Increase of angiotensin II type 1 receptor auto-antibodies in Huntington’s disease

Lee, Dong Hoon; Heidecke, Harald; Schröder, A.; Paul, Friedemann; Wachter, Rolf; Hoffmann, Rainer; Ellrichmann, Gisa; Dragun, Duska; Waschbisch, Anne; Stegbauer, Johannes; Klotz, Peter; Gold, Ralf; Dechend, Ralf; Müller, Dominik N.; Saft, Carsten; Linker, Ralf A.

doi:10.1186/1750-1326-9-49

Cited by 24 publications

(16 citation statements)

References 44 publications

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“…In the first report, autoantibodies directed against gliadin, a protein component of gluten, were observed in 44.2% of HD patients [27]. The second report showed alteration in the titers of an antibody to angiotensin II type 1 receptors (AT1R); this antibody promoting dysfunction of the adaptive immune system [28]. MS patients show increased titers of anti-AT1R in comparison with matching controls.…”

Section: Clinical Features Of Neuroinflammation In Hdmentioning

confidence: 99%

The choreography of neuroinflammation in Huntington's disease

Crotti

Glass

2015

Trends in Immunology

220

162

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Currently, the concept of ‘neuroinflammation’ includes inflammation associated with neurodegenerative diseases, in which there is little or no infiltration of blood-derived immune cells into the brain. The roles of brain-resident and peripheral immune cells in these inflammatory settings are poorly understood, and it is unclear whether neuroinflammation results from immune reaction to neuronal dysfunction/degeneration, and/or represents cell-autonomous phenotypes of dysfunctional immune cells. Here, we review recent studies examining these questions in the context of Huntington’s disease (HD), where mutant Huntingtin (HTT) is expressed in both neurons and glia. Insights into the cellular and molecular mechanisms underlying neuroinflammation in HD may provide a better understanding of inflammation in more complex neurodegenerative disorders, and of the contribution of the neuroinflammatory component to neurodegenerative disease pathogenesis.

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Section: Clinical Features Of Neuroinflammation In Hdmentioning

confidence: 99%

The choreography of neuroinflammation in Huntington's disease

Crotti

Glass

2015

Trends in Immunology

220

162

View full text Add to dashboard Cite

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“…The anti-AT 1 antibody titers correlated with the age of HD onset and disease burden scores and were also linked to smoking and infection. These data suggest a dysfunction of the adaptive immune system in HD, which may be triggered by different stimuli including autoimmune responses, infection, and possibly smoking (Lee et al, 2014).…”

Section: Discussionmentioning

confidence: 87%

Peripheral Levels of Renin-Angiotensin System Components Are Associated With Cognitive Performance in Huntington’s Disease

et al. 2020

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The renin-angiotensin system (RAS) has proven to be involved in the pathophysiology of neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), serving as a potential therapeutic target and a disease burden marker. Studies have associated negative clinical outcomes with the activation of the classical RAS arm composed of the angiotensin-converting enzyme (ACE) and angiotensin (Ang) II, while suggested positive outcomes with the activation of the counter-regulatory RAS arm involving ACE2 and Ang-(1–7). Huntington’s disease (HD) shares many pathological and clinical outcomes with AD and PD, but the evidence of direct involvement of RAS components in the pathophysiology of HD is still limited and needs further investigation. Herein, we investigated peripheral levels of the RAS components Ang II, Ang-(1–7), ACE, and ACE2 in controls, premanifest, and manifest HD gene carriers and their relationship with clinical outcomes. Peripheral blood samples were collected via phlebotomy, and plasma concentrations of RAS components were measured by Enzyme-Linked Immunosorbent Assay. Clinical evaluation included a questionnaire about socio-demographic characteristics, motor, and cognitive assessments. Results showed (1) no significant group differences in plasma concentrations of RAS components; (2) positive correlations between ACE2 and Verbal Fluency Test (VFT) scores; and (3) negative correlations between Ang II and Mini–Mental State Examination scores. These results corroborate the proposed balance between the classical (ACE/Ang II) and the counter-regulatory [ACE2/Ang-(1–7)] arms of the RAS, with the former associated with negative clinical outcomes and the latter with positive effects in HD.

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“…Nonoriginal research (reviews or comments) or animal model studies were excluded. Because AT1-AA was also found in some other diseases such as Graves disease 10 or Huntington disease, 11 we also removed studies without matched controls or with hypertensive patients who have complications to avoid misdirection. All studies were subjected to quality assessment, based on the Newcastle–Ottawa Scale (NOS) with some modifications.…”

Section: Methodsmentioning

confidence: 99%