Long Term Stability of Serology Markers in Crohn's Disease (CD) Patients: A Longitudinal Analysis From Repeated Measurements

Abstract

Serology markers currently have a diagnostic role in CD. A better understanding of their long term stability and their relationship to the clinical course of disease is of potential interest. Methods: Banked blood samples were obtained from 126 CD patients who were participants in the population-based Manitoba IBD Cohort Study, a study of subjects enrolled within 7 years of diagnosis and followed longitudinally. Diagnosis of CD was confirmed by chart review. The initial blood sample was obtained at a mean of 4.3 years of disease; the second blood sample was obtained 5 years after the first. Both samples were assayed by ELISA at Prometheus Laboratories for the following serologic markers: ANCA, ASCA IgA and IgG, anti-CBir1, anti-OmpC, anti-I2. The assays were undertaken blinded and mixed with an additional 244 cases of UC and indeterminate colitis. To assess stability at a population level, the medians for each serology marker were calculated for both the initial and second samples. At an individual patient level, the change in each marker was calculated for each patient and the medians of these changes were determined. In order to assess the stability of the combined immune response, the raw marker data for each patient from both time points was converted to a quartile score using the test results from the first blood draw to define the quartiles. The quartile scores were combined into a quartile sum score (QSS, range 6 -24) and the change in the QSS between the initial and later blood samples was determined. Results: The serologic response appears to be substantially stable over time at both a population and at the individual patient level. Table 1 shows the population median expression levels (values are ELISA units, EU) for each marker at the early and later time points. The medians either fell or rose weakly over time. For the individual patients, the median changes in marker expression were ANCA (1 EU), ASCA-A (-0.8 EU), ASCA-G (0.6 EU), antiCBir1 (-2.6 EU), anti OmpC (0.1 EU) and anti I2 (6 EU) indicating minimal change from the initial to the later sample. In addition, 85% of patients had an absolute change in QSS of <4 (or 93% if the UC marker ANCA was not included) demonstrating stability of the combined immune response. Conclusions:The serologic response in CD reflects a compromised immune reaction in these patients. In this study the level of expression of the individual serology markers ANCA, ASCA IgA and IgG, anti-CBir1, anti-OmpC, antiI2 and of the markers combined as QSS has been shown to be stable for CD patients when comparing blood samples taken 5 years apart. Further work will explore whether there are clinical differences between those subjects with unstable antibody levels compared to the majority with stable levels. Median serological marker expression (EU)