PMID- 15480164
OWN - NLM
STAT- MEDLINE
DCOM- 20041103
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 78
IP  - 7
DP  - 2004 Oct 15
TI  - Human leukocyte antigen antibodies and human complement activation: role of IgG 
      subclass, specificity, and cytotoxic potential.
PG  - 995-1001
AB  - BACKGROUND: Human leukocyte antigen (HLA) antibodies are defined as complement 
      (C) fixing and clinically relevant based upon the complement-dependent 
      cytotoxicity (CDC) test. However, the sub-lytic activation of individual C 
      components is of critical biologic significance. The requirements of HLA 
      antibodies to activate human C are not known. METHODS: IgG, IgM, IgG subclasses, 
      and human C3b deposition upon T cells were evaluated by flow cytometry with sera 
      from HLA-sensitized patients and human monoclonal HLA antibodies. RESULTS: 
      Comparative studies showed that there was poor correlation between the amount of 
      IgG on target cells and their ability to produce CDC. Human C3b deposition was 
      influenced more by the particular serum/cell combination under study than by the 
      amount of IgG, with some combinations showing high IgG and low C3b and others 
      showing low IgG and high C3b. IgG1 was the predominant IgG subclass in all 
      patients. The other subclasses were low or undetectable and did not correlate 
      with C3b deposition. Human monoclonal HLA antibodies, mostly IgG1, did not 
      activate human C efficiently despite high IgG binding. However, combinations of 
      two monoclonal antibodies to different epitopes of the same antigen did produce 
      significant C3b deposition. CONCLUSIONS: Contrary to common assumptions, CDC, IgG 
      binding, and IgG subclass are poor predictors of human C activation by HLA 
      antibodies. The mix of specificities in a given serum and the antigens of a 
      particular target cell appear to determine the efficiency of C activation. 
      Measuring both antibody and C3b deposition (or other C component) may improve the 
      assessment of donor-recipient compatibility.
FAU - Kushihata, Fumiki
AU  - Kushihata F
AD  - Department of Pathology, University of Florida College of Medicine, Gainesville, 
      FL 32608, USA.
FAU - Watanabe, Jota
AU  - Watanabe J
FAU - Mulder, Arend
AU  - Mulder A
FAU - Claas, Frans
AU  - Claas F
FAU - Scornik, Juan C
AU  - Scornik JC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Complement C3)
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Isoantibodies)
RN  - 80295-43-8 (Complement C3b)
SB  - IM
MH  - Antibodies, Monoclonal/immunology
MH  - *Antibody Specificity
MH  - *Complement Activation
MH  - Complement C3/metabolism
MH  - Complement C3b/metabolism
MH  - *Cytotoxicity, Immunologic
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Immunoglobulin G/classification/*physiology
MH  - Isoantibodies/*physiology
EDAT- 2004/10/14 09:00
MHDA- 2004/11/04 09:00
CRDT- 2004/10/14 09:00
PHST- 2004/10/14 09:00 [pubmed]
PHST- 2004/11/04 09:00 [medline]
PHST- 2004/10/14 09:00 [entrez]
AID - 00007890-200410150-00007 [pii]
AID - 10.1097/01.tp.0000136966.63957.e2 [doi]
PST - ppublish
SO  - Transplantation. 2004 Oct 15;78(7):995-1001. doi: 
      10.1097/01.tp.0000136966.63957.e2.