title: Immunogenetic heterogeneity in single-system and multisystem langerhans cell histiocytosis.
abstract: Langerhans cell histiocytosis is a rare disease with an unknown etiology and poorly understood pathogenesis. Immunologic, viral, and proliferative clonality causes have all been considered. To determine whether Langerhans cell histiocytosis and its two main subgroups, single-system and multisystem disease, are associated with HLA-A, -B, -Cw, or -DR alleles, a total of 84 patients <15 y of age at the time of diagnosis and of Nordic origin were analyzed, 82 for HLA class I and 76 for HLA class II. Stratification of the patients into two subgroups, single-system disease (skin only, and monostotic and polyostotic disease) and multisystem disease with or without organ dysfunction, showed that patients with single-system disease (17 of 45, 38%) more often (p = 0.00018 and, after correction, p = 0.029) had the phenotype HLA-DRB1*03 compared with patients with multisystem disease (1 of 31, 3%). In the patients with multisystem disease a nonsignificant reduction of the frequency of this phenotype was seen compared with controls (p = 0.02, uncorrected). In 14 of the patients with single-system disease, but none with multisystem disease, the deduced haplotype HLA-A*01, B*08, DRB1*03 was found. High-resolution typing, performed in nine patients, revealed that all had the HLA-A*0101, B*0801, DRB1*0301, DQB1*0201 alleles. Our findings suggest an immunogenetic heterogeneity in the two clinical entities of Langerhans cell histiocytosis and indicate that HLA-DRB1*03 may play a protective role against developing multisystem disease. Further studies to confirm these findings are desired.
authors.affiliation: Childhood Cancer Research Unit, Q6:05, Karolinska Hospital, S-171 76 Stockholm, Sweden. Cecilia.Bernstrand@kbh.ki.se
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bernstrand
authors.forename: Henrik
authors.initials: H
authors.lastname: Carstensen
authors.forename: Bodil
authors.initials: B
authors.lastname: Jakobsen
authors.forename: Arne
authors.initials: A
authors.lastname: Svejgaard
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: Olle
authors.initials: O
authors.lastname: Olerup
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003718:Denmark; D005260:Female; D018740:Genetic Heterogeneity; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006646:Histiocytosis, Langerhans-Cell / Q000235:genetics* / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D010641:Phenotype; D013548:Sweden
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen