Serum Sulfatide Levels as a Biomarker of Active Glomerular Lesion in Patients with Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single Center Pilot Study

Abstract

Sulfatides are glycosphingolipids that are associated with coagulation and platelet aggregation. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) activates platelet function and often leads to thrombotic complications. These facts suggest an association between serum sulfatides and AAV. We aimed to clarify the significance of serum sulfatide levels in patients with AAV. We conducted a retrospective, single-center, observational pilot study that included 35 patients who developed AAV and 10 control patients who were candidates for living-donor kidney transplantation. We compared serum sulfatide levels between the control and AAV patients. We analyzed the differences in serum sulfatide levels among four classes (focal, crescentic, mixed, and sclerotic class) of glomerular lesions that were categorized by histopathologic classification of ANCA-associated glomerulonephritis. Serum sulfatide levels in patients with AAV were significantly lower than those in the controls. Serum sulfatide levels were significantly different between the four classes. Additionally, serum sulfatide levels in the crescentic class were significantly lower than those in the other classes. Serum sulfatide levels were significantly correlated with albumin, cholesterol, C-reactive protein, and pentraxin 3. In conclusion, serum sulfatide levels are significantly correlated with inflammation, reflecting crescentic glomerulonephritis, which is an active glomerular lesion in AAV patients.

Serum sulfatide level is associated with severe systemic vasculitis with kidney involvement

“…Consistent with the results of our pilot study ( 2 ), the SS level was significantly lower in crescentic class patients in the AAV group. The detection ability of the SS level for such patients was sufficiently high, and the combined formulae of the SS level and other predictors showed higher detection results.…”

“…We randomly selected 50 IgAN patients from among 189 candidates for the analysis. Ten donors and 35 patients with AAV who were admitted between 1 January 2013 and 31 December 2019 and evaluated in our previous study ( 2 ) were also included in the present investigation.…”

“…As a type of glycosphingolipid, 3-O-sulfogalactosylceramides (sulfatides) are abundantly found in the brain, kidney, and digestive tract as well as on platelet surfaces ( 1 , 2 ). These lipids are also synthesized in the liver and secreted into the serum with lipoproteins ( 3 , 4 ).…”

“…Given that vasculitis activates platelets and inflammation-related molecules ( 13 ), SSs are thought to be related to SV diseases with kidney involvement (SVKI). Our earlier pilot study revealed that the SS level in patients with AAV was significantly lower than that in healthy controls, and that a lower SS level was associated with active pathological findings on kidney biopsy ( 2 ). Those results suggested a significant contribution of SSs in the regulation of SVKI as well as a potential clinical utility of the SS level measurement.…”

Investigation of Clinical Features and Association between Vascular Endothelial Injury Markers and Cytomegalovirus Infection Associated with Thrombotic Microangiopathy in Patients with Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: Case-Based Research

“…Soluble thrombomodulin and pentraxin 3 are well-known vascular endothelial injury markers. Additionally, we recently reported novel vascular injury markers, serum sulfatides, which are associated with the pathological activity of kidney lesions in patients with AAV [13]. Sulfatides are one of the glycosphingolipids measured using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and their low levels may indicate not only severe vascular endothelial injury but also platelet activation.…”