Autoantibodies cause calcium (blue) to accumulate in rat heart cells.

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.