Autoimmune disease

Autoimmune diseases are caused when the bodies own immune system mistakingly attacks its own tissues, for example the insulin-producing cells of the pancreas in childhood (type 1) diabetes, and the synovium tissue that lines the joint in rheumatoid arthritis. These diseases have shared causes, with some differences. World-wide genetic studies have shown that a central cause of autoimmunity is a dysregulated immune system, particularly T-cells. The environment plays a role, with smoking doubling the risk of rheumatoid arthritis, and vitamin D deficiency increasing the risk of type 1 diabetes by up to 50 percent.

Our research

We are taking a genetic approach to the understanding of the biological causes of autoimmunity. We are comparing the frequency of genetic variants that we think cause gout between people with and without autoimmunity. More recently our research has focussed on rheumatoid arthritis and inflammatory bowel disease (in collaboration with Dr Rebecca Roberts), previously on type 1 diabetes. Please see below for our publications, including a lay explanation of the results. We thank all those people who have generously donated samples for this research.

Our results in rheumatoid arthritis

Hollis-Moffatt JE, Chen-Xu M, Topless R, Dalbeth N, Gow PJ, Harrison AA, Highton J, Jones PBB, Nissen M, Smith MD, van Rij A, Jones GT, Stamp LK, Merriman TR (2010) Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: Confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance Arthritis Res Ther 12:R116 PubMed Explanation: The interleukin-21 gene is one gene that controls 'Th17 cells', a subset of T-cells very important in rheumatoid arthritis. We confirmed at a rigorous statistical level that this gene plays a role in rheumatoid arthritis. Our analysis also suggested that the exact nature of the association at this gene influences the type of autoimmune disease to which a person is susceptible.

Hollis-Moffatt JE, Merriman ME, Rodger RA, Rowley KA, Chapman PT, Dalbeth N, Gow PJ, Harrison AA, Highton J, Jones PBB, O’Donnell JL, Stamp LK, Merriman TR (2009) Evidence for association of an interleukin-23 receptor variant independent of the R381Q variant with rheumatoid arthritis. Ann Rheum Disease 68:1340-4. PubMed Explanation: The interleukin-23R gene is another gene that controls 'Th17 cells', important in T-cells. There are a number of different genetic variants in interleukin-23R involved in different autoimmune diseases. This is the first time that one of these genetic variants have been implicated in rheumatoid arthritis. However, it is important that other research groups confirm our results.

Phipps-Green A, McKinney C, Rossol M, Merriman ME, Topless R, Hollis-Moffatt JE, Wan Taib WR, Dalbeth N, Gow PJ, Harrison AA, Highton J, Jones PBB, Stamp LK, Wagner U, Wordsworth P, Merriman TR (2011) Analysis of association of DNASE2 promoter variation with rheumatoid arthritis in European Caucasians. Supplemental Table