Immunoglobulins G modulate endothelial function and affect insulin sensitivity in humans.
Adolescent
Biomarkers
/ blood
Blood Glucose
/ drug effects
Brachial Artery
/ drug effects
Case-Control Studies
Cells, Cultured
Common Variable Immunodeficiency
/ blood
Endothelium, Vascular
/ drug effects
Female
Humans
Immunoglobulin G
/ administration & dosage
Immunoglobulins, Intravenous
/ administration & dosage
Infusions, Intravenous
Insulin
/ blood
Insulin Resistance
Male
Nitric Oxide
/ metabolism
Time Factors
Treatment Outcome
Vasodilation
/ drug effects
Young Adult
Atherosclerosis
Endothelial function
Flow mediated dilation
Immunoglobulins
Insulin resistance
Journal
Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474
Informations de publication
Date de publication:
30 10 2020
30 10 2020
Historique:
received:
01
02
2020
revised:
12
06
2020
accepted:
01
07
2020
pubmed:
19
8
2020
medline:
15
12
2020
entrez:
19
8
2020
Statut:
ppublish
Résumé
Data from animals suggest that immunoglobulins G (IgG) play a mechanistic role in atherosclerosis and diabetes through endothelial dysfunction and insulin resistance. Patients with common variable immunodeficiency (CVID), who have low circulating levels of IgG and are treated with intravenous polyclonal IgG (IVIgG), may provide an ideal model to clarify whether circulating IgG modulate endothelial function and affect insulin sensitivity in humans. We studied 24 patients with CVID and 17 matched healthy controls (HC). Endothelial function was evaluated as flow mediated dilation (FMD) of the brachial artery at baseline and 1, 7, 14, and 21 days after IVIgG infusion in the CVID patients. We measured also plasma glucose, insulin, and calculated the HOMA-IR index. We also investigated the role of human IgG on the production of Nitric Oxide (NO) in vitro in Human Coronary Artery Endothelial Cells (HCAEC). Compared to HC, FMD of CVID patients was significantly impaired at baseline (9.4 ± 0.9 and 7.6 ± 0.6% respectively, p < 0.05) but rose above normal levels 1 and 7 days after IVIgG infusion to return at baseline at 14 and 21 days. Serum insulin concentration and HOMA-IR index dropped by 50% in CVID patients after IVIgG (p < 0.002 vs. baseline). In vitro IgG stimulated NO production in HCAEC. Reduced IgG levels are associated with endothelial dysfunction and IVIgG stimulates endothelial function directly while improving insulin sensitivity. The current findings may suggest an anti-atherogenic role of human IgG.
Sections du résumé
BACKGROUND AND AIMS
Data from animals suggest that immunoglobulins G (IgG) play a mechanistic role in atherosclerosis and diabetes through endothelial dysfunction and insulin resistance. Patients with common variable immunodeficiency (CVID), who have low circulating levels of IgG and are treated with intravenous polyclonal IgG (IVIgG), may provide an ideal model to clarify whether circulating IgG modulate endothelial function and affect insulin sensitivity in humans.
METHODS AND RESULTS
We studied 24 patients with CVID and 17 matched healthy controls (HC). Endothelial function was evaluated as flow mediated dilation (FMD) of the brachial artery at baseline and 1, 7, 14, and 21 days after IVIgG infusion in the CVID patients. We measured also plasma glucose, insulin, and calculated the HOMA-IR index. We also investigated the role of human IgG on the production of Nitric Oxide (NO) in vitro in Human Coronary Artery Endothelial Cells (HCAEC). Compared to HC, FMD of CVID patients was significantly impaired at baseline (9.4 ± 0.9 and 7.6 ± 0.6% respectively, p < 0.05) but rose above normal levels 1 and 7 days after IVIgG infusion to return at baseline at 14 and 21 days. Serum insulin concentration and HOMA-IR index dropped by 50% in CVID patients after IVIgG (p < 0.002 vs. baseline). In vitro IgG stimulated NO production in HCAEC.
CONCLUSIONS
Reduced IgG levels are associated with endothelial dysfunction and IVIgG stimulates endothelial function directly while improving insulin sensitivity. The current findings may suggest an anti-atherogenic role of human IgG.
Identifiants
pubmed: 32807637
pii: S0939-4753(20)30273-8
doi: 10.1016/j.numecd.2020.07.001
pii:
doi:
Substances chimiques
Biomarkers
0
Blood Glucose
0
Immunoglobulin G
0
Immunoglobulins, Intravenous
0
Insulin
0
Nitric Oxide
31C4KY9ESH
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2085-2092Informations de copyright
Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no conflict of interest to disclose.