Evidence that anti-muscarinic antibodies in Sjögren's syndrome recognise both M3R and M1R

Schegg, Vanessa; Vogel, Monique; Didichenko, Svetlana; Stadler, Michael B; Beleznay, Zsuzsanna; Gadola, Stephan; Sengupta, Christine; Stadler, Beda M; Miescher, Sylvia M (2008). Evidence that anti-muscarinic antibodies in Sjögren's syndrome recognise both M3R and M1R. Biologicals, 36(4), pp. 213-22. London: Elsevier 10.1016/j.biologicals.2007.11.001

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Inhibitory anti-muscarinic receptor type 3 (M3R) antibodies may contribute to the pathogenesis of Sjögren's syndrome (SS), and putative anti-M3R blocking antibodies in intravenous immunoglobulin (IVIg) have been suggested as a rationale for treatment with IVIg. We investigated the presence of subtype-specific anti-MR autoantibodies in healthy donor and SS sera using MR-transfected whole-cell binding assays as well as M1R and M3R peptide ELISAs. Control antibodies against the second extracellular loop of the M3R, a suggested target epitope, were induced in rabbits and found to be cross-reactive on the peptides M3R and M1R. The rabbit antibodies had neither an agonistic nor an antagonistic effect on M3R-dependent ERK1/2 signalling. Only one primary SS (out of 5 primary SS, 2 secondary SS and 5 control sera) reacted strongly with M3R transfected cells. The same SS serum also reacted strongly with M1R and M2R transfectants, as well as M1R and two different M3R peptides. Strong binding to M1R and low-level activities against M3R peptides were observed both in SS and control sera. IVIg showed a strong reactivity against all three peptides, especially M1R. Our results indicate that certain SS individuals may have antibodies against M1R, M2R and M3R. Our results also suggest that neither the linear M3R peptide nor M3R transfectants represent suitable tools for discrimination of pathogenic from natural autoantibodies in SS.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology (discontinued)

UniBE Contributor:

Vogel, Monique; Beleznay, Zsuzsanna and Stadler, Beda Martin

ISSN:

1045-1056

ISBN:

18249005

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:04

Last Modified:

04 May 2014 23:20

Publisher DOI:

10.1016/j.biologicals.2007.11.001

PubMed ID:

18249005

Web of Science ID:

000257972200001

URI:

https://boris.unibe.ch/id/eprint/27952 (FactScience: 114408)

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