PMID- 21637140
OWN - NLM
STAT- MEDLINE
DCOM- 20110824
LR  - 20110621
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 92
IP  - 1
DP  - 2011 Jul 15
TI  - Pretransplant IgG subclasses of donor-specific human leukocyte antigen antibodies 
      and development of antibody-mediated rejection.
PG  - 41-7
LID - 10.1097/TP.0b013e31821cdf0d [doi]
AB  - BACKGROUND: The subclass of IgG antibodies contributes to their capability to 
      activate complement. It is currently unknown whether the pretransplant IgG 
      subclass composition allows distinguishing harmful from presumably irrelevant 
      donor-specific human leukocyte antigen (HLA) antibodies (HLA-DSA) detected by 
      single-antigen flow beads (SAFB). METHODS: Seventy-four patients transplanted in 
      the presence of HLA-DSA were investigated. HLA-DSA characteristics were not 
      different between patients experiencing antibody-mediated rejection (AMR) (n=40) 
      and patients who did not (n=34) experience AMR. Sera were reanalyzed using SAFB 
      with IgG subclass-specific reporter antibodies. RESULTS: The 74 patients had in 
      total 141 HLA-DSA. IgG1 was the predominant subclass (78%), followed by IgG2 
      (49%), IgG3 (36%), and IgG4 (20%). When grouped according to the 
      complement-activating capability, only 4 of 74 patients (5%) had exclusively 
      weak/no complement-activating HLA-DSA (i.e., IgG2 and IgG4), 21 of 74 patients 
      (28%) had isolated strong complement-activating HLA-DSA (i.e., IgG1 and IgG3), 
      and 46 of 74 patients (62%) had a mixture of both. There was no difference 
      between the strong complement-activating and the mixture group regarding 
      incidence of AMR (57% vs. 54%; P=0.81), phenotypes of AMR (P=0.70), and 
      death-censored allograft survival at 5 years (78% vs. 78%; P=0.74). 
      Interestingly, patients with exclusively weak/no complement-activating HLA-DSA 
      (n=4) had a numerically lower incidence of AMR (25%) and no allograft loss has 
      occurred yet. CONCLUSION: In 90% of patients, pretransplant HLA-DSA are composed 
      of isolated strong or a mixture of strong and weak/no complement-activating IgG 
      subclasses. Because outcomes in these two groups were similar, pretransplant IgG 
      subclass analysis is likely not providing substantial value beyond the standard 
      IgG SAFB assay for pretransplant risk stratification.
FAU - Honger, Gideon
AU  - Honger G
AD  - Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, 
      Basel, Switzerland.
FAU - Hopfer, Helmut
AU  - Hopfer H
FAU - Arnold, Marie-Luise
AU  - Arnold ML
FAU - Spriewald, Bernd M
AU  - Spriewald BM
FAU - Schaub, Stefan
AU  - Schaub S
FAU - Amico, Patrizia
AU  - Amico P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (HLA Antigens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Isoantibodies)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Complement Activation
MH  - Female
MH  - Graft Rejection/*etiology/*immunology
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Immunoassay
MH  - Immunoglobulin G/blood/*classification
MH  - Isoantibodies/blood/*classification
MH  - Kidney Transplantation/*adverse effects/*immunology
MH  - Male
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Risk Factors
MH  - *Tissue Donors
MH  - Young Adult
EDAT- 2011/06/04 06:00
MHDA- 2011/08/25 06:00
CRDT- 2011/06/04 06:00
PHST- 2011/06/04 06:00 [entrez]
PHST- 2011/06/04 06:00 [pubmed]
PHST- 2011/08/25 06:00 [medline]
AID - 10.1097/TP.0b013e31821cdf0d [doi]
PST - ppublish
SO  - Transplantation. 2011 Jul 15;92(1):41-7. doi: 10.1097/TP.0b013e31821cdf0d.