Antibodies Spell Trouble in Crohn's Disease

A new study shows that when anti-microbial antibodies are present and have accumulated for years before a person is diagnosed with Crohn’s disease (CD), the disease is likely to be complicated at or shortly after diagnosis.

The study was conducted by Rok Seon Choung, MD, of the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, MN, and colleagues and was published on the website of Alimentary Pharmacology and Therapeutics on April 27, 2016.

The authors begin by pointing out, “Notably, at diagnosis, up to one-third of patients already present with a complicated phenotype (strictures or fistulae) which predicts worse outcomes over time.”

They go on to suggest “patients with a complicated phenotype at diagnosis may have already developed an aberrant immune response during a pre-clinical phase compared to patients with noncomplicated disease at diagnosis.”

In exploring this idea, they found that two studies showed anti-microbial antibodies are present years before diagnosis, which led them to hypothesize the antibodies could be associated with a more aggressive disease course. They describe the aim of the present study as being “to determine the prevalence and pattern of anti-microbial antibodies preceding the diagnosis of CD and to study their association with a complicated disease phenotype.”

The researchers used information from the PREDICTS (Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects) study to complete their work. They obtained sera from 100 military personnel with CD. The median age of diagnosis was 30, and 24 of them had developed at least one complication around the time of diagnosis; 5 of those had small bowel or colonic resection. “The earliest available serum sample for each patient was obtained at a median of 6.0 years before diagnosis, with a maximum interval of 19.5 years to diagnosis,” said the researchers.

In order to investigate the possible link between antibodies and CD complications, the researchers say, “we compared the number and titres of antibodies between 24 patients with complicated CD and 76 patients with non-complicated CD.” They go on to say, “For the first time we were able to describe the longitudinal changes seen in the preclinical stage of CD.” Also they were able to see an increase “in the proportion of positive markers approaching the time of CD diagnosis,” according to the study.

Additionally, they say, “we also described for the first time a significant association between the presence of serologic CD-associated antibodies prior to clinical diagnosis and complicated CD phenotypes at the time or close to diagnosis, with an inverse relationship between the time to first complication and the magnitude of serologic responses.” This study may be the first step in identifying a high-risk population which could be monitored and offered early preventive strategies or treatments.