title: Infectious complications in sickle cell disease are influenced by HLA class II alleles.
abstract: Despite systematic antibiotic therapy, severe infections (septicemia, meningitis, or osteomyelitis) are a major cause of mortality and morbidity in children with sickle cell disease (SCD). In this study, we explored the possibility that polymorphism at the human leukocyte antigen (HLA) locus might constitute an immunogenetic modifying factor to the intrinsic susceptibility to infection in patients with SCD. A cohort of 80 SCD patients living in Paris, 43 with at least one major infectious complication and 37 without infections, were typed for HLA class II loci by polymerase chain reaction-sequence-specific primers (PCR-SSP). We found that significantly more patients without infections carry the HLA class II DRB1*15 specificity than did patients with infections (21.6% in the first group, versus 4.7% in the second group; chi(2) = 10.47, p(c) = 0.01), supporting a protective effect of this allele. Conversely, significantly more patients were found to carry the DQB1*03 specificity within the group of severe infections, supporting a negative effect (34.9% versus 12.2%, chi(2) = 9.41, p(c) = 0.01). These findings suggest a direct involvement of HLA polymorphism in the development of major infections in SCD. Together with previous data on polymorphism of the Fc receptor and of the mannose-binding lectin, they provide evidence for a polygenic immunomodulation of the constitutively increased infectious risk in SCD.
authors.affiliation: Laboratoire d'Immunologie et d'Histocompatibilité, AP-HP, IUH, and INSERM U396, Hôpital Saint-Louis, Paris, France. tamouza@histo.chu-stlouis.fr
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Neonato
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: François
authors.initials: F
authors.lastname: Marzais
authors.forename: Robert
authors.initials: R
authors.lastname: Girot
authors.forename: Dominique
authors.initials: D
authors.lastname: Labie
authors.forename: Jacques
authors.initials: J
authors.lastname: Elion
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000235:genetics*; D016470:Bacteremia / Q000473:pathology; D001424:Bacterial Infections / Q000150:complications*; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006681:HLA-D Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000378:metabolism; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008581:Meningitis / Q000382:microbiology / Q000473:pathology; D010019:Osteomyelitis / Q000382:microbiology / Q000473:pathology; D011008:Pneumococcal Infections / Q000150:complications; D011110:Polymorphism, Genetic / Q000235:genetics; D012480:Salmonella Infections / Q000150:complications; D013203:Staphylococcal Infections / Q000150:complications
chemical_list: D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains