Influence of HLA-DRB alleles on haemorrhagic fever with renal syndrome in a Chinese Han population in Hubei Province, China

Abstract

Specific human leucocyte antigen (HLA) alleles are considered a genetic risk factor for the progression of haemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses. The aim of this study was to establish whether HLA-DRB alleles are associated with the severity of HFRS caused by different types of hantaviruses in a Chinese Han population from Hubei Province of central China. Twenty-two specific HLA-DRB alleles were analysed by sequence-specific primer-polymerase chain reaction (SSP-PCR) in 100 HFRS patients and 213 healthy volunteers. Associations of HLA-DRB alleles with the severity and clinical parameters of HFRS caused by Hantaan virus (HTNV) or Seoul virus (SEOV) infection were evaluated. Six alleles (HLA-DRB1*0401-0411, HLA-DRB1*1001, HLA-DRB1*1101-1105, HLA-DRB1*1201-1202, HLA-DRB1*1305 and DRB5*0101-0201) demonstrated strong associations with HFRS caused by HTNV and SEOV infections. Further comparison of these HLA-DRB1 allele frequencies between HFRS patients with differing severities and healthy controls demonstrated that the HLA-DRB1*0401-0411, HLA-DRB1*1001 and DRB1*1305 alleles were more frequent in the moderate course of HTNV-infected HFRS. Meanwhile, the DRB1*1101-1105 allele was more frequently observed in the severe course of HTNV-infected HFRS. We also found that the HLA-DRB1*1201-1202 allele frequency was higher in the moderate course of SEOV-infected HFRS, whereas the DRB5*0101-0201 allele may play a protective role in moderate HFRS caused by both HTNV and SEOV infections. These results provide evidence of the influence of HLA-DRB on the severity of HFRS and confirm the effect of HLA-DRB on HFRS during different types of hantavirus infection in a Chinese Han population in Hubei Province, China.

Construction of a Seasonal Difference-Geographically and Temporally Weighted Regression (SD-GTWR) Model and Comparative Analysis with GWR-Based Models for Hemorrhagic Fever with Renal Syndrome (HFRS) in Hubei Province (China)

“…The climate of each season varies largely. Previous studies have demonstrated that outbreaks of HFRS epidemics were strongly related with climate influencing factors [6], and the HFRS cases in Hubei Province displayed a bimodal distribution for each year [32,33]. From Figure 1 and Figure 3, it also appears that two peaks happen in a year (12 months).…”

Research Progress on the Pathogenesis of Hemorrhagic Fever with Renal Syndrome

“…In recent years, many domestic studies have shown that severe Han Chinese patients with HFRS have high gene frequencies of HLA-DRB1*46, HLA-B*46-DRB1*09 and HLA-B*51-DRB1*09. [40,41] A study also showed that HLA-A2 and B35 restricted HTNV nucleoprotein CD8 + T-cell epitope-specific immune response were correlates with mild HFRS, which demonstrated the severity of the disease is related to the host HLA gene frequency. [34]…”

Rapid humoral immune responses are required for recovery from haemorrhagic fever with renal syndrome patients

“…The CD8 low CD100 − subset is also activated and subsequently expresses more cytolytic effector molecules to combat HTNV infections [7]. It has also been noted that individuals harbouring human leukocyte antigen (HLA) alleles with HLA types B8, DRB1*0301 and DRB1*1101-1105 usually have higher viral loads, increasing the risk of developing severe disease [8][9][10]. Although virusspecific IgM is detectable simultaneously with the occurrence of clinical symptoms, and IgG of various subtypes is subsequently developed against viral structural proteins, the systematic mechanisms of virusspecific humoral responses to HTNV infection and their roles in the recovery are incompletely understood [11,12].…”