Increased levels of anti-BSA antibodies in children with Down syndrome

Sian L Grace; Georgina L Mortimer; Aizhan Kozhakhmetova; Jamie Leveret; Richard Newton; Koit Reimand; Julian P H Shield; Raivo Uibo; Alistair J K Williams; Kathleen M Gillespie

doi:10.3389/fendo.2023.1056925

Increased levels of anti-BSA antibodies in children with Down syndrome

Sian L Grace, Georgina L Mortimer, Aizhan Kozhakhmetova, Jamie Leveret, Richard Newton, Koit Reimand, Julian P H Shield, Raivo Uibo, Alistair J K Williams, Kathleen M Gillespie

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

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Abstract

INTRODUCTION: Autoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125I-labelled insulin require competition to overcome cross reactivity with antibodies to the cow's milk protein, bovine serum albumin (BSA). 125I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls.

METHODS: Samples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Bart's Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP).

RESULTS: Overall, levels of anti-BSA antibodies were increased in those with DS compared with controls (p<0.0001) but this was not HLA associated.

CONCLUSION: Increased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity.

Original language	English
Article number	1056925
Number of pages	7
Journal	Frontiers in Endocrinology
Volume	14
DOIs	https://doi.org/10.3389/fendo.2023.1056925
Publication status	Published - 3 Feb 2023

Bibliographical note

Funding Information:
This work was funded by grants to KG from the Diabetes Research and Wellness Foundation and the Lejeune Foundation (Project #1909). Control samples were collected as part of the Barts Oxford study of type 1 diabetes funded by Diabetes UK Grant Reference 14/0004869. JPHS receives support for research through the NIHR Biomedical Research Centre funding scheme. Acknowledgments

Publisher Copyright:
Copyright © 2023 Grace, Mortimer, Kozhakhmetova, Leveret, Newton, Reimand, Shield, Uibo, Williams and Gillespie.

Keywords

Animals
Female
Cattle
Child
Humans
Male
Serum Albumin, Bovine
Down Syndrome
Diabetes Mellitus, Type 1/genetics
Autoantibodies
Insulin

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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@article{160baec819ac49ad90de039e213598ee,

title = "Increased levels of anti-BSA antibodies in children with Down syndrome",

abstract = "INTRODUCTION: Autoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125I-labelled insulin require competition to overcome cross reactivity with antibodies to the cow's milk protein, bovine serum albumin (BSA). 125I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls.METHODS: Samples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Bart's Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP).RESULTS: Overall, levels of anti-BSA antibodies were increased in those with DS compared with controls (p<0.0001) but this was not HLA associated.CONCLUSION: Increased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity.",

keywords = "Animals, Female, Cattle, Child, Humans, Male, Serum Albumin, Bovine, Down Syndrome, Diabetes Mellitus, Type 1/genetics, Autoantibodies, Insulin",

author = "Grace, {Sian L} and Mortimer, {Georgina L} and Aizhan Kozhakhmetova and Jamie Leveret and Richard Newton and Koit Reimand and Shield, {Julian P H} and Raivo Uibo and Williams, {Alistair J K} and Gillespie, {Kathleen M}",

note = "Funding Information: This work was funded by grants to KG from the Diabetes Research and Wellness Foundation and the Lejeune Foundation (Project #1909). Control samples were collected as part of the Barts Oxford study of type 1 diabetes funded by Diabetes UK Grant Reference 14/0004869. JPHS receives support for research through the NIHR Biomedical Research Centre funding scheme. Acknowledgments Publisher Copyright: Copyright {\textcopyright} 2023 Grace, Mortimer, Kozhakhmetova, Leveret, Newton, Reimand, Shield, Uibo, Williams and Gillespie.",

year = "2023",

month = feb,

day = "3",

doi = "10.3389/fendo.2023.1056925",

language = "English",

volume = "14",

journal = "Frontiers in Endocrinology",

issn = "1664-2392",

publisher = "Frontiers Media S.A.",

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TY - JOUR

T1 - Increased levels of anti-BSA antibodies in children with Down syndrome

AU - Grace, Sian L

AU - Mortimer, Georgina L

AU - Kozhakhmetova, Aizhan

AU - Leveret, Jamie

AU - Newton, Richard

AU - Reimand, Koit

AU - Shield, Julian P H

AU - Uibo, Raivo

AU - Williams, Alistair J K

AU - Gillespie, Kathleen M

N1 - Funding Information: This work was funded by grants to KG from the Diabetes Research and Wellness Foundation and the Lejeune Foundation (Project #1909). Control samples were collected as part of the Barts Oxford study of type 1 diabetes funded by Diabetes UK Grant Reference 14/0004869. JPHS receives support for research through the NIHR Biomedical Research Centre funding scheme. Acknowledgments Publisher Copyright: Copyright © 2023 Grace, Mortimer, Kozhakhmetova, Leveret, Newton, Reimand, Shield, Uibo, Williams and Gillespie.

PY - 2023/2/3

Y1 - 2023/2/3

N2 - INTRODUCTION: Autoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125I-labelled insulin require competition to overcome cross reactivity with antibodies to the cow's milk protein, bovine serum albumin (BSA). 125I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls.METHODS: Samples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Bart's Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP).RESULTS: Overall, levels of anti-BSA antibodies were increased in those with DS compared with controls (p<0.0001) but this was not HLA associated.CONCLUSION: Increased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity.

AB - INTRODUCTION: Autoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125I-labelled insulin require competition to overcome cross reactivity with antibodies to the cow's milk protein, bovine serum albumin (BSA). 125I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls.METHODS: Samples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Bart's Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP).RESULTS: Overall, levels of anti-BSA antibodies were increased in those with DS compared with controls (p<0.0001) but this was not HLA associated.CONCLUSION: Increased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity.

KW - Animals

KW - Female

KW - Cattle

KW - Child

KW - Humans

KW - Male

KW - Serum Albumin, Bovine

KW - Down Syndrome

KW - Diabetes Mellitus, Type 1/genetics

KW - Autoantibodies

KW - Insulin

U2 - 10.3389/fendo.2023.1056925

DO - 10.3389/fendo.2023.1056925

M3 - Article (Academic Journal)

C2 - 36817608

SN - 1664-2392

VL - 14

JO - Frontiers in Endocrinology

JF - Frontiers in Endocrinology

M1 - 1056925

ER -

Increased levels of anti-BSA antibodies in children with Down syndrome

Abstract

Bibliographical note

Keywords

UN SDGs

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