TY - JOUR
T1 - The conundrum of HLA-DRB1*14
T2 - 01/*14:54 and HLA-DRB3*02: 01/*02:02 mismatches in unrelated hematopoietic SCT
AU - Pasi, A.
AU - Crocchiolo, R.
AU - Bontempelli, M.
AU - Carcassi, C.
AU - Carella, G.
AU - Crespiatico, L.
AU - Garbarino, L.
AU - Mascaretti, L.
AU - Mazzi, B.
AU - Mazzola, G.
AU - Miotti, V.
AU - Porfirio, B.
AU - Tagliaferri, C.
AU - Valentini, T.
AU - Vecchiato, C.
AU - Fleischhauer, K.
AU - Sacchi, N.
AU - Bosi, A.
AU - Martinetti, M.
PY - 2011/7
Y1 - 2011/7
N2 - 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-DRB114 and HLA-DRB3 at-high resolution level; 31/103 pairs had HLA-DRB114 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.
AB - 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-DRB114 and HLA-DRB3 at-high resolution level; 31/103 pairs had HLA-DRB114 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.
KW - HLA-DRB1 exon 3 mismatch
KW - HLA-DRB3 mismatch
KW - outcome
KW - unrelated SCT
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UR - http://www.scopus.com/inward/citedby.url?scp=79960153343&partnerID=8YFLogxK
U2 - 10.1038/bmt.2010.246
DO - 10.1038/bmt.2010.246
M3 - Article
C2 - 20972469
AN - SCOPUS:79960153343
VL - 46
SP - 916
EP - 922
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 7
ER -