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

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

Abbreviations: SS, Sjögren's syndrome; MR, muscarinic receptor; ANA, antinuclear antibodies; CHO, Chinese hamster ovary; MAPK, MAP kinase; IVIg, intravenous immunoglobulin.
anti-muscarinic receptor antibodies, sjögren's syndrome, binding assays, cross reactivity, intravenous immunoglobulin
1045-1056
213-222
Schegg, Vanessa
813c1df5-69cb-47bd-a4b0-fcdf909e111c
Vogel, Monique
395638d4-00c0-49b8-903f-0a83b07558ec
Didichenko, Svetlana
4502a3fe-513b-449e-9c62-f68665971ff4
Stadler, Michael B.
c690a717-3c34-431f-b076-2dca3cdb957e
Beleznay, Zsuzsanna
52cf0bd8-0b39-46c8-879c-50003472f228
Gadola, Stephan
ef2fa6cf-2ccc-4fea-a7a5-cc03a9d13ab1
Sengupta, Christine
97cabcd2-037f-46d7-9504-a3eb3a4530bd
Stadler, Beda M.
28ceb08a-b02c-4cae-b7c5-bf202b451a08
Miescher, Sylvia M.
50887dd2-6110-4e2b-bc74-b6a52e0cb452
Schegg, Vanessa
813c1df5-69cb-47bd-a4b0-fcdf909e111c
Vogel, Monique
395638d4-00c0-49b8-903f-0a83b07558ec
Didichenko, Svetlana
4502a3fe-513b-449e-9c62-f68665971ff4
Stadler, Michael B.
c690a717-3c34-431f-b076-2dca3cdb957e
Beleznay, Zsuzsanna
52cf0bd8-0b39-46c8-879c-50003472f228
Gadola, Stephan
ef2fa6cf-2ccc-4fea-a7a5-cc03a9d13ab1
Sengupta, Christine
97cabcd2-037f-46d7-9504-a3eb3a4530bd
Stadler, Beda M.
28ceb08a-b02c-4cae-b7c5-bf202b451a08
Miescher, Sylvia M.
50887dd2-6110-4e2b-bc74-b6a52e0cb452

Schegg, Vanessa, Vogel, Monique, Didichenko, Svetlana, Stadler, Michael B., Beleznay, Zsuzsanna, Gadola, Stephan, Sengupta, Christine, Stadler, Beda M. and Miescher, Sylvia M. (2008) Evidence that anti-muscarinic antibodies in Sjögren's syndrome recognise both M3R and M1R. Biologicals, 36 (4), 213-222. (doi:10.1016/j.biologicals.2007.11.001).

Record type: Article

Abstract

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.

Abbreviations: SS, Sjögren's syndrome; MR, muscarinic receptor; ANA, antinuclear antibodies; CHO, Chinese hamster ovary; MAPK, MAP kinase; IVIg, intravenous immunoglobulin.

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More information

Published date: July 2008
Keywords: anti-muscarinic receptor antibodies, sjögren's syndrome, binding assays, cross reactivity, intravenous immunoglobulin

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Local EPrints ID: 59408
URI: http://eprints.soton.ac.uk/id/eprint/59408
ISSN: 1045-1056
PURE UUID: 8f67f3e1-9916-4719-aceb-e5c4af81d78e

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Date deposited: 17 Sep 2008
Last modified: 15 Mar 2024 11:16

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Contributors

Author: Vanessa Schegg
Author: Monique Vogel
Author: Svetlana Didichenko
Author: Michael B. Stadler
Author: Zsuzsanna Beleznay
Author: Stephan Gadola
Author: Christine Sengupta
Author: Beda M. Stadler
Author: Sylvia M. Miescher

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