Serum depletion of complement component 5a is associated with increased inflammation and poor clinical outcomes in patients with perianal fistulas


Advocate Illinois Masonic Hospital


Background: Persistent disease is a significant issue in the management of perianal fistulas, with up to 50% of patients representing following surgery and requiring additional treatment.

Objective: The purpose of this study was to identify a novel prognostic modality in hopes of risk stratifying patients for persistent disease following corrective surgery.

Design: This was a retrospective study based on prospectively collected data using a combination of histopathology, high throughput proteomic arrays, and ELISA based methods.

Settings: This study used data on patients who underwent corrective surgery for perianal fistulas at the University of Illinois Hospital between June 2019 and July 2020.

Patients: A cohort of 22 consecutive patients who corrective surgery for perianal fistulas was included in this study. The patients were divided into 2 groups: those with resolving fistulas (N = 13) and those with persisting fistulas (N = 9).

Main outcome measures: Non-resolving fistulas were determined by disease re-presentation within 2 months of corrective surgery.

Results: Serum samples from patients with persistent perianal fistulas displayed a consistent decrease in the expression of complement pathway component C5a compared to either healthy controls or patients with resolving forms of disease. This was paralleled by an increase in fistula expression of C5a and an associated increase in tissue infiltrating leukocytes and IL-1β expression.

Limitations: The study was limited by its retrospective design, relatively small sample size, and single center data analysis.

Conclusions: These results suggest that C5a is modestly depleted in patients with non-resolving forms of disease, and traffics to the site of tissue damage and inflammation. Accordingly, serum C5a warrants continued investigation as a prognostic biomarker and predictor of recurrence in patients presenting with perianal fistulas. See Video Abstract at http://links.lww.com/DCR/B982.

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