rs660 polymorphism in Ro52 (SSA1; TRIM 21) is a marker for age-dependent tolerance induction and efficiency of alloimmunization in sickle cell disease

Zohreh Tatari-Calderone, Caterina P. Minniti, Tonya Kratovil, Milica Stojakovic, Alison Vollmer, Igor Barjaktarevic, Ed Zhang, Albert Hoang, Naomi L.C. Luban, Stanislav Vukmanovic

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Abstract

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.

Original languageEnglish
Pages (from-to)64-70
Number of pages7
JournalMolecular Immunology
Volume47
Issue number1
DOIs
Publication statusPublished - 1 Nov 2009

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Keywords

  • Antibodies
  • Gene polymorphisms
  • Red blood cell transfusion
  • Sickle cell disease

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this

Tatari-Calderone, Z., Minniti, C. P., Kratovil, T., Stojakovic, M., Vollmer, A., Barjaktarevic, I., Zhang, E., Hoang, A., Luban, N. L. C., & Vukmanovic, S. (2009). rs660 polymorphism in Ro52 (SSA1; TRIM 21) is a marker for age-dependent tolerance induction and efficiency of alloimmunization in sickle cell disease. Molecular Immunology, 47(1), 64-70. https://doi.org/10.1016/j.molimm.2008.12.027