ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2009
Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04630782 (Precision Medicine in Systemic Sclerosis Gastrointestinal Disease), which is not on this map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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.
Precision Medicine in Systemic Sclerosis Gastrointestinal Disease: Evaluating Imaging and Stool Biomarkers for Differentiating Disease Stages and Treatment Responses
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Rapid improvement of systemic sclerosis-associated intestinal pseudo-obstruction with intravenous immunoglobulin administration.Rheumatology (Oxford, England) · 2023Pooled it
- Gastrointestinal Disorders in Scleroderma.Gastroenterology · 2026Review
- Cellular Players in Gastrointestinal Involvement of Systemic Sclerosis: Insights into Pathogenesis.Cells · 2025Review
- Anti-muscarinic 3 antibodies associate with a severe clinical phenotype in patients with systemic sclerosis.Rheumatology (Oxford, England) · 2025Article
- Associations between functional autoantibodies targeting GPCRs, antinuclear antibodies, and inflammatory cytokines TNF-α: a cross-sectional study of 19,810 individuals.Frontiers in immunology · 2025Article
- 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
- Systemic sclerosis gastrointestinal dysmotility: risk factors, pathophysiology, diagnosis and management.Nature reviews. Rheumatology · 2023Review
- Urinary incontinence in systemic sclerosis: a prospective multicentre cohort study.Rheumatology international · 2022Observational
- Evidence for the presence and release of BDNF in the neuronal and non-neuronal structures of the internal anal sphincter.Neurogastroenterology and motility · 2022Article
- Targeting Systemic Sclerosis from Pathogenic Mechanisms to Clinical Manifestations: Why IL-6?Biomedicines · 2022Review
- Pathogenetic Aspects of Systemic Sclerosis: A View Through the Prism of B Cells.Frontiers in immunology · 2022Review
- Anti-vinculin antibodies in scleroderma (SSc): a potential link between autoimmunity and gastrointestinal system involvement in two SSc cohorts.Clinical rheumatology · 2021Article
- Intestinal hypomotility in systemic sclerosis: a histological study into the sequence of events.Clinical rheumatology · 2021Article
- Potential Role for Combined Subtype-Selective Targeting of MFrontiers in pharmacology · 2021Review
- Putative functional pathogenic autoantibodies in systemic sclerosis.European journal of rheumatology · 2020Review
- The Pathogenesis of Systemic Sclerosis: An Understanding Based on a Common Pathologic Cascade across Multiple Organs and Additional Organ-Specific Pathologies.Journal of clinical medicine · 2020Review
- Pathogenic roles of autoantibodies in systemic sclerosis: Current understandings in pathogenesis.Journal of scleroderma and related disorders · 2020Review
- Detecting gastrointestinal manifestations in patients with systemic sclerosis using anti-gAChR antibodies.Arthritis research & therapy · 2020Article
- Ganglionic Acetylcholine Receptor Antibodies and Autonomic Dysfunction in Autoimmune Rheumatic Diseases.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Systemic sclerosis (SSc) IgGs affecting the M(3)-muscarinic receptor (M(3)-R) have been proposed to be responsible for the gastrointestinal (GI) dysmotility in this disease. However, the effect of SSc IgGs on smooth muscle cell (SMC) function has not been studied. We determined the effect of SSc IgGs on the muscarinic receptor activation by bethanechol (BeCh; methyl derivate of carbachol) in SMC and smooth muscle strips from rat internal anal sphincter. IgGs were purified from GI-symptomatic SSc patients and normal volunteers, with protein G-Sepharose columns. SMC lengths were determined via computerized digital micrometry. The presence of M(3)-R and IgG-M(3)-R complex was determined by Western blot. IgGs from SSc patients but not from normal volunteers caused significant and concentration-dependent inhibition of BeCh response (P < 0.05). The maximal shortening of 22.2 +/- 1.2% caused by 10(-4) M BeCh was significantly attenuated to 8.3 +/- 1.2% by 1 mg/ml of SSc IgGs (P < 0.05). Experiments performed in smooth muscle strips revealed a similar effect of SSc IgG that was fully reversible. In contrast to the effect on BeCh, the SSc IgGs caused no significant effect (P > 0.05) on K(+) depolarization and alpha(1)-adrenoceptor activation by phenylephrine. Western blot studies revealed the specific presence of SSc IgG-M(3)-R complex. SSc IgGs attenuated M(3)-R activation, which was reversible with antibody removal. These data suggest that SSc GI dysmotility may be caused by autoantibodies that inhibit the muscarinic neurotransmission. Future treatment of SSc patients may be directed at the removal or neutralization of these antibodies.
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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.