Authors’ Response to Letter to Editor: “Evaluating Serum Free Thiols in Inflammatory Bowel Disease: Contribution of Albumin to Extracellular Free Thiol Status”

Abstract

We thank Bourgonje et al for their insightful letter and comments regarding our article “Prospective Evaluation of Serum Free Thiols in Inflammatory Bowel Disease: A Candidate to Replace C-Reactive Protein for Disease Activity Assessment?” (Bohra et al), published in Inflammatory Bowel Diseases.1,2 Our work in prospective evaluation of serum free thiols (FTs) was certainly inspired and informed by their previous study, and we acknowledge the principles underlying their methodology of adjusting the serum thiol groups by albumin.2,3Although the rationale for adjusting serum FTs for albumin from a theoretical, laboratory perspective may be sound, we also believe that adjusting for albumin in the context of inflammatory disorders such as IBD may not be clinically appropriate for the following reasons. First, in our own preliminary analyses of our cohort we did analyze our serum FT data adjusting for albumin, but this did not enhance the performance of serum FTs for prediction of endoscopically active disease. Secondly, serum albumin is not only implicated in binding extracellular FTs but is itself prone to significant variation across an IBD cohort given its role as an acute phase reactant, the effect of intestinal protein losses and the disparate impact of disease location and severity on protein malabsorption and/or insufficient protein intake, amongst other patient factors.4 Thirdly, as Bourgonje et al have summarized eloquently, the interplay of serum FTs and their redox status with protein binding (including albumin and other serum proteins) and the inflammatory milieu is inherently complex.2,5,6 Hence, this area of research requires further elucidation before we can confidently apply such knowledge to clinical settings, including biomarkers like serum thiols in inflammatory bowel disease.