Article Text

PDF
A3.9 IGG subclasses of autoantibodies directed against the angiotensin receptor type 1 and the endothelin receptor type a and their clinical relevance
  1. J. Günther,
  2. A Kill,
  3. M. Becker,
  4. E Siegert,
  5. H Heidecke,
  6. G Riemekasten
  1. University Hospital Charité, Department of Rheumatology and Clinical Immunology, Berlin; German Rheumatism Research Center (DRFZ), a Leibniz Institute, Berlin

Abstract

Background and Objectives IgG4-related diseases are often characterised by a generalised inflammatory fibrosis which is also present in patients suffering from systemic sclerosis (SSc). Recent findings indicate the importance of autoantibodies (Aabs) against the angiotensin II type-1 receptor (AT1R) and the endothelin type-A receptor (ETAR) in the pathogenesis of SSc. Therefore, we analysed the levels of anti-AT1R/ETAR IgG sublasses in patients with SSc to determine a possible role of IgG subclasses as markers for disease manifestations in SSc.

Material and Methods Sera from 91 SSc patients, 59 patients suffering from systemic lupus erythematosus (SLE), and from 199 healthy donors were analysed for the levels of anti-AT1R and anti-ETAR Aabs as well as for the different anti-AT1R and anti-ETAR IgG subclasses by ELISA. The results were associated with clinical manifestations using Mann-Whitney test and correlated with the time since onset of disease manifestations by Spearman correlation test.

Results IgG3 followed by IgG1 was found to show highest anti-AT1R/ETAR Aab levels in all analysed groups, in which SSc patients as well as SLE patients had higher IgG1 and IgG3 anti-AT1R/ETAR Aab levels as compared to healthy donors. Comparing SLE and SSc patients IgG1 and IgG3 showed slightly higher anti-AT1R/ETAR Aab levels in SLE.

Within the SSc group patients with diffuse SSc had higher anti-AT1R/ETAR IgG3 levels as compared to those with limited disease or overlap forms.

Correlation analysis with SSc-related clinical manifestations revealed that levels of anti- AT1R/ETAR IgG3 negatively correlated with time since onset of Raynaud’s phenomenon, and with time since first detection of PAH. Of note, there were negative correlations between levels of anti-AT1R/ETAR IgG3 levels and diffusion capacity for carbon monoxide (DLCO) as well as between anti-AT1R/ETAR-IgG3 levels and forced vital capacity (FVC) values (p = 0.02/0.07 and p = 0.01/0.03, respectively).

Conclusion Interestingly, not IgG4 but IgG3 showed highest anti-AT1R/ETAR Aab levels when compared to other IgG subclasses. However, in SSc patients, anti-AT1R/ETAR IgG3 levels are strongly correlated to certain disease manifestations, whereby high anti-AT1R/ETAR IgG3 levels are associated with low DLCO and FVC indicating deterioration of lung function. According to these findings high anti-AT1R/ETAR IgG3 levels could predict for lung function deterioration and represent a new marker for SSc complications.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.