Possible Relationship between the HLA-DRA1 Intron Haplotype of Three Single-Nucleotide Polymorphisms in Intron 1 of the HLA-DRA1 Gene and Autoantibodies in Children at Increased Genetic Risk for Autoimmune Type 1 Diabetes

Andersson Svärd, AgnesLund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Pediatrisk endokrinologi,Celiac Disease and Diabetes Unit,Lund University Research Groups,Paediatric Endocrinology,Skåne University Hospital (author)

Recently, a haplotype of three single-nucleotide polymorphisms (tri-SNP) in intron 1 of the HLA-DRA1 gene was found to be strongly associated with type 1 diabetes risk in HLA-DR3/3 individuals. The tri-SNP reportedly function as “expression quantitative trait loci,” modulating HLA-DR and -DQ expression. The aim was to investigate HLA-DRA1 tri-SNPs in relation to extended HLA class II haplotypes and human peripheral blood cell HLA-DQ cell-surface median fluorescence intensity (MFI), the first-appearing islet autoantibody, and autoimmunity burden. A total of 67 healthy subjects (10–15 y) at increased HLA risk for type 1 diabetes and with (n = 54) or without (n = 13) islet autoantibodies were followed longitudinally in the Diabetes Prediction in Skåne study. Among four tri-SNPs, AGG (n = 67), GCA (n = 47), ACG (n = 11), and ACA (n = 9), HLA-DQ cell-surface MFI on CD4+ T cells was lower in AGG than GCA (p = 0.030) subjects. Cumulative autoimmunity burden was associated with reduced HLA-DQ cell-surface MFI in AGG compared with GCA in CD16+ cells (p = 0.0013), CD4+ T cells (p = 0.0018), and CD8+ T cells (p = 0.016). The results suggest that HLA-DRA1 tri-SNPs may be related to HLA-DQ cell-surface expression and autoimmunity burden.

Benatti, ElinLund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)el8545be (author)
Lundgren, MarkusLund University,Lunds universitet,Pediatrisk endokrinologi,Forskargrupper vid Lunds universitet,Paediatric Endocrinology,Lund University Research Groups,Central Hospital Kristianstad,Skåne University Hospital(Swepub:lu)med-mn2 (author)
Lernmark, AkeLund University,Lunds universitet,Celiaki och diabetes,Forskargrupper vid Lunds universitet,Celiac Disease and Diabetes Unit,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-ale (author)
Maziarz, MarlenaLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups,Skåne University Hospital(Swepub:lu)ma4353ma (author)
Elding Larsson, HelenaLund University,Lunds universitet,Pediatrisk endokrinologi,Forskargrupper vid Lunds universitet,Paediatric Endocrinology,Lund University Research Groups,Skåne University Hospital(Swepub:lu)pedi-hla (author)
Celiaki och diabetesForskargrupper vid Lunds universitet (creator_code:org_t)
DiPiS Study Group

In:ImmunoHorizons: The American Association of Immunologists6:8, s. 614-6292573-7732

By the author/editor: Andersson Svärd, ...; Benatti, Elin; Lundgren, Markus; Lernmark, Ake; Maziarz, Marlena; Elding Larsson, ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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