Antibody-mediated gastrointestinal dysmotility in scleroderma

Area of Science:

• Gastroenterology
• Immunology
• Neuroscience

Background:

• Gastrointestinal dysmotility is common in scleroderma (systemic sclerosis).
• Defects in enteric excitatory neurotransmission are a proposed cause.
• This study investigates antibodies affecting intestinal contractions in scleroderma patients.

Purpose of the Study:

• To determine if scleroderma patients produce antibodies inhibiting M3-muscarinic or neurokinin receptor-mediated intestinal contractions.
• To assess if these antibodies affect L-type voltage-gated calcium channels (VGCCs).

Main Methods:

• Mouse colon muscle contractions were measured.
• Responses were tested with carbachol (M3 agonist) and neurokinin receptor agonists.
• The effects of serum/IgG from scleroderma patients, other autoimmune patients, and controls were analyzed.
• Nicardipine was used to assess L-type VGCC involvement.

Main Results:

• IgG from 7/9 scleroderma patients inhibited M3-muscarinic receptor contractions.
• IgG from Sjögren's syndrome patients also showed inhibition.
• No inhibition of neurokinin receptor responses or VGCCs was observed.
• Inhibition was concentration-dependent, reaching ~40% at 0.6 mg/mL IgG.

Conclusions:

• Functional antibodies specifically inhibiting M3-muscarinic receptor neurotransmission may be pathogenic in scleroderma.
• This offers a potential mechanism for gastrointestinal dysfunction in scleroderma patients.