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Polymorphisms and haplotypes of IL2RA, IL-10, IFN-γ, IRF5, and CCR2 are associated with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children
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  • Nannan Tang,
  • Junbin Huang,
  • Chun Chen,
  • Xiaojun Wu,
  • Hong Xu,
  • Guohua Chen,
  • Hongman Xue
Nannan Tang
The Seventh Affiliated Hospital Sun Yat-sen University
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Junbin Huang
The Seventh Affiliated Hospital Sun Yat-sen University
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Chun Chen
The Seventh Affiliated Hospital Sun Yat-sen University
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Xiaojun Wu
Sun Yat-sen Memorial Hospital , Sun Yat-sen University, Department of Pediatrics
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Hong Xu
The 2nd affiliated hospital of Sun Yat-Sen university
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Guohua Chen
Huizhou First Hospital
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Hongman Xue
The Seventh Affiliated Hospital Sun Yat-sen University
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Abstract

Objective: Cytokine storms are central to the development of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). Previous studies showed that single nucleotide polymorphisms (SNPs) of cytokine genes may be associated with the development of EBV-HLH in children. We investigated the associations between SNPs and haplotypes of interleukin-2 receptor subunit alpha (IL2RA), interleukin-10 (IL-10), interferon gamma (IFN-γ), IFN regulatory factor 5 (IRF5), and C-C chemokine receptor 2 (CCR2) and susceptibility to EBV-HLH in children. Methods: 66 children with EBV-HLH and 58 healthy EBV-seropositive controls were enrolled in the study. SNPs of IL2RA rs2104286, rs12722489, and rs11594656, IL-10 rs1800896, rs1800871, and rs1800872, IFN-γ rs2430561, IRF5 rs2004640, and CCR2 rs1799864 were assayed and genotyped using the SNaPshot technique. Results: The frequencies of the AA genotype and A allele of IL2RA rs2104286 and IL-10 rs1800896, and the CC genotype and C allele of IL-10 rs1800872 were significantly higher in the EBV-HLH group compared with those in the control group, respectively. The frequencies of genotypes and alleles of IL2RA rs2104286, IL-10 rs1800871, IFN-γ rs2430561, IRF5 rs2004640, and CCR2 rs1799864 were similar in both groups. In addition, the IL2RA AGT (rs2104286-rs12722489-rs11594656) and IL-10 ACC (rs1800896-rs1800871-rs1800872) haplotypes were also significantly more frequent in the EBV-HLH group. Conclusions: The SNPs of IL2RA rs2104286, IL-10 rs1800896 and rs1800872 and the haplotypes of IL2RA AGT and IL-10 ACC are highly associated with susceptibility to EBV-HLH in children.

Peer review status:ACCEPTED

25 Sep 2020Submission Checks Completed
25 Sep 2020Assigned to Editor
25 Sep 2020Submitted to Pediatric Blood & Cancer
04 Oct 2020Reviewer(s) Assigned
30 Oct 2020Review(s) Completed, Editorial Evaluation Pending
02 Nov 2020Editorial Decision: Revise Major
28 Jan 20211st Revision Received
28 Jan 2021Submission Checks Completed
28 Jan 2021Assigned to Editor
31 Jan 2021Reviewer(s) Assigned
02 Mar 2021Review(s) Completed, Editorial Evaluation Pending
03 Mar 2021Editorial Decision: Revise Minor
03 Apr 2021Submission Checks Completed
03 Apr 2021Assigned to Editor
03 Apr 20212nd Revision Received
10 Apr 2021Review(s) Completed, Editorial Evaluation Pending
10 Apr 2021Editorial Decision: Revise Minor
11 Apr 2021Assigned to Editor
11 Apr 2021Submission Checks Completed
11 Apr 20213rd Revision Received
14 Apr 2021Review(s) Completed, Editorial Evaluation Pending
14 Apr 2021Editorial Decision: Accept