Serum Sphingomyelin/Ceramide Ratios Identify Concomitant Primary Sclerosing Cholangitis in Inflammatory Bowel Disease

Background/Objectives: Non-invasive markers of primary sclerosing cholangitis (PSC) in patients with inflammatory bowel disease (IBD) are lacking, and serum ceramide species are altered in both diseases. This study investigated whether total and species-specific serum sphingomyelin-to-ceramide (SM/Cer) ratios identify concomitant PSC in IBD and reflect inflammatory activity. Methods: Serum SM and ceramide species were quantified by direct flow injection analysis–mass spectrometry in 16 healthy controls, 57 patients with IBD, 7 patients with PSC, and 13 patients with PSC-IBD. The total SM/Cer ratio and six species-specific ratios were analyzed in relation to IBD, PSC-IBD, inflammation markers, stool consistency, and medication. Results: The total SM/Cer and SM 42:1;O2/Cer 18:1;O2/24:0 ratios discriminated PSC-IBD from those with IBD alone, with areas under the receiver operating characteristic curve of 0.76 and 0.82, specificities of 95% and 91%, and sensitivities of 62% and 69%, respectively. Their diagnostic performance was comparable to that of the corresponding ceramide species. Combining the SM/Cer ratios with alkaline phosphatase and bilirubin levels improved diagnostic performance compared with standard laboratory measures alone. Moreover, multiple linear regression revealed that the SM/Cer ratios were less confounded by age and fecal calprotectin than the individual ceramide species levels. The SM 36:1;O2/Cer 18:1;O2/18:0 and SM 38:1;O2/Cer 18:1;O2/20:0 ratios were lower in patients with IBD, PSC, and PSC-IBD than in controls. Of these, only the latter ratio correlated negatively with inflammatory markers. Associations of SM/Cer ratios with current medication and stool consistency were modest and require further validation. Conclusions: Serum total SM/Cer and SM 42:1;O2/Cer 18:1;O2/24:0 ratios identify concomitant PSC in patients with IBD with high specificity, while fecal calprotectin has little or no effect on these ratios. Because they need only a small serum sample, these ratios are promising non-invasive markers for selecting patients with IBD for cholangiographic evaluation. Validation in larger, prospective cohorts is needed.