RESEARCH - Antimuscarinic antibodies in primary Sjogren's syndrome

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Arthritis Rheum. 2006 Apr;54(4):1165-73.

Antimuscarinic antibodies in primary Sjogren's syndrome reversibly inhibit

the mechanism of fluid secretion by human submandibular salivary acinar

cells.

Dawson LJ, Stanbury J, Venn N, Hasdimir B, SN, PM.

The University of Liverpool, and Aintree Hospitals, Liverpool, UK.

ldawson@...

OBJECTIVE: Sjogren's syndrome (SS) is an autoimmune condition affecting

salivary glands, for which a clearly defined pathogenic autoantibody has yet

to be identified. Autoantibodies that bind to the muscarinic M3 receptors

(M3R), which regulate fluid secretion in salivary glands, have been proposed

in this context. However, there are no previous data that directly show

antisecretory activity. This study was undertaken to investigate and

characterize the antisecretory activity of anti-M3R. METHODS:

Microfluorimetric Ca2+ imaging and patch clamp electrophysiologic techniques

were used to measure the secretagogue-evoked increase in [Ca2+]i and

consequent activation of Ca2+-dependent ion channels in individual mouse and

human submandibular acinar cells. Together, these techniques form a

sensitive bioassay that was used to determine whether IgG isolated from

patients with primary SS and from control subjects has antisecretory

activity. RESULTS: IgG (2 mg/ml) from patients with primary SS reduced the

carbachol-evoked increase in [Ca2+]i in both mouse and human acinar cells by

approximately 50%. IgG from control subjects had no effect on the Ca2+

signal. Furthermore, the inhibitory action of primary SS patient IgG on the

Ca2+ signal was acutely reversible. We repeated our observations using

rabbit serum containing antibodies raised against the second extracellular

loop of M3R and found an identical pattern of acutely reversible inhibition.

Anti-M3R-positive serum had no effect on Ca2+-dependent ion channel

activation evoked by the direct intracellular infusion of inositol

1,4,5-triphosphate.

CONCLUSION: These observations show for the first time that IgG from

patients with primary SS contains autoantibodies capable of damaging saliva

production and contributing to xerostomia. The unusual but not unprecedented

acute reversibility of the effects of anti-M3 autoantibodies is the subject

of further research.

PMID: 16572451

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6572451 & dopt=Abstract

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