Canadian Scleroderma Research Group

Background

The Canadian Scleroderma Research Group (CSRG) was established in 2004 with grants from the CIHR, industry and Canadian patient societies. Fifteen rheumatologists across Canada have, at one time or another, recruited patients into the registry. We now have data on 1753 patients, some with up to 13 years of follow up, and we collect 1543 variables. We initially saw all patients, with both new and established disease, yearly. However, several years ago, we decided to follow patients up to 10 years of disease duration. This plan was meant to save costs and to focus on the disease during earlier, more informative years. Indeed, early disease has become a new focus for our research cohort. Some sites that participated at the onset of the CSRG have dropped out for various reasons, including the death of a recruiting physician with no one to replace her, retirement, lack of local resources to cover the costs of the nurse needed for the study visits, and change in the focus of the participating physician. On the other hand, we have gained new sites, such as Quebec City.

In 2013, a new set of classification criteria was published on behalf of the American College of Rheumatology and the European League Against Rheumatism.  The committee consisted of four North American and four European experts.  Drs Murray Baron and Janet Pope, who have recruited the most patients into the CSRG, were two of the four North American experts on the committee, attesting to the Canadian leadership in scleroderma research. Moreover, the CSRG dataset was widely used in the development and validation of these criteria, which have now become the gold standard in the field.

The CSRG has published 135 papers using data from the CSRG database. Our publications in the last 10 years constitute 2.2% of all the world’s scleroderma publications during that period of time.  This is a remarkable output for one organization. A booklet with the cover pages of most of our publications has been distributed separately and another copy is available upon request.

The CSRG has become a world leader in scleroderma research. In turn, the reputation of our researchers has soared because of the CSRG. Dr. Baron was president (2015 – 2017), and is currently an active member of the executive committee, of the Scleroderma Clinical Trials Consortium which represents the majority of researchers and clinicians in the world with an interest and expertise in the care of, and research in, scleroderma. He also serves on the editorial board of the Journal of Scleroderma and Related Disorders and previously served as chair of the American College of Rheumatology Scleroderma Abstract Selection Committee. In recent years, he created and directs the International Systemic Sclerosis Inception Cohort (INSYNC). This is an international group of researchers that has agreed to use a common dataset and to share data to pursue research specifically in early scleroderma. International collaborations are essential in rare diseases such as scleroderma, even more so when the focus is on new onset cases. To date, INSYNC includes sites in Canada, Australia, Netherlands, Spain, Germany, Brazil, United States, and Sweden. Of particular note, INSYNC depends entirely on the CSRG infrastructure for administrative and statistical support. Using foundational work generated from the CSRG dataset, Dr Brett Thombs obtained a large CIHR grant to create the Scleroderma Patient-centered Interventional Network (SPIN), an international cohort established to develop and test psychosocial and rehabilitative interventions to improve the health-related quality of life of people living with scleroderma. So far, he has recruited about 2000 patients and has launched studies to investigate …(self-management, hand function, depression). 

Dr Marie Hudson, who is the only fulltime academic rheumatologist working on the CSRG data, is now internationally recognized for her scleroderma research.  Among other international commitments, she currently directs the Tri-Nation (Canada, Australia, Houston) Scleroderma cohort, leads the Scleroderma Clinical Trials Consortium Working Group on Scleroderma Renal Crisis, is Co-Chair of the American College of Rheumatology Scleroderma Abstract Selection Committee and sits on the editorial board of the Journal of Scleroderma and Related Disorders.

Current Ongoing and Future Studies

The following is a list and descriptions of 30 ongoing and future studies, as well as four laboratory projects. This list is ever expanding as the findings of these projects often lead researchers to new and more nuanced questions. The limitations to this research- into better ways to diagnose and treat scleroderma, and improve patient quality of life- are related entirely to the scarcity of funding. Many of these projects are unfunded which in reality means researchers, physicians, and support staff, carry them out without being compensated and on their own time.

