PMID- 20395886
OWN - NLM
STAT- MEDLINE
DCOM- 20100713
LR  - 20220311
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 89
IP  - 12
DP  - 2010 Jun 27
TI  - C4d-fixing capability of low-level donor-specific HLA antibodies is not 
      predictive for early antibody-mediated rejection.
PG  - 1471-5
LID - 10.1097/TP.0b013e3181dc13e7 [doi]
AB  - BACKGROUND: Recent studies indicate that not all low-level donor-specific human 
      leukocyte antigen (HLA) antibodies (HLA-DSA) (i.e., positive by solid-phase 
      assays, negative by complement-dependent cytotoxic-crossmatch) have a detrimental 
      clinical impact. The aim of this study was to investigate whether the 
      pretransplant C4d-fixing capability allows distinguishing harmful from presumably 
      clinically irrelevant HLA-DSA. METHODS: We retrospectively investigated 64 
      patients with low-level HLA-DSA detected by single-antigen flow beads (SAFB). 
      Thirty-four of 64 patients (53%) experienced early antibody-mediated rejection 
      (AMR), whereas 30 patients (47%) did not. HLA-DSA characteristics (i.e., number, 
      class, and strength), frequency of retransplants, and immunosuppressive regimens 
      were not different in these two groups. Pretransplant sera were reanalyzed using 
      a modified SAFB assay measuring C4d fixation induced by HLA antibodies. RESULTS: 
      C4d-fixing HLA-DSA were observed in 11 of 64 patients (17%). AMR occurred in 6 of 
      11 patients (55%) with C4d-fixing HLA-DSA and in 28 of 53 patients (53%) without 
      C4d-fixing HLA-DSA (P=1.0). Positive C4d staining in peritubular capillaries was 
      detected in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 21 of 53 
      patients (40%) without C4d-fixing HLA-DSA (P=0.50). CONCLUSION: The pretransplant 
      capability of low-level HLA-DSA to trigger C4d fixation in vitro is not 
      predictive for early AMR or C4d deposition in peritubular capillaries in vivo. 
      This argues against pretransplant C4d SAFB testing to define the clinical 
      relevance of low-level HLA-DSA.
FAU - Honger, Gideon
AU  - Honger G
AD  - Transplantation Immunology and Nephrology, University Hospital Basel, Basel, 
      Switzerland.
FAU - Wahrmann, Markus
AU  - Wahrmann M
FAU - Amico, Patrizia
AU  - Amico P
FAU - Hopfer, Helmut
AU  - Hopfer H
FAU - Bohmig, Georg A
AU  - Bohmig GA
FAU - Schaub, Stefan
AU  - Schaub S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Antibodies)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Peptide Fragments)
RN  - 80295-50-7 (Complement C4b)
RN  - 80295-52-9 (complement C4d)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies/*chemistry
MH  - Biopsy
MH  - Capillaries/immunology
MH  - Complement C4b/chemistry
MH  - Female
MH  - Graft Rejection
MH  - HLA Antigens/*chemistry
MH  - Humans
MH  - Immunoglobulin G/chemistry
MH  - Kidney Transplantation/*methods
MH  - Male
MH  - Middle Aged
MH  - Peptide Fragments/chemistry
MH  - Retrospective Studies
EDAT- 2010/04/17 06:00
MHDA- 2010/07/14 06:00
CRDT- 2010/04/17 06:00
PHST- 2010/04/17 06:00 [entrez]
PHST- 2010/04/17 06:00 [pubmed]
PHST- 2010/07/14 06:00 [medline]
AID - 10.1097/TP.0b013e3181dc13e7 [doi]
PST - ppublish
SO  - Transplantation. 2010 Jun 27;89(12):1471-5. doi: 10.1097/TP.0b013e3181dc13e7.