One in five asymptomatic relatives of Crohn's patients had persistently raised calprotectin

Design

Screening cohort for a prevention trial

Population

331 asymptomatic first-degree relatives of people with Crohn's, aged 6-38

Primary outcome

Persistent calprotectin elevation and endoscopic findings

Effect

19% persistently raised; 2.7% presymptomatic Crohn's; >225 µg/g AUC 0.97

A screening study in Gut, published on 7 October 2026, reports the pre-trial stage of PIONIR, a diet-based prevention trial. Asymptomatic first-degree relatives of people with Crohn's disease, aged 6 to 38, had faecal calprotectin measured; those above 70 µg/g on at least two tests were offered capsule endoscopy or ileocolonoscopy.

Of 331 relatives screened, 63 (19%) had persistently raised calprotectin. Of 42 who were examined, 9 (2.7% of those screened) had appearances compatible with presymptomatic Crohn's disease, 22 had non-specific mucosal changes and 11 had normal mucosa. A calprotectin above 225 µg/g identified presymptomatic Crohn's with an area under the curve of 0.97 (sensitivity 89%, specificity 94%). About a fifth of single raised values normalised on repeat.

The study defines a group for prevention trials. It is not a case for screening relatives in routine practice, since no intervention has yet been shown to prevent Crohn's, and the numbers with confirmed preclinical disease were small.

• Do not screen asymptomatic relatives of Crohn's patients with calprotectin outside research.
• Repeat a single raised calprotectin before acting; about one in five normalised.
• Investigate promptly when a relative of someone with Crohn's develops symptoms, given their raised risk.
• Treat very high calprotectin (above about 225 µg/g) in an at-risk relative as a strong prompt for endoscopic assessment if symptoms are present.

Why it matters

It marks a measurable preclinical phase of Crohn's that prevention trials can now target.

Don't overread it

Only nine people had presymptomatic Crohn's; the accuracy figures rest on small numbers.

The statistics, in plain English

An area under the curve of 0.97 means the threshold separated those with and without presymptomatic Crohn's very well in this group, but with only nine cases the estimate could shift in a larger sample.

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