title: Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Division of Hematology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Telen
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Araba
authors.initials: A
authors.lastname: Afenyi-Annan
authors.affiliation: Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Garrett
authors.affiliation: Transfusion Service, Duke Hospital, Durham, North Carolina.
authors.forename: Martha R
authors.initials: MR
authors.lastname: Combs
authors.affiliation: Department of Medicine, Division of Hematology & Oncology, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Orringer
authors.affiliation: Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications* / Q000276:immunology* / Q000401:mortality*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood; D001803:Blood Transfusion / Q000706:statistics & numerical data; D059350:Chronic Pain / Q000097:blood / Q000150:complications*; D005260:Female; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016036:Seroepidemiologic Studies; D012720:Severity of Illness Index; D065227:Transfusion Reaction; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007518:Isoantibodies