Using autoantibodies as a sub-classification tool in SSC

Thursday, 20 Aug 2015

In the first of a series of articles profiling rheumatology researchers we speak to Jenny Walker from the Repatriation General Hospital in Adelaide on her search for a biochemical marker that reflects disease activity in scleroderma.

What’s the issue your research is trying to solve?

Newer technologies have allowed a number of the rarer auto antibodies (AA) associated with scleroderma to be tested in routine diagnostic practice. We don’t know whether wider availability of these AAs will improve classification of systemic sclerosis (SSc). We were interested in exploring the clinical associations of the scleroderma-associated autoantibodies in a well characterised australian scleroderma cohort.

What have you discovered so far?

The majority of scleroderma patients were positive for one of the three major scleroderma associated autoantibodies (RNA polymerase III, SCL-70 and anti-centromere antibody) but co-expression of autoantibodies was common.

We utilised a principal components analysis  to explore relationships between autoantibodies and found that most of the variation in expression could be explained by 5 major clusters, corresponding to the dominant presence of one of the three major scleroderma associated autoantibodies (anti-centromere antibody, anti-SCL70 antibody, anti-RNA polymerase III antibody (high and low expression)) and one other group.

When we compared these groups with the clinical data, we found strong clinical associations. In this Australian cohort, sub classifying patients on the basis of the three major scleroderma AAs alone, independent of clinical assessment, identified different clinical cohorts with strong clinical associations. This has clinical implications particularly in early disease when skin involvement may not yet reflect the disease subtype.

While the rarer scleroderma associated autoantibodies, such as anti-fibrillarin and anti TH/TO, may have benefit in specific clinical settings, results from our cohort of 505 patients must be interpreted with caution. Multinational studies will be necessary to clarify the disease associations of these rarer antibody subsets.

What’s been your biggest hurdle?

Not so much a hurdle as a challenge. Rare diseases really benefit from disease registries and this study required input from a large number of clinicians and other researchers as well as the patients who have generously contributed their time to the Australian Scleroderma Cohort Study. Bringing all this information together is a huge and constantly evolving challenge, and something that we are all involved in.

How far is your work from impacting patient care?

I hope that our findings will encourage others to consider the use of autoantibodies alone as a sub classification tool, particularly in early disease, where prognostication and early treatment decisions, especially in the setting of clinical trials, may become important.

If you could discover one thing in your area of research, what would it be? (e.g what’s your holy grail?)

It would be nice to find a biochemical marker that reflects disease activity in scleroderma and can be used in routine clinical practice to monitor responses to treatment.

About the researcher: Jenny Walker is a senior staff specialist in Rheumatology at Flinders Medical Centre.  Her major research interest is scleroderma and she completed a postdoctoral research and clinical fellowship with the Canadian Scleroderma Research Group and the University of Calgary in 2007 before returning to Australia.  She is a member of the Australia Scleroderma Interest Group and in addition to her research interests, continues an active clinical practice.

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