Antibody-Mediated Gastrointestinal Dysmotility in Scleroderma

摘要: Abstract Background & Aims : Defects in enteric excitatory neurotransmission have been proposed to underlie the gastrointestinal dysmotility associated with scleroderma (systemic sclerosis). This study investigated whether patients produce antibodies that inhibit M3-muscarinic or neurokinin receptor–mediated intestinal contractions, either directly via an effect on L-type voltage-gated calcium channels (VGCCs). Methods: Responses of mouse colon longitudinal muscle stimulation by muscarinic agonist carbachol (1–300 μmol/L) and neurokinin-1 -2 receptor agonists were measured absence presence serum (2%) immunoglobulin G (IgG) (0.3–1.0 mg/mL) from scleroderma, those other autoimmune disorders, healthy controls. The role VGCCs carbachol- tachykinin-evoked contractions was assessed using nicardipine. Results: inhibited Ig fractions 7 9 (limited diffuse forms), 4 primary Sjogren's syndrome, 3 secondary syndrome. controls did not contractions. Inhibition concentration-dependent; a maximum inhibition approximately 40% occurred at 0.6 mg/mL IgG. Both VGCC dependent. Patient sera had no responses stimulation, demonstrating lack inhibiting VGCCs. Conclusions: Functional specifically cholinergic may provide pathogenic mechanism for dysfunction seen scleroderma. GASTROENTEROLOGY 2002;123:1144-1150