Short summary

In the study we aim and try to prove that immunosuppressive peptide derived from HERV-H env59 is capable of lowering ex-vivo IL-6 expression in immune cells isolated in blood samples from acute moderate to severe ulcerative colitis. 

Rationale

The following proposal concerns the study of a putative advantageous role of a peptide derived from an endogenous retroviral envelope protein in inflammatory bowel disease (IBD). The Envelope 59 is a HERV-H derived envelope and is one of only three to constitute a complete open reading frame among over 100 HERV-H derived sequences in the human genome. Genetics, functional expression and immunological lines of evidence suggest a role for this protein in controlling the adverse effects associated with Systemic Lupus Erythematous (SLE). Based on that finding an anti-inflammatory peptide was synthesized and shown to have a protective effect in a murine rheumatoid arthritis (RA) model. Furthermore, the peptide can modulate the inflammatory state of cells isolated from blood samples from SLE and RA patients. We now want to investigate if a similar effect can be exerted on cells isolated from blood samples obtained from IBD patients, in particular in patients with active ulcerative colitis. If this is the case, we can hopefully show that patients with IBD in due time may benefit from treatment with this anti-inflammatory peptide. 

Description of the cohort

We aim for 20 patients with acute moderate to severe colitis ulcerosa. Inclusion criteria for acute patients:

1. Age over 18 years

2. Verbal and written acceptance of participation in the research project

3. Patient with established ulcerative colitis (clinical, endoscopic, histological evidence of ulcerative
colitis)

4. Diagnosis of ulcerative colitis for more than three months

5. Moderate to severe ulcerative colitis

6. Need for treatment with glucocorticoids

Furthermore, we aim for 20 patients with colitis ulcerosa in remission.

Inclusion criteria for patients in remission:

1. Age over 18 years

2. Verbal and written acceptance of participation in the research project

3. Patient with established ulcerative colitis (clinical, endoscopic, histological evidence of ulcerative colitis)

4. Diagnosis of ulcerative colitis for more than three months

5. Disease in remission

A.    No clinical disease activity

B.    Normal fecal calprotectin or normal endoscopy

Exclusion criteria:

1. Known or suspected Crohn's disease

2. Pregnancy and lactation

3. Invasive/systemic infection with fever

4. Already ongoing oral or intravenous glucocorticoid treatment (except local administered
treatment).

5. Ongoing antibiotic therapy

6. Ongoing treatment with azathioprine or 6-mercaptopurine (or other immunosuppressive drugs for
other indications than ulcerative colitis)

7. Ongoing treatment with biological therapy (i.e. TNF-inhibitors, inhibitors of integrins, inhibitors of
IL-12/IL-23)

8. Inability to speak or understand Danish language

9. Ongoing malignant disease

10.          Legally incompetence

We'll include 10 healthy controls without any chronic disease or daily medicine.

Data and biological material

Blood samples to analyse expression of IL-6 or related cytokines.

Data from patients' medical journals: Basic patient-demographic like age and gender as well as disease duration, previous treatment etc.

Collaborating researchers and departments

Department of Medical Gastrointestinal Diseases, Odense University Hospital

• Professor, Jens Kjeldsen, PhD

Institute of Molecular Medicine, University of Southern Denmark

• Lector, Jonas Heilskov Graversen, PhD

Department of Rheumatology, Aarhus University Hospital

• Lector, Magdalena Janina Laska, PhD

University of Southern Denmark

• Stud. Med., Sune Hansen
• Stud. Med., Johan Christian Lund

Publications associated with the project

1.                       Bahrami S, Gryz EA, Graversen JH, Troldborg A, Stengaard Pedersen K, Laska MJ. Immunomodulating peptides derived from different human endogenous retroviruses (HERVs) show dissimilar impact on pathogenesis of a multiple sclerosis animal disease model. Clinical immunology (Orlando, Fla). 2018;191:37-43.

2.                       Laska MJ, Troldborg A, Hauge EM, Bahrami S, Stengaard-Pedersen K. Human Endogenous Retroviral Genetic Element With Immunosuppressive Activity in Both Human Autoimmune Diseases and Experimental Arthritis. Arthritis & rheumatology (Hoboken, NJ). 2017;69(2):398-409.