Heart-stopping antibodies
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《实验药学杂志》
Women with lupus and rheumatoid arthritis are at increased risk for having babies with congenital heart block, and maternal autoantibodies that cross the placenta are thought to be the main cause. On page 11, Salomonsson et al. show that a subset of autoantibodies that disrupt the calcium homeostasis in heart cells is responsible.Women with autoantibodies specific for an intracellular protein of unknown function called SSA/Ro52 (Ro52) are more likely to have babies with congenital heart block—a condition in which the electrical impulses that regulate the heart beat are disrupted. The pathogenic response has been associated with the presence of antibodies that bind to one peptide on Ro52 called p200, but the mechanism was until recently a mystery.
The authors have now pinpointed the pathogenic response even further by showing that not all p200-specific antibodies cause disease. They cloned two antibodies from rheumatic patients, which both recognized p200 but had distinct binding properties. One of these antibodies, but not the other, bound to neonatal rat heart cells and deregulated calcium homeostasis. Intracellular calcium accumulated in these cells, eventually triggering apoptosis. When sera from newborn children with congenital heart block were analyzed, there was a predominance of antibodies with binding properties similar to those of the pathogenic subset of p200-specific maternal antibodies.
The mechanism by which these antibodies interfere with normal calcium flux remains unsolved. The authors believe that in vivo the p200-specific antibodies bind not to intracellular Ro52 but to a cross-reacting protein on the cell surface. They are now trying to identify that protein but meanwhile hope that this study will provide a new way to identify women who are most at risk for having children with congenital heart block.
Heather L. Van Epps
hvanepps@rockefeller.edu
Related Article
Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block
Stina Salomonsson, Sven-Erik Sonesson, Lars Ottosson, Saad Muhallab, Tomas Olsson, Maria Sunnerhagen, Vijay K. Kuchroo, Peter Thorén, Eric Herlenius, and Marie Wahren-Herlenius
J. Exp. Med. 2005 201: 11-17.(Heather L. Van Epps)
The authors have now pinpointed the pathogenic response even further by showing that not all p200-specific antibodies cause disease. They cloned two antibodies from rheumatic patients, which both recognized p200 but had distinct binding properties. One of these antibodies, but not the other, bound to neonatal rat heart cells and deregulated calcium homeostasis. Intracellular calcium accumulated in these cells, eventually triggering apoptosis. When sera from newborn children with congenital heart block were analyzed, there was a predominance of antibodies with binding properties similar to those of the pathogenic subset of p200-specific maternal antibodies.
The mechanism by which these antibodies interfere with normal calcium flux remains unsolved. The authors believe that in vivo the p200-specific antibodies bind not to intracellular Ro52 but to a cross-reacting protein on the cell surface. They are now trying to identify that protein but meanwhile hope that this study will provide a new way to identify women who are most at risk for having children with congenital heart block.
Heather L. Van Epps
hvanepps@rockefeller.edu
Related Article
Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block
Stina Salomonsson, Sven-Erik Sonesson, Lars Ottosson, Saad Muhallab, Tomas Olsson, Maria Sunnerhagen, Vijay K. Kuchroo, Peter Thorén, Eric Herlenius, and Marie Wahren-Herlenius
J. Exp. Med. 2005 201: 11-17.(Heather L. Van Epps)