Sjögren autoantibodies modify neonatal cardiac function via M₁ muscarinic acetylcholine receptor activation

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• 作者：Borda ; Enri ; Perez Leiros ; Claudia ; Bacman ; Sandra ; Berra ; Alejandro ; Sterin-Borda ; Leonor
• 关键词：Primary Sjö ; gren syndrome ; Congenital heart block ; M₁ muscarinic acetylcholine receptor autoantibodies ; Neonatal heart contractility ; Indirect immunofluorescence ; Phosphoinositide turnover ; Nitric oxide synthase activity ; Human M₁
• 刊名：International Journal of Cardiology
• 出版年：1999
• 期刊代码：128_01675273
• 类别：med
• 出版时间：July 1, 1999
• 卷：70
• 期：1
• 页码：23-32
• 文件大小：554 K

摘要

Isolated congenital heart block may be associated with primary Sjögren syndrome. In this work we describe circulating antibodies in the sera of primary Sjögren syndrome patients that are able to interact with neonatal myocardium by activating muscarinic acetylcholine receptors of M₁ subtype. We report on the presence of autoantibodies against the second extracellular loop of human M₁ muscarinic acetylcholine receptors in primary Sjögren syndrome mothers whose children have congenital heart block using a synthetic peptide in indirect immunofluorescence technique. Autoantibodies from primary Sjögren syndrome patients gave positive image on neonatal atria but not on adult atria slices. The synthetic M₁ peptide selectively abrogated indirect immunofluorescence recognition. The primary Sjögren syndrome–immunoglobulin G also displayed an ‘agonist like’ activity modifying the intracellular events associated with muscarinic acetylcholine receptor activation. The mechanism appears to occur secondarily to stimulation of phosphoinositides turnover via phospholipase C activation. This, in turn, triggers cascade reactions involving calcium/calmodulin and leads to activation of nitric oxide synthase and soluble guanylate cyclase. All of these effects were selectively blunted by pirenzepine and neutralized by M₁ synthetic peptide. These biological effects were not obtained using adult instead of neonatal rat atria and neither occurred with the sera of normal healthy women of childbearing age. It could be concluded that antibodies against neonatal M₁ muscarinic acetylcholine receptor may be another serum factor to be considered in the pathophysiology of the development of congenital heart block associated with primary Sjögren syndrome mothers.