Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1 diabetes

Jody Ye; Anna E Long; James A Pearson; Hazel Taylor; Polly J Bingley; Alistair J K Williams; Kathleen M Gillespie

doi:10.1007/s00125-015-3702-9

Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1 diabetes

Jody Ye, Anna E Long, James A Pearson, Hazel Taylor, Polly J Bingley, Alistair J K Williams, Kathleen M Gillespie

Research output: Contribution to journal › Article (Academic Journal)

4 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: The rate of progression from islet autoimmunity to clinical type 1 diabetes depends on the rate of beta cell destruction. The HLA-A*24 gene is associated with early diabetes onset, but previous studies have shown attenuated humoral responses to islet antigens in individuals with both recent and long-standing type 1 diabetes carrying HLA-A*24. We aimed to establish whether HLA-A*24 is also associated with attenuated humoral responses in individuals at high risk of type 1 diabetes.

METHODS: We established HLA-A*24, DQ and rs9258750 (an HLA-A*24 tagged single-nucleotide polymorphism) genotype, as well as GAD, zinc transporter 8 (ZnT8), insulin, islet antigen-2 (IA-2), and IA-2β autoantibody status in 373 islet cell antibody-positive first-degree relatives participating in the European Nicotinamide Diabetes Intervention Trial.

RESULTS: Univariate regression analyses showed that humoral responses to GAD, ZnT8 and insulin were less common in relatives carrying HLA-A*24. The prevalence of GAD and ZnT8 autoantibodies remained negatively associated with HLA-A*24 and rs9258750 after adjusting for age, sex, proband relationship and HLA class II genotype.

CONCLUSIONS/INTERPRETATION: HLA-A*24 is associated with attenuated humoral responses in individuals at high risk of type 1 diabetes, and this may reflect a distinct phenotype of rapid beta cell loss.

Original language	English
Pages (from-to)	2284-7
Number of pages	4
Journal	Diabetologia
Volume	58
Issue number	10
DOIs	https://doi.org/10.1007/s00125-015-3702-9
Publication status	Published - Oct 2015

Access to Document

10.1007/s00125-015-3702-9

Fingerprint Dive into the research topics of 'Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1 diabetes'. Together they form a unique fingerprint.

Cite this

Ye, J., Long, A. E., Pearson, J. A., Taylor, H., Bingley, P. J., Williams, A. J. K., & Gillespie, K. M. (2015). Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1 diabetes. Diabetologia, 58(10), 2284-7. https://doi.org/10.1007/s00125-015-3702-9

@article{d5658eb0015143afb1ca5585a3b014b1,

title = "Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1 diabetes",

abstract = "AIMS/HYPOTHESIS: The rate of progression from islet autoimmunity to clinical type 1 diabetes depends on the rate of beta cell destruction. The HLA-A*24 gene is associated with early diabetes onset, but previous studies have shown attenuated humoral responses to islet antigens in individuals with both recent and long-standing type 1 diabetes carrying HLA-A*24. We aimed to establish whether HLA-A*24 is also associated with attenuated humoral responses in individuals at high risk of type 1 diabetes.METHODS: We established HLA-A*24, DQ and rs9258750 (an HLA-A*24 tagged single-nucleotide polymorphism) genotype, as well as GAD, zinc transporter 8 (ZnT8), insulin, islet antigen-2 (IA-2), and IA-2β autoantibody status in 373 islet cell antibody-positive first-degree relatives participating in the European Nicotinamide Diabetes Intervention Trial.RESULTS: Univariate regression analyses showed that humoral responses to GAD, ZnT8 and insulin were less common in relatives carrying HLA-A*24. The prevalence of GAD and ZnT8 autoantibodies remained negatively associated with HLA-A*24 and rs9258750 after adjusting for age, sex, proband relationship and HLA class II genotype.CONCLUSIONS/INTERPRETATION: HLA-A*24 is associated with attenuated humoral responses in individuals at high risk of type 1 diabetes, and this may reflect a distinct phenotype of rapid beta cell loss.",

