Protein microarrays identify antibodies to protein kinase Czeta that are associated with a greater risk of allograft loss in pediatric renal transplant recipients. Export

@article{citeulike:5927943, abstract = {Antibodies to human leukocyte antigens (HLAs) are a risk factor for acute renal allograft rejection and loss. The role of non-HLAs and their significance to allograft rejection have gained recent attention. Here, we applied protein microarray technology, with the capacity to simultaneously identify 5056 potential antigen targets, to assess non-HLA antibody formation in 15 pediatric renal transplant recipients during allograft rejection. Comparison of the pre- and post-transplant serum identified de novo antibodies to 229 non-HLA targets, 36 of which were present in multiple patients at allograft rejection. On the basis of its reactivity, protein kinase Czeta (PKCzeta) was selected for confirmatory testing and clinical study. Immunohistochemical analysis found PKCzeta both within the renal tissue and infiltrating lymphocytes at rejection. Patients who had an elevated anti-PKCzeta titer developed rejection, which was significantly more likely to result in graft loss. The absence of C4d deposition in patients with high anti-PKCzeta titers suggests that it is a marker of severe allograft injury rather than itself being pathogenic. Presumably, critical renal injury and inflammation associated with this rejection subtype lead to the immunological exposure of PKCzeta with resultant antibody formation. Prospective assessment of serum anti-PKCzeta levels at allograft rejection will be needed to confirm these results.Kidney International advance online publication, 7 October 2009; doi:10.1038/ki.2009.384.}, author = {Sutherland, Scott M. and Li, Li and Sigdel, Tara K. and Wadia, Persis P. and Miklos, David B. and Butte, Atul J. and Sarwal, Minnie M.}, citeulike-article-id = {5927943}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ki.2009.384}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19812540}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19812540}, day = {7}, doi = {10.1038/ki.2009.384}, issn = {1523-1755}, journal = {Kidney international}, keywords = {allograft\_rejection, antibodies, antibody\_formation, antigen, protein\_microarray\_technology, renal\_transplant\_recipients, titer}, month = {October}, posted-at = {2009-10-12 17:29:42}, priority = {3}, title = {Protein microarrays identify antibodies to protein kinase Czeta that are associated with a greater risk of allograft loss in pediatric renal transplant recipients.}, url = {http://dx.doi.org/10.1038/ki.2009.384}, year = {2009} }

TY - JOUR ID - citeulike:5927943 L3 - citeulike-article-id:5927943 N2 - Antibodies to human leukocyte antigens (HLAs) are a risk factor for acute renal allograft rejection and loss. The role of non-HLAs and their significance to allograft rejection have gained recent attention. Here, we applied protein microarray technology, with the capacity to simultaneously identify 5056 potential antigen targets, to assess non-HLA antibody formation in 15 pediatric renal transplant recipients during allograft rejection. Comparison of the pre- and post-transplant serum identified de novo antibodies to 229 non-HLA targets, 36 of which were present in multiple patients at allograft rejection. On the basis of its reactivity, protein kinase Czeta (PKCzeta) was selected for confirmatory testing and clinical study. Immunohistochemical analysis found PKCzeta both within the renal tissue and infiltrating lymphocytes at rejection. Patients who had an elevated anti-PKCzeta titer developed rejection, which was significantly more likely to result in graft loss. The absence of C4d deposition in patients with high anti-PKCzeta titers suggests that it is a marker of severe allograft injury rather than itself being pathogenic. Presumably, critical renal injury and inflammation associated with this rejection subtype lead to the immunological exposure of PKCzeta with resultant antibody formation. Prospective assessment of serum anti-PKCzeta levels at allograft rejection will be needed to confirm these results.Kidney International advance online publication, 7 October 2009; doi:10.1038/ki.2009.384. JF - Kidney international SN - 1523-1755 TI - Protein microarrays identify antibodies to protein kinase Czeta that are associated with a greater risk of allograft loss in pediatric renal transplant recipients. KW - allograft_rejection KW - antibodies KW - antibody_formation KW - antigen KW - protein_microarray_technology KW - renal_transplant_recipients KW - titer AU - Sutherland, Scott AU - Li, Li AU - Sigdel, Tara AU - Wadia, Persis AU - Miklos, David AU - Butte, Atul AU - Sarwal, Minnie PY - 2009/10/07/ UR - http://dx.doi.org/10.1038/ki.2009.384 ER -