rs660 polymorphism in Ro52 (SSA1; TRIM21) is a marker for age-dependent tolerance induction and efficiency of alloimmunization in sickle cell disease.
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 (HbbetaS) 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.
Tatari-Calderone
Zohreh
Z
Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010-2970, USA.
Minniti
Caterina P
CP
Kratovil
Tonya
T
Stojakovic
Milica
M
Vollmer
Alison
A
Barjaktarevic
Igor
I
Zhang
Ed
E
Hoang
Albert
A
Luban
Naomi L C
NL
Vukmanovic
Stanislav
S
D000293:Adolescent; D000367:Age Factors; D000755:Anemia, Sickle Cell / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D017707:Erythrocyte Transfusion / Q000009:adverse effects; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D007114:Immunization; D007121:Immunocompetence; D007519:Isoantigens; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012261:Ribonucleoproteins / Q000235:genetics* / Q000276:immunology; D055815:Young Adult; D000099207:SS-A Antigen
D015415:Biomarkers; D007519:Isoantigens; D012261:Ribonucleoproteins; D000099207:SS-A Antigen