Immune response in inflammatory rheumatic diseases

Professor Patrick McNeil

Patrick McNeil has longstanding research programs in mast cell biology and innate immune responses in inflammatory rheumatic diseases, specifically rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) with three areas of focus during 2007. The first studied the role of tryptases in RA, and in a related project involving Dr John Hunt pursued ongoing characterization of two novel human tryptases, delta tryptase and splice variants of most human tryptase genes. In 2007, Prof McNeil undertook a sabbatical with his collaborators in Boston where he showed that mice deficient in the tryptase, mouse mast cell protease-6 (mMCP6) have less severe experimental arthritis than normal mice. This work was published in Arthritis and Rheumatism and suggests inhibition of mast cell tryptase may reduce arthritis severity in patients with RA. Prof McNeil also authored an invited mini-review in Journal of Biological Chemistry on mast cell tryptases in host defence. The second research area, in collaboration with Dr Nicodemus Tedla has been studying the role of the leukocyte immunoglobulin-like receptor (LILR) family of cellular activation/inhibition molecules in patients with RA, and we published in Rheumatology evidence that LILRs are down-regulated in RA synovium following treatment of the condition. The third area has focused on emerging evidence of common cellular pathways in RA and atherogenesis, with recognition that RA is an independent risk factor for cardiovascular disease, similar to diabetes. This work has occurred in collaboration with Professor Carolyn Geczy. Initial work investigated the role of acute phase reactants (C-reactive protein and serum amyloid A protein) as inducers of procoagulant activity on monocytes, and in 2007 we published in the Journal of Immunology evidence that serum amyloid A protein is a potent inducer of monocyte tissue factor. Ongoing work is focused on S-100 protein responses in RA.