Esophagus to Small Intestine
Gut. 2023;72(3):443–50
Distinct blood protein profiles associated with the risk of short-term and mid/long-term clinical relapse in patients with Crohn’s disease stopping infliximab: When the remission state hides different types of residual disease activity
Objective: Despite being in sustained and stable remission, patients with Crohn’s disease (CD) stopping anti-tumor necrosis factor α (TNFα) show a high rate of relapse (~50% within 2 years). Characterizing non-invasively the biological profiles of those patients is needed to better guide the decision of anti-TNFα withdrawal.
Design: 92 immune-related proteins were measured by proximity extension assay in serum of patients with CD (n = 102) in sustained steroid-free remission and stopping anti-TNFα (infliximab). As previously shown, a stratification based on time to clinical relapse was used to characterize the distinct biological profiles of relapsers (short-term relapsers: < 6 months vs. mid/long-term relapsers: > 6 months). Associations between protein levels and time to clinical relapse were determined by univariable Cox model.
Results: The risk of mid/long-term clinical relapse (HR = hazard in patients above the cut-off/hazard in patients under the cut-off) was specifically associated with a high serum level of proteins mainly expressed in lymphocytes (LAG3, SH2B3, SIT1; HR = 2.2–4.5; p < 0.05), a low serum level of anti-inflammatory effectors (IL-10, HSD11B1; HR = 0.2–0.3; p < 0.05) and cellular junction proteins (CDSN, CNTNAP2, CXADR, ITGA11; HR = 0.4; p < 0.05). The risk of short-term clinical relapse was specifically associated with a high serum level of pro-inflammatory effectors (IL-6, IL12RB1; HR = 3.5–3.6; p < 0.05) and a low or high serum level of proteins mainly expressed in antigen-presenting cells (CLEC4A, CLEC4C, CLEC7A, LAMP3; HR = 0.4–4.1; p < 0.05).
Conclusion: The authors identified distinct blood protein profiles associated with the risk of short-term and mid/long-term clinical relapse in patients with Crohn’s disease stopping infliximab. These findings constitute an advance for the development of non-invasive biomarkers guiding the decision of anti-tumor necrosis factor α withdrawal.