title: HLA-associated hemorrhagic fever with renal syndrome disease progression in slovenian patients.
abstract: Major histocompatibility complex (MHC) class I and class II genes regulate the balance between appropriate aggressive responses and invading pathogens while minimizing the destruction of host tissue. Several studies have shown that in hemorrhagic fever with renal syndrome (HFRS) patients, the disease outcome is determined by a complex interaction between the virus and immunopathologic and human genetic factors. In Slovenia, the severity of the disease caused by Puumala virus (PUUV) is significantly lower than that of HFRS due to Dobrava virus (DOBV). We have determined 23 different HLA-B and 12 different HLA-DRB1 types in Slovenian HFRS patients. Comparison of HLA frequencies between healthy individuals and HFRS patients showed no strong association with the susceptibility for hantaviral infection. Significant associations were recognized when the patient group was separated according to the virus responsible for the infection. DOBV-infected patients have a significantly higher frequency of HLA-B*35 than PUUV-infected patients. For HLA class II genes, the biggest difference between the PUUV- and DOBV-infected groups of patients was in HLA-DRB1*13, where this phenotype was more frequent in PUUV-infected patients, especially in the severe form of the disease. HLA-B*07 could play a protective role in PUUV-caused HFRS in the Slovenian population. Our study shows diverse associations of HLA molecules with DOBV- and PUUV-induced HFRS, and therefore, we presume that different hantaviruses are presented differently through the same HLA molecules and that this might lead to either a more severe or a milder form of the disease. In line with this idea, we have noticed that HLA-B*35 might be a genetic risk factor for DOBV infection in the Slovenian population.
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia.
authors.forename: Misa
authors.initials: M
authors.lastname: Korva
authors.forename: Ana
authors.initials: A
authors.lastname: Saksida
authors.forename: Sabina
authors.initials: S
authors.lastname: Kunilo
authors.forename: Blanka
authors.initials: B
authors.lastname: Vidan Jeras
authors.forename: Tatjana
authors.initials: T
authors.lastname: Avsic-Zupanc
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000145:classification / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000145:classification / Q000235:genetics* / Q000276:immunology; D006476:Orthohantavirus / Q000276:immunology / Q000472:pathogenicity*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D006650:Histocompatibility Testing; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D029262:Puumala virus / Q000276:immunology / Q000472:pathogenicity*; D012720:Severity of Illness Index; D017524:Slovenia; D013045:Species Specificity
chemical_list: D000914:Antibodies, Viral; D015235:HLA-B Antigens; D059811:HLA-DRB1 Chains; D007075:Immunoglobulin M