BACKGROUND: The presence of preformed alloantibodies with the ability to activate complement may pose a particular risk for kidney allograft rejection. The aim of this study was to evaluate variables that determine the complement-fixing capability of human leukocyte antigen (HLA) sensitization. METHODS: Sixty-five sensitized patients with > or =10% pretransplant panel-reactive antibody (PRA) levels uncovered by immunoglobulin G [IgG]FlowPRA HLA class I and/or class II screening were included. Applying modified FlowPRA screening, sera were evaluated for patterns of alloreactive IgG subclasses and IgM, and, in parallel, for their complement-activating ability assessed by flow cytometric detection of human complement split product deposition ([C4d]FlowPRA). RESULTS: Approximately two-thirds (68%) of tested sera were found to contain complement-fixing alloreactivity (> or =10%[C4d]FlowPRA). IgG1 type panel reactivity was predominant (detectable HLA class I and II reactivity in 93% and 91% of IgG-positive sera), followed by IgG3 (49%/44%), IgG2 (44%/27%), and IgG4 (19%/11%). Applying partial correlation we found an independent correlation of both %[IgG1]FlowPRA and %[IgG3]FlowPRA with %[C4d]FlowPRA reactivities (P< or =0.01). In addition, for IgG1 a contribution of the amount of bound alloantibody to complement-fixation was observed. Complement-fixation was also favored by the simultaneous presence of alloreactive IgG1, IgG3, and IgM. Previous grafting, but not pregnancy and transfusion, was independently associated with complement-fixing sensitization (P<0.05), presumably due to increased IgG1 type reactivity. CONCLUSIONS: Anti-HLA antibody-triggered complement activation is dependent on both the pattern of Ig reactivities and the amount of bound antibody. Previous transplantation represents a major risk factor for the development of complement-fixing sensitization.
BACKGROUND: The presence of preformed alloantibodies with the ability to activate complement may pose a particular risk for kidney allograft rejection. The aim of this study was to evaluate variables that determine the complement-fixing capability of human leukocyte antigen (HLA) sensitization. METHODS: Sixty-five sensitized patients with > or =10% pretransplant panel-reactive antibody (PRA) levels uncovered by immunoglobulin G [IgG]FlowPRA HLA class I and/or class II screening were included. Applying modified FlowPRA screening, sera were evaluated for patterns of alloreactive IgG subclasses and IgM, and, in parallel, for their complement-activating ability assessed by flow cytometric detection of human complement split product deposition ([C4d]FlowPRA). RESULTS: Approximately two-thirds (68%) of tested sera were found to contain complement-fixing alloreactivity (> or =10%[C4d]FlowPRA). IgG1 type panel reactivity was predominant (detectable HLA class I and II reactivity in 93% and 91% of IgG-positive sera), followed by IgG3 (49%/44%), IgG2 (44%/27%), and IgG4 (19%/11%). Applying partial correlation we found an independent correlation of both %[IgG1]FlowPRA and %[IgG3]FlowPRA with %[C4d]FlowPRA reactivities (P< or =0.01). In addition, for IgG1 a contribution of the amount of bound alloantibody to complement-fixation was observed. Complement-fixation was also favored by the simultaneous presence of alloreactive IgG1, IgG3, and IgM. Previous grafting, but not pregnancy and transfusion, was independently associated with complement-fixing sensitization (P<0.05), presumably due to increased IgG1 type reactivity. CONCLUSIONS: Anti-HLA antibody-triggered complement activation is dependent on both the pattern of Ig reactivities and the amount of bound antibody. Previous transplantation represents a major risk factor for the development of complement-fixing sensitization.
Authors: JoonHo Lee; Roberto Romero; Yi Xu; Jung-Sun Kim; Ji Young Park; Juan Pedro Kusanovic; Tinnakorn Chaiworapongsa; Sonia S Hassan; Chong Jai Kim Journal: Am J Reprod Immunol Date: 2011-09-27 Impact factor: 3.886
Authors: Joonho Lee; Roberto Romero; Tinnakorn Chaiworapongsa; Zhong Dong; Adi L Tarca; Yi Xu; Po Jen Chiang; Juan Pedro Kusanovic; Sonia S Hassan; Lami Yeo; Bo Hyun Yoon; Nandor Gabor Than; Chong Jai Kim Journal: Am J Reprod Immunol Date: 2013-07-30 Impact factor: 3.886
Authors: JoonHo Lee; Roberto Romero; Yi Xu; Jezid Miranda; Wonsuk Yoo; Piya Chaemsaithong; Juan Pedro Kusanovic; Tinnakorn Chaiworapongsa; Adi L Tarca; Steven J Korzeniewski; Sonia S Hassan; Nandor Gabor Than; Bo Hyun Yoon; Chong Jai Kim Journal: Am J Reprod Immunol Date: 2013-08 Impact factor: 3.886