The conundrum of HLA-DRB1*14:01/*14:54 and HLA-DRB3*02:01/*02:02 mismatches in unrelated hematopoietic SCT.
Uncertainty still exists on the role of polymorphisms outside the HLA-DRB1 binding site or inside the HLA-DRB3 binding groove in unrelated hematopoietic SCT (HSCT). The ideal model to solve the conundrum consists of the transplants mismatched for HLA-DRB1*14:01/*14:54 and/or for HLA-DRB3*02:01/*02:02. A task force was set up in Italy to recruit transplanted pairs defined as HLA-DRB1*14:01 before 2006, the year crucial for the proper definition of the HLA-DRB1*14:54 allele in molecular biology. Out of 2723 unrelated pairs, 189 transplanted in Italy from 1995 to 2006 were HLA-DRB1*14:01 positive; 103/189 pairs with good historical DNA were retyped for HLA-DRB1*14 and HLA-DRB3 at-high resolution level; 31/103 pairs had HLA-DRB1*14 and/or HLA-DRB3 mismatched; 99/103, having complete clinical data, underwent statistical analysis for OS, TRM, disease-free survival and acute and chronic GvHD. No significant involvement of HLA-DRB1*14:01/*14:54 or HLA-DRB3*02:01/*02:02 mismatches was found, either alone or combined. Our findings suggest that disparities at exon 3 of the HLA-DRB1 gene seem unlikely to influence the outcome after HSCT. The same may be envisaged for HLA-DRB3(*)02:01 and (*)02:02 alleles which, although differing in the Ag binding site, seem unable to modulate an appreciable immune response in an HSCT setting.
Immunogenetics Laboratory, Immunohematology and Transfusion Center, IRCCS Foundation, Policlinico San Matteo, Pavia, Italy.
A
A
Pasi
R
R
Crocchiolo
M
M
Bontempelli
C
C
Carcassi
G
G
Carella
L
L
Crespiatico
L
L
Garbarino
L
L
Mascaretti
B
B
Mazzi
G
G
Mazzola
V
V
Miotti
B
B
Porfirio
C
C
Tagliaferri
T
T
Valentini
C
C
Vecchiato
K
K
Fleischhauer
N
N
Sacchi
A
A
Bosi
M
M
Martinetti
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D059811:HLA-DRB1 Chains / Q000276:immunology*; D059826:HLA-DRB3 Chains / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains