Conference 2021 Live Talk
Altered Levels of immune checkpoint molecules in colon biopsies and sera from microscopic colitis and ulcerative colitis patients compared to controls
Authors and Affiliations
Alexandra Lushnikova1, Klas Sjöberg2, Andreas Münch3, Anna Lange4, Johan Bohr5, Olof Hultgren6 and Elisabeth Hultgren Hörnquist1
1. School of Medical Sciences, Örebro University, SE-701 82 Örebro, Sweden
2. Department of Gastroenterology, Skåne University Hospital, SE-205 02 Malmö, Sweden
3. Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health Science, Linköpings University, SE-581 83 Linköping, Sweden
4. Department of Infectious Diseases, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden.
5. Department of Medicine, Örebro University Hospital, Örebro University, Örebro, Sweden.
6. Department of Clinical Immunology and Transfusion Medicine, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden.
Microscopic colitis (MC) is an inflammatory bowel disorder that predominantly affects older individuals and is characterised by chronic, watery, non-bloody diarrhoea. To date, the aetiology is largely unknown and the two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC) present in a similar way. Patients with ulcerative colitis (UC), considered a classic form of inflammatory bowel disease (IBD), are at increased risk of developing colorectal cancer whereas no such association has been found in MC patients.
The reasons for this are yet to be identified and research in this area remains insufficient. Our hypothesis is that the immune response in MC is geared more towards immune surveillance of tumour cells than that of IBD, which instead contributes to inflammation-associated colon cancer.
Using Luminex, analysis of protein levels of 14 immune checkpoints (TIM-3, CD28, CD137, CD27, CD152, HVEM, IDO, LAG-3, BTLA, GITR, CD80, PD-1, PD-L1, PD-L2) in protein lysate samples from colonic biopsies from 62 patients (controls, n = 9; diarrhoea controls, n = 7; LC, n = 14; CC, n = 15; UC, n = 17) was performed. Soluble forms of these checkpoints were also analysed in serum from 89 patients, including 23 controls, 17 LC, 36 CC and 2 UC.
In LC and CC patients with active disease, levels of CD137, IDO, and CD80 were increased compared with one or both of the control groups. Levels of CD152 and PD-1 were increased in CC patients with active disease compared with both control groups. In UC patients with active disease, levels of CD137, CD152, BTLA, PD-1, and PD-L2 were increased compared with both control groups. Additionally, also in patients with active UC, levels of IDO were increased compared with controls, and an increase in CD80 was seen compared with diarrhoea controls.
In contrast, in serum samples, levels of CD27, IDO, CD80, PD-1, and PD-L2 were significantly decreased in LC patients compared to controls.
The increased concentrations of immune checkpoint molecules in colonic biopsies from UC and MC patients are likely a sign of inflammation and may indicate what kind of homeostatic feed-back mechanisms are active to balance inflammation. The lowered concentrations of soluble immune checkpoint molecules in sera from patients with lymphocytic colitis indicate a different level of homeostatic balance systemically in LC patients versus controls.