Year of grant:
Heilsa - Sjúkrakassagrunnurin
Characterizing the immune cell response in HLA-B27(-) Spondyloarthritis
Amanda Gratton Vang
Pero Soré, Nicolina Ovadóttir Vest, Anna Sofía Veyhe, Arnfinnur Kallsberg
Grant from the FRC in DKK:
This is a disease-based study focusing on current Spondyloarthritis (SpA) patients. SpA is a group of inflammatory rheumatic disorders with a two-fold higher prevalence than rheumatoid arthritis in the general population. The HLA-B27 allele is strongly associated with Spondyloarthritis (SpA), however, HLA-B27 is not necessary for development of SpA. This project aims to compare the functional immune response in HLA-B27 carriers and non-carriers with SpA based on the hypothesis that the presence or absence of HLA-B27 drives variation in circulating immune cells function but produces similar clinical disease. The long-range application of these results is to expand the clinical tools available to manage and track SpA, especially in HLA-B27(-) individuals where disease development isn’t well defined. The overlap of SpA with other immune-related diseases speaks to the complex pathogenesis of SpA and the difficulties in achieving an accurate diagnosis and effective treatment. This study represents the first functional analysis of immune cell responsiveness within the Faroese population. In addition, it will serve as the pilot project to establish a flow cytometry facility within the Department of Medicine at the National Hospital of the Faroe Islands with the vision of expanding the biomedical research program and facilitating international collaboration.
In 2017 we retrospectively identified 287 individuals via xray requisition and review of rheumatology clinical notes which indicated a suspicion of Spondyloarthritis (SpA). We then further refined the group by cross-referencing with prescriptions for disease modifying anti-rheumati drugs. 154 patients fulfilled the criteria of receiving an xray or MRI of the sacroilliac joints, a perscription of a DMARD, and clinical note of SpA-related symptoms. The cohort was 52,6% female, 47,6% male). SpA without clinical definition was the predominant subtype 42,2% followed by PsA 27,7%, AS 14,4% which was strongly skewed towards men, SpA-IBD 8%, undifferentiated SpA 6,5% and Juvenile Artritis 2,6%. Women accounting for a larger proportion subtypes with extra-articular manifestations. Data allowance was given for this registry study and there was no patient contact. This is the first estimate of SpA occurance on the Faroe Islands and underscores the need for a combined longitudinal registry that tracks multiple inflammatory/immune-mediated diagnoses. In order to work further with this cohort, individuals would need to be contacted and characterized using standardized research critera for disease symptoms.
We also established infastructure and workflows for flow cytometry which is a conerstone of investigating inflammatory responses in diseases like SpA. We now have standard operating procedures in place for isolating populations enriched for CD4+ T cells from whole blood, monitoring major immune cell groups (T cells, monocytes, granulocytes, etc) and integrin markers of activation.
The two parts of this project resulted in the successful completion of a Masters Thesis and a Bachelor Thesis at the University of the Faroe Islands:
Masters Degree in Public Health, Fróðskaparsetrið June 20th, 2019 to Erla Nielsen
Bachelor of Science in Molecular Life Sciences, Fróðskaparsetrið Award August 1st, 2019 to Arnfinnur Kallsberg