vs 5.4 ± 5.4 years, p = 0.01). There were no differences in other clinical variables including sex, primary diagnosis, history of re-LTx, and early acute rejection. Age in years at LTx (OR 0.5, p = 0.01), history of post transplant lymphoproliferative disorder (OR 0.1, p = 0.01) and late rejection (OR 27, p = 0.02) are the strongest predictors of +DSA. Patients with d-AIH tended to be +DSA (10/12 patients, p = 0.05), a trend that was not observed in the other phenotypes. +DSA is the strongest multivariate predictor of d-AIH (OR 19, p = 0.03). Conclusions: DSA are common after pediatric LTx and detected more frequently in patients with d-AIH, suggesting d-AIH may be a form of antibody-mediated rejection.