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APOE isotype-dependent regulation of IgG and IgA levels against different IAPP epitopes

Pocevičiūtė, Dovilė LU orcid ; Roth, Bodil LU ; Olofsson, Anders LU ; Hansson, Oskar LU orcid and Wennström, Malin LU (2026) In Immunology Letters 279.
Abstract

The efficient clearance of IAPP oligomers (IAPPo) by autoantibodies is crucial as increased plasma levels of IAPPo can induce microvascular alterations and Alzheimer's disease (AD)-characteristic amyloid-β deposition in the brain. We have recently demonstrated that plasma immunoglobulin (Ig) A levels against IAPPo, but not IgG, are reduced in an Apolipoprotein E (APOE) ε4 allele dose-dependent manner. In this study, we aimed to investigate if this APOE genotype-dependent impact can be explained by differences in IAPP epitope recognition by IgA and IgG. We found that the specificity for IAPP epitopes does not differ between IgG and IgA autoantibodies and that IgG and IgA autoantibodies are directed foremost against the C-terminus of the... (More)

The efficient clearance of IAPP oligomers (IAPPo) by autoantibodies is crucial as increased plasma levels of IAPPo can induce microvascular alterations and Alzheimer's disease (AD)-characteristic amyloid-β deposition in the brain. We have recently demonstrated that plasma immunoglobulin (Ig) A levels against IAPPo, but not IgG, are reduced in an Apolipoprotein E (APOE) ε4 allele dose-dependent manner. In this study, we aimed to investigate if this APOE genotype-dependent impact can be explained by differences in IAPP epitope recognition by IgA and IgG. We found that the specificity for IAPP epitopes does not differ between IgG and IgA autoantibodies and that IgG and IgA autoantibodies are directed foremost against the C-terminus of the IAPP. However, IgG autoantibody levels against the N-terminus and midportion of IAPP increased significantly in AD patients with APOE44 compared to controls with APOE33, while the opposite was seen in IgA autoantibody levels. We propose that the IgG and IgA levels against different IAPP epitopes are APOE isotype-dependent, possibly due to differences in cytokine profile between various APOE genotypes or the need for different effector functions of IgG or IgA.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Immunoglobulin G/immunology, Immunoglobulin A/blood, Epitopes/immunology, Alzheimer Disease/immunology, Autoantibodies/immunology, Apolipoproteins E/genetics, Genotype, Female, Islet Amyloid Polypeptide/immunology, Male
in
Immunology Letters
volume
279
article number
107152
publisher
Elsevier
external identifiers
  • pmid:41698553
  • scopus:105030367507
ISSN
0165-2478
DOI
10.1016/j.imlet.2026.107152
language
English
LU publication?
yes
additional info
Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.
id
4f8d8388-3039-47ba-b7e3-14d3e9b9c283
date added to LUP
2026-08-25 09:29:53
date last changed
2026-09-09 04:48:49
@article{4f8d8388-3039-47ba-b7e3-14d3e9b9c283,
  abstract     = {{<p>The efficient clearance of IAPP oligomers (IAPPo) by autoantibodies is crucial as increased plasma levels of IAPPo can induce microvascular alterations and Alzheimer's disease (AD)-characteristic amyloid-β deposition in the brain. We have recently demonstrated that plasma immunoglobulin (Ig) A levels against IAPPo, but not IgG, are reduced in an Apolipoprotein E (APOE) ε4 allele dose-dependent manner. In this study, we aimed to investigate if this APOE genotype-dependent impact can be explained by differences in IAPP epitope recognition by IgA and IgG. We found that the specificity for IAPP epitopes does not differ between IgG and IgA autoantibodies and that IgG and IgA autoantibodies are directed foremost against the C-terminus of the IAPP. However, IgG autoantibody levels against the N-terminus and midportion of IAPP increased significantly in AD patients with APOE44 compared to controls with APOE33, while the opposite was seen in IgA autoantibody levels. We propose that the IgG and IgA levels against different IAPP epitopes are APOE isotype-dependent, possibly due to differences in cytokine profile between various APOE genotypes or the need for different effector functions of IgG or IgA.</p>}},
  author       = {{Pocevičiūtė, Dovilė and Roth, Bodil and Olofsson, Anders and Hansson, Oskar and Wennström, Malin}},
  issn         = {{0165-2478}},
  keywords     = {{Humans; Immunoglobulin G/immunology; Immunoglobulin A/blood; Epitopes/immunology; Alzheimer Disease/immunology; Autoantibodies/immunology; Apolipoproteins E/genetics; Genotype; Female; Islet Amyloid Polypeptide/immunology; Male}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Immunology Letters}},
  title        = {{APOE isotype-dependent regulation of IgG and IgA levels against different IAPP epitopes}},
  url          = {{http://dx.doi.org/10.1016/j.imlet.2026.107152}},
  doi          = {{10.1016/j.imlet.2026.107152}},
  volume       = {{279}},
  year         = {{2026}},
}