Serologic microbial associated markers can predict Crohn's disease behaviour years before disease diagnosis

Abstract

Summary Background Patients with Crohn's disease (CD) have serologic responses to various microbial antigens. Serologic markers are associated with aggressive forms of disease and can be detected before onset of symptoms. Their utility in pre‐clinical disease or prediction of complicated disease course before diagnosis is unclear. Aim To evaluate the pattern of serologic anti‐microbial antibodies long prior to diagnosis and the subsequent risk of complicated Crohn's disease at diagnosis. Methods Sera from 100 US military personnel with Crohn's disease were obtained from the Department of Defense Serum Repository. For each patient, four samples were obtained at different time points before and around diagnosis, and were tested for 6 microbiota‐directed antibodies (ASCA‐IgA, ASCA‐IgG, anti‐OmpC, anti‐CBir1, anti‐A4‐Fla2 and anti‐FlaX). Associations between the presence and accumulation of Crohn's disease anti‐microbial antibodies before diagnosis and with the later development of complications were evaluated. Results Overall, 65 patients were positive for at least one Crohn's disease associated anti‐microbial antibody in the earliest available sample, at a median of 6 years before Crohn's disease diagnosis (interquartile range, 5.6–8.2). The number of positive anti‐microbial antibodies increased up to the time of Crohn's disease diagnosis. Complicated disease developed around the time of diagnosis in 24 patients. The proportion of positive antimicrobial antibodies before diagnosis was higher in patients with complicated vs. noncomplicated Crohn's disease. There was an inverse relationship between the time to first complication and the magnitude of serologic response before diagnosis. Conclusion The presence and accumulation of circulating anti‐microbial antibodies years before Crohn's disease diagnosis was associated with complicated Crohn's disease at or shortly after diagnosis.

Uric acid levels are independent of anti-Saccharomyces cerevisiae antibodies (ASCA) in Crohn’s disease: A reappraisal of the role of S. cerevisiae in this setting

“…When investigating a large number of CD families we showed that CD and their first-degree healthy relatives (FDR) were more frequently colonized with C. albicans than control populations and in FDR the so far unexplained higher prevalence of ASCA with regard to control populations (30%) was associated with the carriage of C. albicans [31] In these studies, C. albicans represented 76–81% of the yeast species isolated compared to only 2–4% for S. cerevisiae . This increase in Candida abundance during CD in contrast with a reduction in S. cerevisiae revealed by culture methods was recently confirmed through NGS micro-mycobiome analysis by two independent groups [4,5]. Thus, the involvement of S. cerevisiae in CD is not supported by epidemiological, pathophysiological or immunological arguments, nor by the unconfirmed correlation between ASCA and UA.…”

“…The number of antigenic targets and the magnitude of the response, are indicative of disease severity [3], are now taken into account when defining the nature of initial treatment[4]. Similarly, their pre-existence to CD onset is increasingly considered in surveys of high risk populations[5]. Despite their widespread use, the mechanisms of generation and persistence of these antibodies remain unknown.…”

The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

“…Follow-up of people at risk in a longitudinal mode led to the identification of bacterial strains presence/absence and of microbiota diversity modifications as predictors of chronic disease onset or aggravation, as illustrated in Type 1 diabetes, systemic lupus erythematosus (SLE), Crohn's disease, cancers or food allergies [59][60][61][62][63][64]. Here also, monitoring may lead to preventive care measures, adaptation of clinical management and discovery of novel therapies by microbiota modifiers.…”

Editorial: serologic microbial‐associated markers to predict Crohn's disease behaviour

“…This study, and two other smaller studies, have shown the presence of serological markers before clinical diagnosis. [4][5][6] Choung et al present novel data to show that the gradual accumulation of serological markers over several years is associated with complications at, or soon after, clinical diagnosis. 6 This observation shows that Crohn's disease has an extended pre-clinical period, perhaps for 5-10 years.…”

“…[4][5][6] Choung et al present novel data to show that the gradual accumulation of serological markers over several years is associated with complications at, or soon after, clinical diagnosis. 6 This observation shows that Crohn's disease has an extended pre-clinical period, perhaps for 5-10 years. Over this time, there is gradual immune dysregulation and loss of tolerance of the gut immune system to normal microbiological flora.…”