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Contact Details

Phone
64 3 474 0999 ext 58508
Email
paul.hessian@otago.ac.nz
Position
Senior Research Fellow
Department
Department of Medicine (Dunedin)
Qualifications
BSc(Hons) PhD(Otago)
Research summary
Macrophages and adhesion molecules in inflammation

Research

Research in the Leukocyte and Inflammation Research Laboratory focuses on human inflammation biology. The laboratory uses a range of specialist research techniques that span the broad topics of cell biology, biochemistry and molecular biology.

The rheumatoid nodule appears in rheumatoid arthritis patients with the worst disease. Found in subcutaneous sites, and also on the lungs and heart valves, a nodule is a granulomatous lesion, typified by a necrotic centre that is surrounded by a palisading layer of inflammatory monocyte/macrophages. T-lymphocytes and dendritic cells are also present. We have compared this lesion with the joint synovial lesion more commonly associated with RA. The range of proinflammatory and chemotactic cytokines within each lesion is remarkably similar as are the cell populations with the exception that B-lymphocytes are present in inflamed synovium but not the nodule lesion.

We are continuing to characterise the inflammatory milieu of the rheumatoid lesions and have recently expanded the scope of this approach using microarray analysis. Of particular interest are the immune/inflammatory components that initiate and maintain the formation of ectopic lymphoid follicles in the joint synovium. These follicles reflect the presence of follicular dendritic cells (FDC) within the joint. The FDC, even in early stages of follicle development, may provide an indication of the potential for joint damage in patients with early RA. Follicles do not occur in rheumatoid nodules. Follicles and there influence on outcome of rheumatoid arthritis is a topic of research recently funded by the Health Research Council of New Zealand.

The S100 calcium-binding proteins have been implicated as important to a number of inflammatory situations. We continue to work on two members of this family, named S100A8 (or MRP-8) and S100A9 (MRP-14). These two proteins form a heterodimeric complex present in large amounts in the cytosol of monocytes and neutrophils. In human systems, separated S100A9 activates the integrin adhesion molecule, Mac-1, a function consistent with a role for the S100 proteins in inflammation. Current work focuses on how S100A8 and S100A9 mediate any biological effect and particularly the role of RAGE (receptor for advanced glycation end products) as a possible receptor. Detailed analysis of the N-linked glycosylation pattern of RAGE and of modifications to the carbohydratecould provide clues as to how this ligand-receptor axis operates in inflammation.

Publications

Stamp, L. K., Keating, P., Frampton, C., Barclay, M. L., Fanning, N., Millier, M., Hessian, P. A., & O'Donnell, J. L. (2024). Relationship between adalimumab concentrations, anti-drug antibodies and disease activity in rheumatoid arthritis: A cross-sectional observational study. Journal of Rheumatology, 51(3), 242-249. doi: 10.3899/jrheum.2023-0706 Journal - Research Article

Wiles, A. K., Mehta, S., Millier, M., Woolley, A. G., Li, K., Parker, K., Kazantseva, M., Wilson, M., Young, K., Bowie, S., Ray, S., Slatter, T. L., Stamp, L. K., Hessian, P. A., & Braithwaite, A. W. (2023). Activated CD90/Thy-1 fibroblasts co-express the Δ133p53β isoform and are associated with highly inflamed rheumatoid arthritis. Arthritis Research & Therapy, 25, 62. doi: 10.1186/s13075-023-03040-8 Journal - Research Article

Millier, M. J., Fanning, N. C., Frampton, C., Stamp, L. K., & Hessian, P. A. (2022). Plasma interleukin-23 and circulating IL-17A(+)IFNγ(+) ex-Th17 cells predict opposing outcomes of anti-TNF therapy in rheumatoid arthritis. Arthritis Research & Therapy, 24, 57. doi: 10.1186/s13075-022-02748-3 Journal - Research Article

Millier, M. J., Lazaro, K., Stamp, L. K., & Hessian, P. A. (2020). The contribution from interleukin-27 towards rheumatoid inflammation: Insights from gene expression. Genes & Immunity, 21, 249-259. doi: 10.1038/s41435-020-0102-z Journal - Research Article

Stamp, L., Keating, P., Frampton, C., Barclay, M., Fanning, N., Millier, M., Hessian, P., & O'Donnell, J. (2019). Relationship between adalimumab concentrations, plasma cytokines, anti-drug antibodies and disease activity in rheumatoid arthritis. Arthritis & Rheumatology, 71(Suppl. 10), 1440. doi: 10.1002/art.41108 Conference Contribution - Published proceedings: Abstract

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