C0374 - Fecal Calprotectin Level Is Nonlinearly Associated With GI Pathogen Detection by PCR in Patients With and Without Inflammatory Bowel Disease

Monday, October 24, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

Kira L. Newman, MD, PhD

University of Michigan
Ann Arbor, MI

Kira L. Newman, MD, PhD, Peter D. Higgins, MD, PhD, MSc
University of Michigan, Ann Arbor, MI

Introduction: Fecal calprotectin (FCP) is an inflammatory marker frequently used to monitor inflammatory bowel disease (IBD) activity, but it can also be elevated in gastrointestinal infections. The impact of infections on FCP level in people with IBD has not been well described across pathogens. The objective of our study was to quantify the relationship between FCP levels and lab-confirmed infections in people with and without IBD.

Methods: We performed a retrospective cohort study at a tertiary-care referral center of inpatient and outpatient encounters during which FCR and gastrointestinal pathogen polymerase-chain reaction (GI PCR) testing were conducted. Using non-parametric tests and quantile regression, we compared FCP levels between individuals with and without IBD and with and without pathogen detection.

Results: There were 3,399 encounters with FCP and GI PCR testing from 2,780 unique individuals between August 1, 2016 and February 17, 2022. Overall, 1819 (53.5%) encounters were individuals with IBD (n=1,819, Table). Pathogens were detected in 757 encounters (22.3%). There was no significant difference in pathogen detection or pathogen type between groups with and without IBD (p >0.9). The median FCP was 46 mg/kg in individuals without IBD and 265 mg/kg in those with IBD (p< 0.001). Among individuals without IBD, the median FCP was significantly elevated when a pathogen was detected (64 vs. 41 mg/kg, p=0.0003, Figure), but FCP was not significantly elevated among those with IBD when a pathogen was detected (299 vs. 255 mg/kg, p=0.207). After adjusting for age and IBD status in quantile regression, pathogen detection was only significantly associated with higher FCP in the lower two quartiles, though IBD remained significantly associated with higher FCP at all levels (p >0.001). After adjusting for IBD and age, FCP was significantly associated with detection of bacterial pathogens and multiple pathogens in the lower two quartiles.

Discussion: Pathogen detection by GI PCR is associated with elevated FCP, though this relationship is nonlinear and varies by IBD status. Even after stratifying by IBD status, there is significant variability in FCP, suggesting that factors in addition to infection may be playing a role, including potentially measurement error, or a greater immune reaction to pathogen infection in IBD leading to mild flares. Our findings indicate that FCP may be an adjunct to, but not a substitute for stool pathogen testing.

Figure: Fecal calprotectin levels by stool pathogen testing result and inflammatory bowel disease (IBD) diagnosis.

Variable	Overall N = 3,347¹	IBD diagnosis		p-value²
		No IBD N = 1,528¹	IBD N = 1,819¹
Fecal calprotectin (mg/kg)	107 (31, 498)	46 (24, 168)	265 (56, 903)	< 0.001
Pathogen detected	744 (22%)	340 (22%)	404 (22%)	>0.99
Age (years)	39 (25, 57)	41 (23, 61)	38 (26, 55)	0.02
Sex				< 0.001
Female	2,013 (60%)	988 (65%)	1,025 (56%)
Male	1,333 (40%)	540 (35%)	793 (44%)
Race				0.13
African American	332 (9.9%)	135 (8.8%)	197 (11%)
American Indian or Alaska Native	5 (0.1%)	3 (0.2%)	2 (0.1%)
Asian	92 (2.8%)	51 (3.3%)	41 (2.3%)
Caucasian	2,768 (83%)	1,277 (84%)	1,491 (82%)
Native Hawaiian and Other Pacific Islander	1 (< 0.1%)	1 (< 0.1%)	0 (0%)
Other	113 (3.4%)	49 (3.2%)	64 (3.5%)
Patient Refused	18 (0.5%)	5 (0.3%)	13 (0.7%)
Unknown	16 (0.5%)	7 (0.5%)	9 (0.5%)
Ethnicity				0.35
Hispanic or Latino	89 (2.7%)	49 (3.2%)	40 (2.2%)
Non-Hispanic or Latino	3,193 (96%)	1,449 (95%)	1,744 (96%)
Patient Refused	22 (0.7%)	10 (0.7%)	12 (0.7%)
Unknown	39 (1.2%)	18 (1.2%)	21 (1.2%)
Inpatient encounter	1,435 (43%)	523 (34%)	912 (50%)	< 0.001

Table: Characteristics of patients with and without IBD who had fecal calprotectin and gastrointestinal pathogen testing. 1 Median (IQR); n (%) ; 2 Wilcoxon rank sum test; Pearson's Chi-squared test; Fisher's exact test

Disclosures:

Kira Newman indicated no relevant financial relationships.

Peter Higgins: AbbVie – Consultant. Amgen – Consultant. Eli Lilly – Consultant. Gastrointestinal Health Foundation – Consultant. Genentech – Consultant. Imedex – Consultant. JBR Pharma – Consultant. Lycera – Consultant. National Institutes of Health – Grant/Research Support. Pfizer – Consultant. Takeda – Consultant, Grant/Research Support. The Crohn’s & Colitis Foundation – Grant/Research Support. Vindico Medical Education – Consultant.

Kira L. Newman, MD, PhD, Peter D. Higgins, MD, PhD, MSc. C0374 - Fecal Calprotectin Level Is Nonlinearly Associated With GI Pathogen Detection by PCR in Patients With and Without Inflammatory Bowel Disease, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.