Antibody testing for cardiac antibody-mediated rejection: which panel correlates best with cardiovascular death?
BACKGROUND
Recent efforts are being undertaken to update and refine current diagnostic criteria for antibody-mediated rejection (AMR) in heart transplantation. We believe that the appropriate reactants are those that best predict the adverse consequences of AMR and therefore tested various models using different reactants to find the best predictors of cardiovascular mortality in pathologically defined AMR.


METHODS
The study group included only patients in whom all immunofluorescence antibodies of interest had been tested on biopsy specimens obtained after 2002 when C4d was routinely added. We analyzed our data using 3 Cox proportional hazard models with time-varying covariates using an end point of cardiovascular mortality, as previously defined.


RESULTS
In 3,712 biopsy specimens from 422 patients, the 2-antibody model achieved a value of R(2) = 0.930 using C3d and C4d antibodies alone. A model that used 4 antibodies--C3d, C4d, human leukocyte antigen-D related (HLA-DR) and fibrin--was superior (R(2) = 0.988). The model that best predicted cardiovascular mortality included all 6 antibodies: HLA-DR, immunoglobulin (Ig) G, IgM, C3d, C4d, and fibrin (R(2) = 0.989). The models using 4 or 6 antibodies were significantly superior to the model using only C3d and C4d (for each interaction, p < 0.0001).


CONCLUSIONS
The combination of complement components, HLA-DR and fibrin, is valuable in defining AMR in patients at risk for allograft loss from cardiovascular causes. Fibrin is particularly important for detecting the presence of severe AMR, with a high likelihood of poor long-term patient outcome.
Revelo
Monica P
MP
George E Wahlen Veterans Affairs Medical Center, Utah Transplantation Affiliated Hospitals, Salt Lake City, Utah, USA.
Stehlik
Josef
J
Miller
Dylan
D
Snow
Gregory L
GL
Everitt
Melanie D
MD
Budge
Deborah
D
Bader
Feras M
FM
Alharethi
Rami A
RA
Gilbert
Edward M
EM
Reid
Bruce B
BB
Selzman
Craig H
CH
Hammond
M Elizabeth H
ME
Kfoury
Abdallah G
AG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015933:Complement C3d / Q000378:metabolism; D015935:Complement C4b; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006084:Graft Rejection / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D006684:HLA-DR Antigens / Q000097:blood; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality* / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
D000906:Antibodies; D015415:Biomarkers; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d; D005337:Fibrin