Abnormalities in Complement and Scleroderma-PAH

We previously showed that scleroderma patients with pulmonary arterial hypertension (PAH) have elevated blood levels of complement factor D (adipsin). When we then found that our TNF-Tg mice with pulmonary hypertension also have evidence of an abnormal complement cascade, this launched an investigation to determine the role of complement in SSc-PAH. To this end, we are using our TNF mice to identify whether genetic or pharmacologic inhibition of complement may be able to prevent/treat PAH.  In addition, we are doing further biomarker assessment of the entire complement cascade in large numbers of patients with SSc-PAH and looking to correlate the complement levels with important clinical findings.  Lastly, we are looking for genetic abnormalities in the complement system to determine if this may predispose patients to develop PAH.