title: The distribution of HLA alleles among children with atopic asthma in Croatia.
abstract: Allergic asthma is a multifactorial disease involving well known environmental factors and less identified genetic components. In several studies the HLA genes have been implicated in the development of asthma and atopy, but the importance of these associations remains unclear. The aim of the present study was to analyse the distribution of specificities at HLA class I loci (-A and -B) and HLA class II locus (-DRB1) in a group of 143 Croatian children with atopic asthma, regarding total serum IgE and specific IgE against common inhalant allergens, as well as their connection with different asthmatic phenotypes and to identify HLA genotype which increases the risk for atopy or asthma or which has a protective effect. As controls we used a group of 163 healthy unrelated individuals. HLA class I antigens were determined by serology, while DRB1 specificities were detected by polymerase-chain reaction amplification and hybridisation with sequence specific oligonucleotide probes method (PCR-SSOP). We found no significant correlation between any of the HLA-A antigens and asthma, atopy or associated atopic phenotypes. At HLA-B locus, HLA-B8 antigen was significantly increased among asthmatic patients (p = 0.002), patients with high total serum IgE (p = 0.002), as well as among patients sensitizated to Dermatophagoides pteronyssinus (Der p) (p = 0.014) and among patients sensitizated to Der p + Dactylis glomerata (Dact g) or Ambrosia elatior (Amb a) (p = 0.004). Among HLA-DRB1 specificities, HLA-DRB1 *01 showed positive correlation with asthma and atopy (p = 0.034), while HLA-DRB1*03 specificity was observed with significantly higher frequency among patients with total serum IgE > or = 400 KU/L (p = 0.048). HLA-DRB1*16 specificity was observed with significantly lower frequency among patients with asthma only in comparison to healthy controls (p = 0.027) and to patients with asthma and allergic rhinitis (p = 0.005). In conclusion, our data suggest that HLA specificities play a relevant role in predisposition to asthma, as well as in different clinical forms of atopic diseases. HLA-B8, HLA-DRB1*01 and HLA-DRB1*03 genotype increases the risk for atopic asthma and high serum IgE.
authors.affiliation: University of Zagreb, "Sestre milosrdnice" University Hospital Center, Children's Hospital Zagreb, Department of Pulmonology, Allergology and Clinical Immunology, Zagreb, Croatia. irena.ivkovic.jurekovic@kbcsm.hr
authors.forename: Irena
authors.initials: I
authors.lastname: Ivković-Jureković
authors.forename: Renata
authors.initials: R
authors.lastname: Zunec
authors.forename: Vesna
authors.initials: V
authors.lastname: Balog
authors.forename: Zorana
authors.initials: Z
authors.lastname: Grubić
mesh_terms: D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017523:Croatia; D005260:Female; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology; D008297:Male
chemical_list: D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I