Short summary

The primary aim of this prospective cohort study is to investigate the prognostic value of the ratio between high molecular weight (HMW) and low molecular weight (LMW) of Surfactant protein D (SP-D) molekyles in Chronic inflammatory diseases (CID) patients predicting who will respond to therapy based on both disease-specific and generic treatment outcomes. Secondary aims are to investigate if the ratio between HMW and LMW differs between each CID and if the ratio correlate with disease activity.

Rationale

Chronic inflammatory diseases (CIDs) are a diverse set of immunologic diseases that include inflammatory bowel disease (IBD) (Crohn's disease [CD] and ulcerative colitis [UC]), rheumatic conditions (rheumatoid arthritis [RA], axial spondyloarthropathy [axSpA], psoriatic arthritis [PsA]) and inflammatory skin diseases (psoriasis [PsO]). Pro-inflammatory cytokine as tumour necrosis factor α (TNF) is recognized to play an important role in the aetiology of these diseases. Correspondingly, biological agents inhibiting these cytokines are important in the treatment. Surfactant protein-D (SP-D) belongs to the collectin family of the innate immune system and acts by regulating the immune response as a soluble pattern recognition receptor. SP-D is mainly expressed and secreted by pulmonary type II alveolar cells and Clara cells but has also been reported on additional epithelial surfaces including the vascular endothelium. The mature SP-D monomer structure consists of 4 structural domains, 1) the N-terminal domain involved in the disulfide crosslinking between SP-D molecules, 2) a collagen domain important for spacing of the C-type lectin domains (CTLD), 3) an α-helical neck region involved in protein trimerization, and 4) a globular C-terminal CTLD, responsible for the Ca2+-dependent binding of microbial ligands. The protein structure is stabilized through assembly into trimers and multimers via two cysteine residues in the N-terminal domain. The distribution of the low molecular weight (LMW) trimeric units of SP-D and high molecular weight (HMW) multimer in serum depend on genetic variation within the SP-D (SFTPD) gene, primarily on a single nucleotide polymorphism (SNP) rs721917 . The primary effect of SP-D is the aggregation and enhancement of the phagocytosis by binding to pathogens, saccharides, lipids and nucleic acids. In addition, SP-D exerts anti-inflammatory activities by supporting the clearance of apoptotic cells and DNA and by enhancing uptake and presentation of antigens by dendritic cells, and thereby initiates an adaptive immune response. SP-D in serum comprises both high and low molecular oligomeric variants characterized by different biologic properties including pro- and anti-inflammatory effects. Low protein concentrations, genetic variation, biochemical modification and proteolytic degradation induce the decomposition of multimeric SP-D into trimeric SP-D, and the latter forms might infer pro-inflammatory SP-D signalling.

Description of the cohort

The BELIEVE study is a prospective multicenter cohort study of 230 CID patients planned to start treatment with a biologic disease-modifying drug over a three-year period from September 21, 2017 to March 30, 2020. Patients are recruited from: Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark. Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark. University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark. Department of Gastroenterology, Slagelse Hospital, Slagelse, Denmark. Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. Department of Surgery, University Hospital of Southern Denmark, Aabenraa, Denmark. Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Department of Gastroenterology, Hospital of Southwest Jutland, Esbjerg, Denmark.

Data and biological material

The BELIEVE study is performed and a biobank including blood samples is established. Clinical data include personal data, data on health and disease, dietary and non-dietary lifestyle information, laboratory measurements, and disease activity scores including patient-reported outcome measures (PROMs), clinical assessments, and laboratory data. Participants complete validated questionnaires on disease activity, quality of life and lifestyle using an electronic link (REDCap).

Collaborating researchers and departments

Professor, Cand. scient Grith Lykke Sørensen, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.