author = "Jody Ye and Long, {Anna E} and Pearson, {James A} and Hazel Taylor and Bingley, {Polly J} and Williams, {Alistair J K} and Gillespie, {Kathleen M}",

year = "2015",

month = oct,

doi = "10.1007/s00125-015-3702-9",

language = "English",

volume = "58",

pages = "2284--7",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Berlin Heidelberg",

number = "10",

}

TY - JOUR

T1 - Attenuated humoral responses in HLA-A*24-positive individuals at risk of type 1 diabetes

AU - Ye, Jody

AU - Long, Anna E

AU - Pearson, James A

AU - Taylor, Hazel

AU - Bingley, Polly J

AU - Williams, Alistair J K

AU - Gillespie, Kathleen M

PY - 2015/10

Y1 - 2015/10

N2 - AIMS/HYPOTHESIS: The rate of progression from islet autoimmunity to clinical type 1 diabetes depends on the rate of beta cell destruction. The HLA-A*24 gene is associated with early diabetes onset, but previous studies have shown attenuated humoral responses to islet antigens in individuals with both recent and long-standing type 1 diabetes carrying HLA-A*24. We aimed to establish whether HLA-A*24 is also associated with attenuated humoral responses in individuals at high risk of type 1 diabetes.METHODS: We established HLA-A*24, DQ and rs9258750 (an HLA-A*24 tagged single-nucleotide polymorphism) genotype, as well as GAD, zinc transporter 8 (ZnT8), insulin, islet antigen-2 (IA-2), and IA-2β autoantibody status in 373 islet cell antibody-positive first-degree relatives participating in the European Nicotinamide Diabetes Intervention Trial.RESULTS: Univariate regression analyses showed that humoral responses to GAD, ZnT8 and insulin were less common in relatives carrying HLA-A*24. The prevalence of GAD and ZnT8 autoantibodies remained negatively associated with HLA-A*24 and rs9258750 after adjusting for age, sex, proband relationship and HLA class II genotype.CONCLUSIONS/INTERPRETATION: HLA-A*24 is associated with attenuated humoral responses in individuals at high risk of type 1 diabetes, and this may reflect a distinct phenotype of rapid beta cell loss.

AB - AIMS/HYPOTHESIS: The rate of progression from islet autoimmunity to clinical type 1 diabetes depends on the rate of beta cell destruction. The HLA-A*24 gene is associated with early diabetes onset, but previous studies have shown attenuated humoral responses to islet antigens in individuals with both recent and long-standing type 1 diabetes carrying HLA-A*24. We aimed to establish whether HLA-A*24 is also associated with attenuated humoral responses in individuals at high risk of type 1 diabetes.METHODS: We established HLA-A*24, DQ and rs9258750 (an HLA-A*24 tagged single-nucleotide polymorphism) genotype, as well as GAD, zinc transporter 8 (ZnT8), insulin, islet antigen-2 (IA-2), and IA-2β autoantibody status in 373 islet cell antibody-positive first-degree relatives participating in the European Nicotinamide Diabetes Intervention Trial.RESULTS: Univariate regression analyses showed that humoral responses to GAD, ZnT8 and insulin were less common in relatives carrying HLA-A*24. The prevalence of GAD and ZnT8 autoantibodies remained negatively associated with HLA-A*24 and rs9258750 after adjusting for age, sex, proband relationship and HLA class II genotype.CONCLUSIONS/INTERPRETATION: HLA-A*24 is associated with attenuated humoral responses in individuals at high risk of type 1 diabetes, and this may reflect a distinct phenotype of rapid beta cell loss.

U2 - 10.1007/s00125-015-3702-9

DO - 10.1007/s00125-015-3702-9

M3 - Article (Academic Journal)

C2 - 26224099

VL - 58

SP - 2284

EP - 2287

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 10

ER -