Change in Sialic Acid in Pulmonary Arterial Hypertension

Abstract

Sialic acid (SA) is a vital component of the cellular glycocalyx. Increased serum levels of SA are found in cancers and cardiovascular disease. The levels of free and total SA in pulmonary arterial hypertension (PAH) are unknown. PAH is often undiagnosed until the patient is near or in heart failure, and right heart catheterization is required for diagnosis. Knowing that serum SA is increased in other diseases, we asked whether it was also increased in PAH. Levels of free and total SA were measured in the serum of three groups: healthy volunteers (HV), idiopathic PAH (IPAH), and connective tissue disease‐associated PAH (CTD). While total SA does not change significantly between groups, free SA in IPAH and CTD serum is increased compared to HV serum. In addition, PAH patients have anti‐endothelial cell antibodies. Antibodies are highly glycosylated proteins whose function may be altered by changes in sialylation. We asked whether IgG from PAH patients contains increased SA as compared to IgG from healthy volunteers. IgG was purified from serum by affinity chromatography. Samples were hydrolyzed and total SA was measured. IPAH IgG shows an increased percentage of SA as compared to HV or CTD IgG. Collectively, these results suggest that PAH changes the sialylation patterns of immunoglobulins and possibly their antigenic targets. SA levels may also be a useful biomarker for diagnosing PAH. Supported by R00HL089361.