MICA-129 genotype, soluble MICA, and anti-MICA antibodies as biomarkers of chronic graft-versus-host disease.
The MHC class I-related chain A (MICA) molecules exist as membrane-bound and soluble isoforms and are encoded by a polymorphic gene. Their genetic and phenotype characteristics have been studied in various pathologic settings but not in the context of hematopoietic stem cell transplantation (HSCT). Here, we evaluated whether MICA-related features namely MICA-129 gene polymorphism, serum levels of soluble MICA (sMICA) and anti-MICA antibodies (MICA Abs) before and after HSCT could influence the incidence of chronic graft-versus-host disease (cGVHD) and relapse of their disease in 211 HLA-identical sibling pairs and in a subset of 116 recipients, respectively. Although the MICA-129 val/val genotype and elevated sMICA serum levels after HSCT are independently associated with the incidence of cGVHD (P = .002 and .001) regardless of history of acute GVHD, the presence of MICA Abs before transplantation confers protection against cGVHD (P = .04). There is an inverse relationship between MICA Abs and sMICA, suggesting an antibody-based neutralization of deleterious effects of sMICA. Similarly, these genetic and phenotype characteristics of MICA influence the incidence of relapse. Altogether, these data suggest that the studied MICA genotype and phenotype specificities could be used as relevant biomarkers for cGVHD monitoring.
Laboratoire d'Immunologie et d'Histocompatibilité, Centre d'Innovations Biomédicales-Hématologie/Oncologie/Greffe (CIB-HOG), Institut Universitaire d'Hématologie (IUH), and Inserm, UMRS, 940, Hôpital Saint-Louis, Paris, France.
Wahid
W
Boukouaci
Marc
M
Busson
Régis
R
Peffault de Latour
Vanderson
V
Rocha
Caroline
C
Suberbielle
Djaouida
D
Bengoufa
Nicolas
N
Dulphy
Philippe
P
Haas
Catherine
C
Scieux
Habiba
H
Amroun
Eliane
E
Gluckman
Rajagopal
R
Krishnamoorthy
Antoine
A
Toubert
Dominique
D
Charron
Gérard
G
Socié
Ryad
R
Tamouza
D000293:Adolescent; D000328:Adult; D000538:Aluminum Silicates; D000906:Antibodies / Q000032:analysis / Q000276:immunology; D015415:Biomarkers / Q000032:analysis* / Q000097:blood; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006086:Graft vs Host Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000097:blood / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D010641:Phenotype; D011110:Polymorphism, Genetic; D012995:Solubility; D013997:Time Factors; D055815:Young Adult
D000538:Aluminum Silicates; D000906:Antibodies; D015415:Biomarkers; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C011934:mica