The PTPN22 R620W polymorphism is associated with severe bacterial infections after human leukocyte antigen geno-identical haematopoietic stem-cell transplantations.
PTPN22 is a negative regulator of T-cell activation. The C1858T PTPN22 polymorphism has been associated with autoimmune diseases. The role of PTPN22 in immune response and autoimmune diseases suggested that PTPN22 polymorphism could impact outcome of allogeneic hematopoietic stem-cell transplantations that is impaired by immunological and infectious complications. One hundred ninety-two patients who received a non-T-depleted bone marrow transplant from a human leukocyte antigen-identical sibling donor were included in this study. Donor PTPN22 C1858Tpolymorphism was not associated with severe acute graft-versus-host disease, relapse, survival, cytomegalovirus, and fungal infections, but significant with severe bacterial infections (24% for donor CC vs. 0% for donor CT+TT genotypes, P=0.003). The association was confirmed by a multivariate analysis (P=0.036, hazard ratio=2.28, 95% confidence interval=1.06-4.90). This could improve the genetic risk assessment of severe bacterial infections in allogeneic hematopoietic stem-cell transplantations.
Azarian
Mariam
M
Laboratoire d'Immunologie et d'Histocompatibilité, Inserm U662, Service d'Hématologie-Greffe de moelle, Hôpital Saint-Louis, CIB-HOG, AP-HP, Paris, France.
Busson
Marc
M
Rocha
Vanderson
V
Ribaud
Patricia
P
Peffault de Latour
Regis
R
Bleux
Hélène
H
Lepage
Virginia
V
Charron
Dominique
D
Toubert
Antoine
A
Socié
Gérard
G
Loiseau
Pascale
P
D000328:Adult; D001424:Bacterial Infections / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011183:Postoperative Complications / Q000382:microbiology*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D018570:Risk Assessment
D006680:HLA Antigens; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22