ArticleGastroenterology2012
Effects of scleroderma antibodies and pooled human immunoglobulin on anal sphincter and colonic smooth muscle function.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Esophageal peristalsis in health and disease: mechanistic insights.Physiological reviews · 2026Review
- Expert recommendations for the management of fecal incontinence in systemic sclerosis: A report from the World Scleroderma Foundation (WSF) Gastrointestinal "Ad hoc committee".Journal of scleroderma and related disorders · 2026Article
- Cellular Players in Gastrointestinal Involvement of Systemic Sclerosis: Insights into Pathogenesis.Cells · 2025Review
- Anti-cytolethal distending toxin antibodies in systemic sclerosis: associations with gastrointestinal disease and immune dysregulation.Rheumatology (Oxford, England) · 2025Article
- Anti-muscarinic 3 antibodies associate with a severe clinical phenotype in patients with systemic sclerosis.Rheumatology (Oxford, England) · 2025Article
- Systemic sclerosis and anorectal dysfunction: The Leeds experience.Journal of scleroderma and related disorders · 2024Article
- Managing gastrointestinal manifestations in systemic sclerosis, a mechanistic approach.Expert review of clinical immunology · 2024Review
- Autoantibodies Targeting G-Protein-Coupled Receptors: Pathogenetic, Clinical and Therapeutic Implications in Systemic Sclerosis.International journal of molecular sciences · 2024Review
- Anti-Gephyrin Antibodies: A Novel Specificity in Patients With Systemic Sclerosis and Lower Bowel Dysfunction.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Subcutaneous immunoglobulin therapy for refractory skin thickening in rapidly progressive systemic sclerosis: A case report and literature review.Journal of scleroderma and related disorders · 2023Review
- Systemic sclerosis gastrointestinal dysmotility: risk factors, pathophysiology, diagnosis and management.Nature reviews. Rheumatology · 2023Review
- When natural antibodies become pathogenic: autoantibodies targeted against G protein-coupled receptors in the pathogenesis of systemic sclerosis.Frontiers in immunology · 2023Review
- Treatment of Severe Swallowing Dysfunction in Systemic Sclerosis with IVIG: Role of Antimuscarinic Antibodies.Journal of clinical medicine · 2022Article
- Fecal microbiome in systemic sclerosis, in search for the best candidate for microbiota-targeted therapy for small intestinal bacterial overgrowth control.Journal of scleroderma and related disorders · 2022Article
- Management of scleroderma gastrointestinal disease: Lights and shadows.Journal of scleroderma and related disorders · 2022Review
- Putative functional pathogenic autoantibodies in systemic sclerosis.European journal of rheumatology · 2020Review
- Pathogenic roles of autoantibodies in systemic sclerosis: Current understandings in pathogenesis.Journal of scleroderma and related disorders · 2020Review
- Small intestinal bacterial overgrowth in systemic sclerosis.Journal of scleroderma and related disorders · 2020Review
- BDNF augments rat internal anal sphincter smooth muscle tone via RhoA/ROCK signaling and nonadrenergic noncholinergic relaxation via increased NO release.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Gastrointestinal Involvement in Systemic Sclerosis: An Update.Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsPatients with systemic sclerosis (SSc) have impairments in gastrointestinal smooth muscle function. The disorder has been associated with circulating antibodies to cholinergic muscarinic the type-3 receptor (M(3)-R). We investigated whether it is possible to neutralize these antibodies with pooled human IgGs (pooledhIgG).
methodsWe studied the effects of IgGs purified from patients with SSc (SScIgGs) on cholinergic nerve stimulation in rat colon tissues. We also examined the effects of SScIgGs on M(3)-R activation by bethanechol (BeCh), M(3)-R occupancy, and receptor binding using immunofluorescence, immunoblot, and enzyme-linked immunosorbent analyses of human internal anal sphincter (IAS) smooth muscle cells, before and after administration of pooledhIgG. Functional displacement of M(3)-R occupancy by the SScIgGs was compared with that of other IgGs during the sustained phase of BeCh-induced contraction of intact smooth muscles from rats.
resultsSScIgG significantly attenuated neurally mediated contraction and acetylcholine release in rat colon as well as BeCh-induced sustained contraction of the IAS smooth muscle. In immunofluorescence analysis, SScIgG co-localized with M(3)-R. In immunoblot and enzyme-linked immunosorbent analyses, M(3)-R loop-2 peptide and human IAS SMC membrane lysates bound significant amounts of SScIgG, compared with IgGs from healthy individuals and pooledhIgG. Binding was attenuated significantly by application of pooledhIgG, which by itself had no significant effect. Incubation of samples with pooledhIgG, or mixing pooledhIgG with SScIgG before administration to tissues, significantly reduced binding of SScIgG, indicating that pooledhIgG prevents SScIgG blockade of M(3)-R.
conclusionsIn studies of rat and human tissues, pooled human IgG prevent and reverses the cholinergic dysfunction associated with the progressive gastrointestinal manifestations of SSc by neutralizing functional M(3)-R antibodies present in the circulation of patients with SSc.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.