Anti-M3 muscarinic cholinergic autoantibodies from patients with primary Sjögren's syndrome trigger production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E2 (PGE2) from the submandibular glands

Reina, Silvia; Sterin‐Borda, Leonor; Passafaro, Daniela; Borda, Enri

doi:10.1016/j.archoralbio.2010.08.017

Cited by 22 publications

(18 citation statements)

References 24 publications

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“…Although an association does not equate to causal relationship, it is tempting to speculate that autonomic dysfunction may play a key role in PSS pathogenesis. It is noteworthy that antibodies against muscarinic receptor have been implicated in PSS pathogenesis 33–39. Therefore, investigating the relationship between such antibodies and autonomic dysfunction in PSS is warranted.…”

Section: Discussionmentioning

confidence: 99%

Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjögren's syndrome

et al. 2012

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ObjectivesTo determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS.MethodsMulticentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS). The data were compared with an age- and sex-matched cohort of 317 community controls. The relationships between symptoms of dysautonomia and various clinical features of PSS were analysed using regression analysis.ResultsCOMPASS scores were significantly higher in patients with PSS than in age- and sex-matched community controls (median (IQR) 35.5 (20.9–46.0) vs 14.8 (4.4–30.2), p<0.0001). Nearly 55% of patients (vs 20% of community controls, p<0.0001) had a COMPASS score >32.5, a cut-off value indicative of autonomic dysfunction. Furthermore, the COMPASS total score correlated independently with EULAR Sjögren's Syndrome Patient Reported Index (a composite measure of the overall burden of symptoms experienced by patients with PSS) (β=0.38, p<0.001) and disease activity measured using the EULAR Sjögren's Syndrome Disease Activity Index (β=0.13, p<0.009).ConclusionsAutonomic symptoms are common among patients with PSS and may contribute to the overall burden of symptoms and link with systemic disease activity.

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Section: Discussionmentioning

confidence: 99%

Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjögren's syndrome

et al. 2012

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“…Antibodies may also have a role in the pathogenesis of dry mouth by Na + /K + -ATPase inhibition and the net K + efflux stimulation of the salivary gland in response to the authentic agonist pilocarpine, decreasing salivary fluid production. The same group demonstrated serum IgG from Sjögren’s patients, interact with the second extracellular loop of human glandular M3R, triggering the production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E2 (75). Thus, Borda and colleagues propose that PGE2 and MMP-3 are generated by autoantibody activation of COX-2.…”

Section: Anti-muscarinic Receptor Autoantibodiesmentioning

confidence: 99%

Autoantibodies in Sjögren’s Syndrome

Fayyaz

Kurien

Scofield

2016

Rheumatic Disease Clinics of North America

165

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Our purpose was to compile information on antibodies in Sjögren’s syndrome, focusing more on clinical manifestations associated with anti-Ro/SSA and anti-La/SSB antibodies and studies regarding novel antibodies. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading Sjogren’s in combination with antibodies and congenital heart block (CHB). Almost half of asymptomatic mothers giving birth to children with CHB ultimately develop Sjögren’s. We have discussed studies concerning the presence of antibodies predating clinical manifestations of disease. We have considered, in addition to anti-Ro/SSA and anti-La/SSB, anti-centromere antibody (ACA), anti-mitochondrial antibody (AMA) and many novel autoantibodies that have been analyzed in the literature. Studies in the future are required to ascertain the pathogenic mechanisms associated with these antibodies and the specific clinical manifestation related to new autoantibodies.

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“…In general, COX-1 and cPGEs are constitutively expressed in almost all tissues and have haemostatic effects, whereas COX-2 and mPGEs are inducible enzymes that are expressed in response to inflammation [73]. PGE 2 has been shown to be part of the signalling events involved in M 3 mAChR activation [49,71,74].…”

Section: Action Of Anti-muscarinic Acetylcholine Receptors Antibodiesmentioning

confidence: 99%

“…The normal IgG fraction purified by affinity column chromatography gave a negative result (0.30 ± 0.03). ELISA was performed as described previously [74].…”

Section: Purification Of Human Iggmentioning

confidence: 99%

Autoantibodies against Muscarinic Acetylcholine Receptor on Exocrine Glands in Sjögren Syndrome

Reina

Borda²

2014

Dentistry

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These investigations demonstrate that serum antibodies against muscarinic acetylcholine receptors (mAChR) in primary Sjögren syndrome (pSS) and associated Sjögren syndrome (aSS) bind and activate both cholinergic receptors of M 3 in salivary gland and M 1 in neonatal myocardium and in the cerebral frontal cortex area subtypes; triggering the production of the second messengers and proinflammatory mediators related to mAChR activation. In this way the cholinergic autoantibodies damages these receptors, which thus starts acting as an antigen. On this basis M 3 and M 1 mAChR IgG can be considered new markers of pSS/aSS allowing the differentiation between dry eye and mouth of autoimmune and non-autoimmune nature. Given that cholinergic autoantibodies also deregulate the parasympathetic system of the target organs, they can also be seen as a new factor contributing to the etiopathology of the syndrome.

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Anti-M3 muscarinic cholinergic autoantibodies from patients with primary Sjögren's syndrome trigger production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E2 (PGE2) from the submandibular glands

Cited by 22 publications

References 24 publications

Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjögren's syndrome

Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjögren's syndrome

Autoantibodies in Sjögren’s Syndrome

Autoantibodies against Muscarinic Acetylcholine Receptor on Exocrine Glands in Sjögren Syndrome

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