PMID- 15935890
OWN - NLM
STAT- MEDLINE
DCOM- 20051212
LR  - 20061115
IS  - 0198-8859 (Print)
IS  - 0198-8859 (Linking)
VI  - 66
IP  - 5
DP  - 2005 May
TI  - [C4d]FlowPRA screening--a specific assay for selective detection of 
      complement-activating anti-HLA alloantibodies.
PG  - 526-34
AB  - On waiting lists, transplant candidates are routinely screened for potentially 
      harmful complement-fixing alloantibodies using complement-dependent cytotoxicity 
      (CDC) panel-reactive antibody (PRA) testing. We have recently developed a novel 
      cell-independent assay for assessment of complement-activating panel reactivity 
      ([C4d]FlowPRA), which is based on selective flow-cytometric detection of 
      alloantibody-triggered C4 complement split product deposition to human leukocyte 
      antigen (HLA)-coated FlowPRA beads. Serum specimens selected from 120 transplant 
      candidates were evaluated by [C4d]FlowPRA (HLA class I vs II) in comparison with 
      FlowPRA IgG alloantibody screening (HLA class I vs II), a method detecting both 
      complement- and noncomplement-activating alloantibodies, and with CDC-PRA on 
      separated T (T-CDC) or B cells (B-CDC, evaluation on platelet-absorbed sera). For 
      each assay, >/=10% PRA reactivity was considered positive. Comparing 
      complement-dependent PRA assays with standard FlowPRA, the specificity calculated 
      for [C4d]FlowPRA (HLA class I: 92%; class II: 100%) was found to be superior to 
      that of CDC testing (T-CDC-PRA: 79%; B-CDC-PRA: 86%). Because 
      noncomplement-activating alloreactivities were not detected for both techniques, 
      low sensitivities were calculated ([C4d]FlowPRA HLA class I: 61%; class II: 31%; 
      T-CDC-PRA: 70%; B-CDC-PRA: 55%). Compared with CDC-PRA, [C4d]FlowPRA gave a high 
      specificity (HLA class I compared with T-CDC: 89%, HLA class II compared with 
      B-CDC: 95%) but, at least in part because of false-positive CDC results, a modest 
      sensitivity (66% and 38%, respectively). For both HLA classes, we found a highly 
      significant association between absolute [C4d]FlowPRA and CDC-PRA levels (p < 
      0.0001). Our results suggest that detection of C4 split product deposition to 
      FlowPRA beads may represent an attractive HLA-specific and time-effective 
      alternative to CDC-PRA screening.
FAU - Wahrmann, Markus
AU  - Wahrmann M
AD  - Department of Medicine III, Medical University of Vienna, Vienna, Austria.
FAU - Exner, Markus
AU  - Exner M
FAU - Haidbauer, Bettina
AU  - Haidbauer B
FAU - Schillinger, Martin
AU  - Schillinger M
FAU - Regele, Heinz
AU  - Regele H
FAU - Kormoczi, Gunther
AU  - Kormoczi G
FAU - Bohmig, Georg A
AU  - Bohmig GA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20050212
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Complement C4)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - B-Lymphocytes/immunology
MH  - Complement Activation/*immunology
MH  - Complement C4/*immunology/metabolism
MH  - Cytotoxicity Tests, Immunologic
MH  - Flow Cytometry/methods
MH  - HLA Antigens/*immunology
MH  - Histocompatibility Antigens Class I/immunology
MH  - Histocompatibility Antigens Class II/immunology
MH  - Humans
MH  - Immunoassay/methods
MH  - Isoantibodies/*immunology
MH  - Leukocytes, Mononuclear/immunology
MH  - Microspheres
MH  - Reproducibility of Results
MH  - T-Lymphocytes/immunology
EDAT- 2005/06/07 09:00
MHDA- 2005/12/15 09:00
CRDT- 2005/06/07 09:00
PHST- 2004/09/09 00:00 [received]
PHST- 2004/12/21 00:00 [revised]
PHST- 2004/12/31 00:00 [accepted]
PHST- 2005/06/07 09:00 [pubmed]
PHST- 2005/12/15 09:00 [medline]
PHST- 2005/06/07 09:00 [entrez]
AID - S0198-8859(05)00014-5 [pii]
AID - 10.1016/j.humimm.2004.12.007 [doi]
PST - ppublish
SO  - Hum Immunol. 2005 May;66(5):526-34. doi: 10.1016/j.humimm.2004.12.007. Epub 2005 
      Feb 12.