Alloimmunization in sickle cell disease: Changing antibody specificities and association with chronic pain and decreased survival

Journal Article

© 2014 AABB. Background Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD. Study Design and Methods Adult SCD patients were enrolled in a study of outcome-modifying genes in SCD. Historical records of patients with SCD at two participating institutions were reviewed for data on antigen phenotype and alloimmunization. Differences in demographic, clinical, and laboratory findings; end-organ damage; and overall disease severity were then compared between alloimmunized and nonalloimmunized patients. Results Of 319 patients, 87 (27%) were alloimmunized. Alloantibody specificities differed from those previously described, especially due to the significantly higher frequency of anti-S. Although alloimmunization was not associated with frequency of vasoocclusive episodes, a higher percentage of alloimmunized patients had chronic pain, as defined by daily use of short-acting narcotics (p = 0.006), long-acting narcotics (p = 0.013), or both (p = 0.03). Additionally, alloimmunized patients had poorer survival (hazard ratio, 1.92; p = 0.01) and were more likely to have avascular necrosis (p = 0.024), end-organ damage (p = 0.049), and red blood cell autoantibodies (p < 0.001), even after controlling for the effects of age, sex, and hemoglobin diagnosis. Alloimmunization was not associated with other SCD-related complications, such as acute chest syndrome or stroke. Conclusion Alloimmunization in SCD may be associated with chronic pain, risk of end-organ damage, and shorter survival. These novel findings suggest new directions for the investigation of immune response-mediated pathways common to alloimmunization and chronic pain.

Full Text

Duke Authors

Cited Authors

  • Telen, MJ; Afenyi-Annan, A; Garrett, ME; Combs, MR; Orringer, EP; Ashley-Koch, AE

Published Date

  • June 1, 2015

Published In

Volume / Issue

  • 55 / 6

Start / End Page

  • 1378 - 1387

Electronic International Standard Serial Number (EISSN)

  • 1537-2995

International Standard Serial Number (ISSN)

  • 0041-1132

Digital Object Identifier (DOI)

  • 10.1111/trf.12940

Citation Source

  • Scopus