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Increased Colonic Levels of CD8+ Cytotoxic T lymphocyte-Associated Mediators in Patients With Microscopic Colitis
Alexandra Lushnikova1, Anna Wickbom2, Johan Bohr2
1School of Medical Sciences, Örebro University, Örebro, Sweden.
Inflammatory Bowel Diseases
|April 10, 2025
Summary
Microscopic colitis patients show distinct immune mediator profiles compared to ulcerative colitis and controls. These differences suggest unique disease pathways for collagenous colitis and lymphocytic colitis.
Area of Science:
- Gastroenterology
- Immunology
- Oncology
Background:
- Microscopic colitis (MC), encompassing collagenous colitis (CC) and lymphocytic colitis (LC), is associated with a reduced risk of colorectal cancer compared to controls and ulcerative colitis (UC).
- The underlying immunological mechanisms for this reduced cancer risk in MC are not fully understood.
- Investigating mediator levels in active MC, MC in histological remission (HR), UC, and controls can elucidate disease-specific pathways.
Purpose of the Study:
- To compare the levels of secreted and cell-bound mediators in patients with active microscopic colitis (MC), MC in histological remission (HR), ulcerative colitis (UC), and healthy controls.
- To identify potential immunological differences that may explain the lower colorectal cancer risk in MC patients.
Main Methods:
- A Luminex assay was employed to measure the median fluorescence intensity of 54 analytes in colonic biopsies.
- Patient cohorts included active CC (n=21), active LC (n=11), UC (n=19), CC-HR (n=6), LC-HR (n=9), UC in remission (n=19), non-diarrhea controls (n=48), and diarrhea controls (n=25).
Main Results:
- Active CC showed higher Granzyme B and CCL5 levels than UC. MMP-1, MMP-3, and tumor necrosis factor receptor II were elevated in both CC and UC compared to controls.
- UC exhibited higher levels of APRIL, BAFF, BCMA, CCL20, CXCL8, chitinase 3-like 1, pentraxin-3, Fas, and IL-33 compared to MC.
- MC displayed lower increases in 4-1BB and perforin than UC, with decreased gp130 and IL-6Rα levels, while UC showed increased levels of these two analytes.
Conclusions:
- Microscopic colitis patients exhibit distinct immune mediator profiles, including elevated levels of analytes associated with CD8+ T lymphocytes, suggesting a different pathogenesis compared to UC.
- Elevated MMP-1 and MMP-3 levels in collagenous colitis compared to lymphocytic colitis support their classification as distinct disease entities.
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