TY - JOUR
T1 - rs660 polymorphism in Ro52 (SSA1; TRIM 21) is a marker for age-dependent tolerance induction and efficiency of alloimmunization in sickle cell disease
AU - Tatari-Calderone, Zohreh
AU - Minniti, Caterina P.
AU - Kratovil, Tonya
AU - Stojakovic, Milica
AU - Vollmer, Alison
AU - Barjaktarevic, Igor
AU - Zhang, Ed
AU - Hoang, Albert
AU - Luban, Naomi L.C.
AU - Vukmanovic, Stanislav
PY - 2009/11
Y1 - 2009/11
N2 - Patients with sickle cell disease (SCD) who receive red blood cell (RBC) transfusions have a higher rate of anti-RBC (allo and auto) antibody development than other transfused subjects. We hypothesized that an incidence and/or kinetics of RBC-specific antibody formation in SCD patients is influenced by a linked inheritance of the hemoglobin beta S (HbβS) allele and a polymorphism rs660C/T in the neighboring Ro52 gene. We found that 75% of C/T heterozygous and only 30.8% of T/T homozygous patients that developed antibodies were first transfused before the age of five. In addition, there was a significant inverse correlation between time of exposure to antigen or number of transfusions received and the age when T/T patients received first transfusion, indicating progressive development of competence of their immune system. In contrast, this correlation was not observed in patients with C/T genotype. Finally, increased expression of Ro52 was associated with the presence of the T/T genotype. These results suggest that rs660 polymorphism is a marker of efficiency of tolerance induction in early childhood and immune competence development to RBC antigens in SCD patients of pre-teen/teen age.
AB - Patients with sickle cell disease (SCD) who receive red blood cell (RBC) transfusions have a higher rate of anti-RBC (allo and auto) antibody development than other transfused subjects. We hypothesized that an incidence and/or kinetics of RBC-specific antibody formation in SCD patients is influenced by a linked inheritance of the hemoglobin beta S (HbβS) allele and a polymorphism rs660C/T in the neighboring Ro52 gene. We found that 75% of C/T heterozygous and only 30.8% of T/T homozygous patients that developed antibodies were first transfused before the age of five. In addition, there was a significant inverse correlation between time of exposure to antigen or number of transfusions received and the age when T/T patients received first transfusion, indicating progressive development of competence of their immune system. In contrast, this correlation was not observed in patients with C/T genotype. Finally, increased expression of Ro52 was associated with the presence of the T/T genotype. These results suggest that rs660 polymorphism is a marker of efficiency of tolerance induction in early childhood and immune competence development to RBC antigens in SCD patients of pre-teen/teen age.
KW - Antibodies
KW - Gene polymorphisms
KW - Red blood cell transfusion
KW - Sickle cell disease
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U2 - 10.1016/j.molimm.2008.12.027
DO - 10.1016/j.molimm.2008.12.027
M3 - Review article
C2 - 19201475
AN - SCOPUS:70350618088
SN - 0161-5890
VL - 47
SP - 64
EP - 70
JO - Molecular Immunology
JF - Molecular Immunology
IS - 1
ER -