To determine whether it is feasible to prevent or slow joint disease by stimulating lubricin production within the joint, “we have also just recently developed a mouse in which we can turn lubricin expression on and off using doxycycline,” said Dr. Warman. The investigators are also conducting in vitro studies of different forms of lubricin to assess the effect of each different form on cell growth, tissue localization, and surface lubrication, with the ultimate goal being to replace protein function in humans, he said.
Dr. Warman's team is hoping to apply the research findings to more common joint diseases as well. To determine whether lubricin replacement therapy could also be useful for patients with osteoarthritis and rheumatoid arthritis, Dr. Warman and his colleagues are investigating lubricin changes in the cartilage and synovial fluid of patients with those conditions. “If we identify acquired changes in CACP protein among these patients, then therapies aimed at increasing endogenous protein synthesis or diminishing protein degradation may become valuable therapeutic adjuncts,” he said.
Although molecular testing to diagnose CACP or to identify unaffected characters is not yet available, the identification of the basic molecular components involved in the development of CACP is heading in this direction. Such tests will be especially useful for differentiating CACP from other conditions with which it shares many clinical features, such as polyarthritic and systemic juvenile idiopathic arthritis, in which pericarditis occasionally occurs. The ability to identify the genetic cause of a constellation of symptoms can help direct appropriate treatment and avoid the use of ineffective agents and their potential side effects.
In the absence of definitive molecular testing, CACP is best differentiated from other conditions by the presence of certain clinical, laboratory, and radiologic features. Particularly important, according to Dr. Offiah, is the lack of clinical signs of inflammation. “[CACP syndrome] is not associated with inflammatory changes in the synovium. Also, erythrocyte sedimentation rate, C-reactive protein, and complete blood count are normal,” she said. In addition, autoantibodies, including antinuclear antibodies and rheumatoid factor, are negative.
Among the distinguishing radiologic features of CACP are nonerosive arthropathies with smooth flattening of the affected joint surfaces, squaring of the metacarpal and phalangeal heads, coxa vara, short femoral neck, osteopenia, and large acetabular cysts that can be seen on pelvic X-ray.
To date, no effective treatment has been developed for CACP. However, recognition of the condition is important in order to prevent the use of inappropriate and potentially dangerous medications, said Dr. Warman, as well as offer insight into optimal treatment strategies for more common joint conditions.