Correlations between HLA-A, HLA-B and HLA-DRB1 Allele Polymorphisms and Childhood Susceptibility to Acquired Aplastic Anemia

Abstract

To investigate the correlations between polymorphisms of human leukocyte antigen (HLA)-A, HLA-B and HLA-DRB1 alleles and childhood susceptibility to aplastic anemia (AA), 80 children with AA were investigated. Among the 80 children, 74 had severe AA (SAA). Blood samples were collected from 109 healthy children as the controls. High-resolution genotyping of HLA-A, HLA-B and HLA-DRB1 alleles was conducted using polymerase chain reaction amplification with sequence-specific primers and polymerase chain reaction amplification with sequence-based typing. The expression frequencies of HLA-B*48:01 and DRB1*09:01 were significantly higher and the frequencies of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in the AA group compared with those in the control group. In addition, the frequencies of HLA-B*48:01 and DRB1*09:01 were significantly higher and the frequencies of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in the SAA group compared with those in the control group. HLA-B*48:01 and DRB1*09:01 were correlated with childhood AA, and thus they may be susceptibility genes for childhood SAA. HLA-B*51:01, DRB1*03:01 and DRB1*11:01 are expressed at low levels in children with AA.

Correlation analysis of severe aplastic anemia immunosuppressive therapy and human leukocyte antigen alleles in pediatric patients

“…In addition, it has been shown that HLA-DRB1*15 is associated with the immunosuppressive therapy of children with AA (11,13,14); children who were positive for HLA-DRB1*15 exhibited a good response to the simple cyclosporine A (CsA) treatment and enhanced immunosuppressive therapy. However, previous studies concerning the association of HLA with AA in different provinces of China have yielded inconsistent results (15,16), and IST-related studies of HLA are limited.…”

Molecular pathogenesis of acquired aplastic anemia

“…Ethnic differences in genetic predisposition to AA risk appear to be shaped by HLA allele variations although it is difficult to draw definitive conclusions from specific ethnic group observations due to differences in the linkage disequilibrium existing between HLA alleles in different populations. Specific HLA allelotypes have been associated with the presence of PNH clones, 41,42 increased [43][44][45][46] or decreased 44,47 susceptibility to developing AA, and some others with response to IST. 41,44 The underlying pathophysiologic mechanism appears to be an induction of immune attack by activation of autoreactive cytototoxic T-cell clonotypes against HSCs in a HLA-restricted pattern.…”

“…Specific HLA allelotypes have been associated with the presence of PNH clones, 41,42 increased [43][44][45][46] or decreased 44,47 susceptibility to developing AA, and some others with response to IST. 41,44 The underlying pathophysiologic mechanism appears to be an induction of immune attack by activation of autoreactive cytototoxic T-cell clonotypes against HSCs in a HLA-restricted pattern. 48 Recent focus has also been on the impact of somatic acquired mutations in the HLA class genes on AA-related autoimmunity.…”

Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia

“…The HLA-DRB1∗07 allele has been reported overexpressed in AA patients with no difference between adults and children, placing it as a susceptible allele for AA, at least in that cohort of Iranian subjects [35]. In addition, other candidate alleles predisposing to AA and SAA in children have been reported such as HLA-B∗48:01, HLA-DRB1∗09:01, and HLA-B14 [41, 42]. However, in the latter study [42], it was demonstrated that different HLA associations occur in children and adults; therefore any assumptions regarding HLA allele distribution between these groups should be made cautiously.…”

“…The allele HLA-DRB1∗13 appeared to be protective in SAA children of Turkish origin [43], as well as the HLA-DRB1∗03:01, HLA-DRB1∗11:01, and HLA-B∗51:01 alleles in Chinese children with AA [41]. Likewise, in a small cohort of Pakistani AA patients, HLA-DRB1∗03 had higher frequency in controls suggesting a putative protective role [33].…”