PMID- 17414705
OWN - NLM
STAT- MEDLINE
DCOM- 20070508
LR  - 20070406
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 83
IP  - 6
DP  - 2007 Mar 27
TI  - Determinants of the complement-fixing ability of recipient presensitization 
      against HLA antigens.
PG  - 727-33
AB  - 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.
FAU - Bartel, Gregor
AU  - Bartel G
AD  - Department of Medicine III, Medical University of Vienna, Vienna, Austria.
FAU - Wahrmann, Markus
AU  - Wahrmann M
FAU - Exner, Markus
AU  - Exner M
FAU - Regele, Heinz
AU  - Regele H
FAU - Schillinger, Martin
AU  - Schillinger M
FAU - Horl, Walter H
AU  - Horl WH
FAU - Bohmig, Georg A
AU  - Bohmig GA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Isoantibodies)
RN  - 9007-36-7 (Complement System Proteins)
SB  - IM
MH  - Adult
MH  - Antigen-Antibody Complex/*immunology
MH  - Complement Activation/physiology
MH  - Complement Fixation Tests/methods
MH  - Complement System Proteins/immunology/*physiology
MH  - Female
MH  - Graft Rejection/immunology
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Immunoglobulin G/immunology
MH  - Immunoglobulin M/immunology
MH  - Isoantibodies/*immunology
MH  - Kidney Transplantation/*immunology
MH  - Male
MH  - Middle Aged
MH  - Risk Factors
EDAT- 2007/04/07 09:00
MHDA- 2007/05/09 09:00
CRDT- 2007/04/07 09:00
PHST- 2007/04/07 09:00 [pubmed]
PHST- 2007/05/09 09:00 [medline]
PHST- 2007/04/07 09:00 [entrez]
AID - 00007890-200703270-00013 [pii]
AID - 10.1097/01.tp.0000256337.18347.aa [doi]
PST - ppublish
SO  - Transplantation. 2007 Mar 27;83(6):727-33. doi: 
      10.1097/01.tp.0000256337.18347.aa.