Sera from Patients with Type 2 Diabetes Contain Agonistic Autoantibodies Against G Protein‐Coupled Receptors

Hempel, Petra; Karczewski, Peter; Kohnert, K.-D.; Raabe, Jan; Lemke, Bernd; Kunze, Rudolf; Bimmler, Marion

doi:10.1111/j.1365-3083.2009.02280.x

Cited by 31 publications

(28 citation statements)

References 9 publications

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“…Increased prevalence of positive autoantibody and T-cell responses are found to target a spectrum of self-antigens, including islet autoantigens but also autoantigens expressed in multiple cell types and tissues (11,49,53,(66)(67)(68). Among these are Golgi SNAP receptor complex member 1 (GOSR1) transcript variant 1, a protein involved in trafficking between the ER and Golgi compartments, phosphogluconate dehydrogenase, and GFAP.…”

Section: Potential Autoantigen Targetsmentioning

confidence: 99%

See 1 more Smart Citation

Are Obesity-Related Insulin Resistance and Type 2 Diabetes Autoimmune Diseases?

et al. 2015

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Obesity and associated insulin resistance predispose individuals to develop chronic metabolic diseases, such as type 2 diabetes and cardiovascular disease. Although these disorders affect a significant proportion of the global population, the underlying mechanisms of disease remain poorly understood. The discovery of elevated tumor necrosis factor-α in adipose tissue as an inducer of obesity-associated insulin resistance marked a new era of understanding that a subclinical inflammatory process underlies the insulin resistance and metabolic dysfunction that precedes type 2 diabetes. Advances in the field identified components of both the innate and adaptive immune response as key players in regulating such inflammatory processes. As antigen specificity is a hallmark of an adaptive immune response, its role in modulating the chronic inflammation that accompanies obesity and type 2 diabetes begs the question of whether insulin resistance and type 2 diabetes can have autoimmune components. In this Perspective, we summarize current data that pertain to the activation and perpetuation of adaptive immune responses during obesity and discuss key missing links and potential mechanisms for obesity-related insulin resistance and type 2 diabetes to be considered as potential autoimmune diseases.

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Section: Potential Autoantigen Targetsmentioning

confidence: 99%

“…For instance, autoantibodies against a modified epitope in ApoB or agonistic autoantibodies against G-protein-coupled receptors have been associated with endothelial dysfunction and vascular complications (66,67). Some autoantibody targets may emerge after bacterial or viral infection.…”

Section: Potential Autoantigen Targetsmentioning

confidence: 99%

Are Obesity-Related Insulin Resistance and Type 2 Diabetes Autoimmune Diseases?

et al. 2015

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“…In addition to age, acquired cardiovascular disorders, such as mid-life hypertension [2], diabetes [3], atrial fibrillation [4], and atherosclerotic disease [5], increase the risk of later development of AD. These risk factors are known to be associated with agonist antibodies to key G protein-coupled receptors (GPCR) of the vasculature and autonomic nervous system, such as alpha 1 adrenoceptors (␣ 1 -AR), angiotensin 2 type 1 receptors (AT1R), beta 1 adrenoceptors (␤ 1 -AR), M2 muscarinic receptors (M 2 -MR), and endothelin-1-type A receptors (ET1A) [6][7][8][9][10]. Anti-GPCR antibodies such as anti-␤ 2 -AR and anti-␣ 1 -AR were recently found to be associated with AD and vascular dementia [11].…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies Toward the Angiotensin 2 Type 1 Receptor: A Novel Autoantibody in Alzheimer’s Disease

Giil

Kristoffersen

Vedeler

et al. 2015

JAD

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Abstract.Background: Autoantibodies with agonist function are described in cardiovascular disorders. Since vascular risk factors are associated with an increased risk for Alzheimer's disease (AD), we investigated a potential association between antibodies to the angiotensin 2 type 1 receptor (anti-AT1R) and AD. Objective: The primary objective of this study was to investigate the association between anti-AT1R and AD. The secondary objective was to investigate the association between clinical or biomarker features of AD and anti-AT1R. Methods: Samples from patients with mild AD participating in a longitudinal study in Western Norway (n = 92, 65 [71%] females, mean age 74.8 [range 50-89]) and age-and gender-matched healthy controls (n = 102) were included. Cerebrospinal fluid (CSF) AD biomarkers were assessed in a subgroup of patients. Patients were examined annually, including Mini-Mental State Examination. ELISA was used to measure anti-AT1R in serum. Non-parametric tests were used for statistical calculations and a p < 0.05 was considered significant. Results: AD patients had significantly higher levels of anti-AT1R compared with healthy controls (10.2 U/mL versus 8.1 U/mL, p = 0.04). This difference was found only in patients without hypertension and diabetes. Anti-AT1R levels correlated with CSF total tau (p = 0.03) and phosphorylated tau (p = 0.03) levels, and inversely with blood pressure in AD (Spearman R −0.277, p = 0.008). Discussion: AD is associated with increased levels of anti-AT1R, and the antibodies correlated with CSF total, and phosphorylated tau levels. Further research is needed to understand the blood pressure response in AD without hypertension and a potential link between tau and anti-AT1R in AD.

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“…The possibly higher responder rate to unspecific IA in DM patients might result from possible additional removal by IA of other AABs which might be directly or indirectly involved in the development and progression of DCM. This hypothesis is suggested by previous observations made by other groups who, in sera from diabetic patients with and without altered heart function, also detected other agonistic AABs against Gprotein-couplet receptors [22,23]. Our observation that in patients with available strain imaging recordings, post-IA strain and strain-rate improvement was higher than LVEF improvement might suggest that strain imaging would be more suited than LVEF for identification of responders to IA and that the prevalence of responders to IA might be higher if in future strain and strain-rate are used instead of LVEF for distinction between responders and nonresponders to IA.…”

Section: Discussionmentioning

confidence: 55%

“…Agonistic AABs against G-protein-couplet receptors, including b 1 -AABs, were detected in diabetic patient sera with and without altered heart function and the pathogenic impact of certain AABs such as a 1 -AABs was already investigated [13,22,23] Nevertheless, the role of b 1 -AABs in DM-associated DCM and the impact of b 1 -AAB removal in that special constellation, where diabetes-associated metabolic effects plus myocardial microvascular lesions might diminish the pathogenetical role of b 1 -AABs for HF development, are barely known.…”

Section: Introductionmentioning

confidence: 99%