Autoantibodies Against Methylglyoxal-Modified Apolipoprotein B100 and ApoB100 Peptide Are Associated With Less Coronary Artery Atherosclerosis and Retinopathy in Long-Term Type 1 Diabetes.

Abstract

OBJECTIVE:

Methylglyoxal (MGO), a reactive aldehyde forming advanced glycation end products (AGEs), is increased in diabetes and recognized by the immune system, resulting in anti-AGE-specific autoantibodies. The association of these immune responses with macro- and microvascular complications in type 1 diabetes remains unclarified. We investigated associations between MGO-modified apolipoprotein B100 (apoB100) and apoB100 peptide 5 (MGO-p5) autoantibodies and coronary atherosclerosis and retinopathy in type 1 diabetes.

RESEARCH DESIGN AND METHODS:

IgM and IgG against MGO-apoB100 and MGO-p5 were measured by ELISA in plasma from 103 subjects with type 1 diabetes and 63 control subjects (Dialong study) and in a replication cohort of 27 subjects with type 1 diabetes (Oslo study). Coronary atherosclerosis was assessed by computed tomography coronary angiography or intravascular ultrasound. Retinopathy was classified by retinal photos.

RESULTS:

MGO-apoB100 IgM and MGO-p5 IgM levels were higher in subjects with diabetes with no coronary artery stenosis compared with subjects with significant stenosis (median [interquartile range]: 96.2 arbitrary units [AU] [71-126.8] vs. 54 AU [36.1-85.4], P = 0.003 for MGO-apoB100; and 77.4 AU [58-106] vs. 36.9 AU [28.9-57.4], P = 0.005 for MGO-p5). MGO-apoB100 IgM and MGO-p5 IgM were associated with less severe coronary stenosis after adjusting for confounders (odds ratio 0.2 [95% CI 0.05-0.6], P = 0.01; and 0.22 [0.06-0.75], P = 0.02). The inverse association of MGO-p5 IgM and coronary stenosis was confirmed in the replication cohort. Subjects with proliferative retinopathy had significantly lower MGO-apoB100 IgM and MGO-p5 IgM than those with background retinopathy.

CONCLUSIONS:

Autoantibodies against AGE-modified apoB100 are inversely associated with coronary atherosclerosis and proliferative retinopathy, suggesting vascular protective effects of these autoantibodies in type 1 diabetes.

• Authors: Kari Anne Sveen, Kristine Bech Holte, Mona Svanteson, Kristian F Hanssen, Jan Nilsson, Eva Bengtsson, Tore Julsrud Berg
• Journal: Diabetes care (Diabetes Care) Vol. 44 Issue 6 Pg. 1402-1409 (06 2021) ISSN: 1935-5548 [Electronic] United States
• PMID: 33858856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by the American Diabetes Association.

Chemical References

• Apolipoprotein B-100
• Autoantibodies
• Peptides
• Pyruvaldehyde

Topics

• Apolipoprotein B-100 (immunology)
• Atherosclerosis
• Autoantibodies
• Coronary Artery Disease
• Diabetes Mellitus, Type 1
• Diabetic Retinopathy
• Humans
• Peptides
• Pyruvaldehyde