Lack of autoantibodies against collagen and related proteins in collagenous colitis

Abstract

Introduction: Collagenous colitis (CC) is a common cause of chronic diarrhea and is characterized by a subepithelial thickened collagen layer in the colonic mucosa. It shares many of the characteristics found in autoimmune diseases, but no autoantibodies have been identified. In CC, an imbalance in collagen turnover is evident. The purpose of the present study was to investigate whether any collagen-associated autoantibodies or other antibodies such as TPO and ASCA were present, and if levels of total IgE were increased.

Methods: Sera from women with active CC were analysed with ELISA for detection of autoantibodies against collagen type III and IV (Col III and IV), matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and tenascin-C (TNC). Sera were also analysed for TPO, ASCA and total IgE. Healthy female blood donors served as controls. The cut-off value in the control group was defined as relative units > 97.5th percentile.

Results: Sixty-six women were included (mean age 60 years; range 31-74, mean disease duration 6 years; range 1-22). No autoantibody was significantly overexpressed in the CC population compared to controls. The mean disease duration was lower (p = 0.03) in the subjects who expressed collagen-associated autoantibodies (3.7 years; range 1-14), compared to those who did not (6.4 years; range 1-22). Treatment with budesonide was not associated with any of these autoantibodies.

Conclusion: No increased presence of the investigated antibodies could be found in the present study of CC. Neither could antibodies against ASCA or TPO, or elevated levels of IgE, be found. Consequently, no association was found between CC and these proteins, even though this may not be generalizable to other compounds in the collagen layer.

Keywords: Autoantibodies; Autoimmunity; Collagen type III; Collagen type IV; Collagenous colitis; MMP-9; TIMP-1; Tenascin.

Fig. 1

Histological features of collagenous colitis. High magnification micrograph of collagenous colitis, H&E stain (Collagenous colitis—high mag—Collagenous colitis—Wikipedia) by Michael Bonert, MD, FRCPC. Copyright © 2011 Michael Bonert, MD, FRCPC (https://commons.wikimedia.org/wiki/User:Nephron / https://fhs.mcmaster.ca/pathology/contact_us/faculty/faculty_bios/Bonert.html. Licensed under CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0/legalcode)

Fig. 2

Levels of collagen-associated antibodies in patients with collagenous colitis and controls. Col III = collagen type III, Col IV = collagen type IV, MMP-9 = matrix metalloproteinase-9, TIMP-1 = tissue inhibitors of metalloproteinases-1, TNC = tenascin-C. CC = collagenous colitis (n = 66); treated = current budesonide treatment, controls = healthy blood donors (n = a 70, b 51, c 100, d 65, e 100). Black bars state median values. Y axis: Antibody levels in relative units (RU) (absorbance values after subtracted background). Cut-off value set at the 97.5 th percentile. Fischer's exact test was used to calculate the differences between controls and CC pat (including both treated and untreated)

Fig. 3

a Presence of collagen-associated autoantibodies. Col III = collagen type III, Col IV = collagen type IV, MMP-9 = matrix metalloproteinase-9, TIMP-1 = tissue inhibitors of metalloproteinases-1, TNC = tenascin-C, CC = collagenous colitis. Relative units > 97.5 percentile in a cohort of healthy blood donors were considered as presence of antibodies. Controls consisted of α = 70, β = 51, γ = 100, δ = 65 healthy blood donors. Fischer's exact test was used to calculate the differences between groups. None of the differences between groups were statistically significant (P < 0.05). b Presence of antibodies against saccharomyces cerevisiae (ASCA), thyroid peroxidase (TPO) and increased total serum IgE. CC = Collagenous colitis. Controls consisted of α = 50 healthy blood donors, β = 254 healthy blood donors, γ = 100 healthy blood donors. Fischer's exact test was used to calculate the differences between groups. None of the differences between groups were statistically significant (P < 0.05)