Lack of Duffy antigen expression is associated with organ damage in patients with sickle cell disease.
BACKGROUND
The Duffy glycoprotein (Fy) on red blood cells (RBCs) has been hypothesized to promote clearance of inflammatory cytokines, which may play a role in the pathogenesis of vasoocclusion in sickle cell disease (SCD). Persons with the African-type Fy(a-b-) phenotype--whose RBCs lack expression of Duffy--may less efficiently clear inflammatory cytokines. Therefore, the Duffy-negative genotype may be associated with more severe disease among patients with SCD.


METHODS
Genotyping was performed on blood samples from 249 adult patients with HbSS at the Duffy gene (FY) locus GATA site (rs2814778) that determines RBC expression of Duffy antigens. Patients with discordant genotype and phenotype data were excluded (n = 12). Differences in demographic, clinical and laboratory findings, end-organ damage, and overall disease severity were compared between FY+ and FY- patients.


RESULTS
Of the 237 patients studied, 174 (73%) were FY-. FY+ patients had a higher mean white blood cell (WBC) count (13.2 x 10(9) +/- 4.1 x 10(9)/L vs. 11.8 x 10(9) +/- 3.3 x 10(9)/L; p = 0.03) and higher rates of treatment with hydroxyurea (72% vs. 49%; p = 0.002). In contrast, FY- status was strongly associated with chronic organ damage (85% of FY- patients vs. 65% of FY+ patients; p = 0.018) and proteinuria (32% vs. 12%; p = 0.02). These associations remained, even after controlling for the effects of age and sex.


CONCLUSIONS
Duffy genotype may be a potential biomarker for the development of end-organ damage in SCD, particularly kidney dysfunction. The association of both WBC counts and hydroxyurea use with Duffy expression provides another avenue for investigation of the biologic role of this protein.
Afenyi-Annan
Araba
A
Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina, USA. nyaniba@med.unc.edu
Kail
Melanie
M
Combs
Martha R
MR
Orringer
Eugene P
EP
Ashley-Koch
Allison
A
Telen
Marilyn J
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications / Q000235:genetics*; D004375:Duffy Blood-Group System / Q000235:genetics* / Q000378:metabolism*; D004912:Erythrocytes / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology; D007958:Leukocyte Count; D016015:Logistic Models; D008171:Lung Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D012720:Severity of Illness Index
C473745:ACKR1 protein, human; D004375:Duffy Blood-Group System; D005819:Genetic Markers; D011956:Receptors, Cell Surface