Lung Symptoms

Do immunosuppressive drugs prevent the development of lung disease in scleroderma? Dr Sabrina Hoa, Master in Epidemiology (McGill), funded by The Arthritis Society Post-doctoral award, is trying to answer this question in her thesis. Her results look very promising. 

Pulmonary Function Tests as Surrogate Markers for Interstitial Lung Disease Progression in Systemic Sclerosis. Funded by a CIHR doctoral award, Melissa Caron from McGill is examining the trajectories of lung disease in scleroderma, how should we measure them best and what predicts them. It is important to understand this to be able to decide who should be treated and when.

The risk of HRCT scans on the development of lung cancer in scleroderma.

Lung cancer occurs more often in scleroderma than in the general population. Does frequent use of lung scans contribute to this? Mohamed Mansour, a McGill medical student, has been funded by a Faculty of Medicine bursary to pursue this project. 

Treatment of interstitial lung disease in subjects excluded by clinical trials. To date, there have been 3 randomized clinical trials for SSc subjects with interstitial lung disease. All 3 have selected patients with early disease with at least moderate lung disease (FVC < 85%). However, the vast majority of patients with interstitial lung disease in the CSRG cohort have more longstanding and/or milder lung impairment. There is no data available on the benefits of treatment in these 2 subsets of patients. Dr Sabrina Hoa, Master in Epidemiology (McGill), funded by The Arthritis Society Post-doctoral award, will also address this question in her thesis.

Gastro-Intestinal Symptoms

Can Small Intestinal Bacterial Overgrowth (SIBO) be diagnosed and treated more efficiently?  SIBO is a frequent and serious complication of scleroderma where bacteria grow in the bowel because the bowel slows down in scleroderma. We have been funded by the CIHR to do an international study to test if a very strict protocol to treat this will help our patients more than usual care. The funds awarded are actually small (about $200,000) and we need to find additional financial resources to complete the study successfully.

Do immunosuppressive drugs prevent the development of severe gastrointestinal disease?  This is another project we are leading with other INSYNC sites.

Is severe gastrointestinal disease in early scleroderma associated with an increased risk of mortality? We are leading this project and working in collaboration with other INSYNC sites including Australia, Spain, the Netherlands, and the United States.

Skin Symptoms

The role of WNT signaling in the pathophysiology of calcinosis.

Treatment of calcinosis is one of the most serious unmet needs in scleroderma. We have developed a new collaboration with Drs Adel Schwertani (McGill) and Louis-Georges Ste-Marie (University of Montreal) to study samples of calcinosis to understand what metabolic pathways are involved. This could give us important clues on how to treat this.

Calcinosis

In addition to understanding mechanisms contributing to calcinosis, we must also be able to measure this problem so that the efficacy of potential treatments can be tested. We developed a way to use x-rays of the hands to score the amount of calcium deposited there and are now participating in an international study of the course of calcinosis. We will be testing a new patient reported questionnaire assessing the effect of calcinosis on their lives and will also test the ability of the x-ray score to detect changes over time.

The predictive value of skin involvement

Does the extent of skin involvement allow us to predict future organ damage and quality of life in early diffuse cutaneous systemic sclerosis? Drug approval agencies want to know if drug studies that use the changes in skin as the main outcome of the trial can expect that internal organ changes mirror the skin changes.  We are doing a large study using our data to look at this.

Systematic review of the role of ultrasound to measure skin fibrosis in scleroderma.

Skin is usually scored based on a physical exam by the doctor. Could there be a better way to do this?  We are reviewing the world literature to see if ultrasound would be a more objective measure. Dr Meriem Kerbachi, PGY5 (McGill), is involved in this project.

Renal Symptoms

Development of classification criteria for scleroderma renal crisis.

Funded by the Scleroderma Clinical Trials Consortium ($12,000 USD), Dr Marie Hudson is leading an international group of experts to develop consensus- and data-driven classification criteria for scleroderma renal crisis. This should facilitate future research into this rare but life-threatening complication of SSc, for which there is an urgent need to identify novel therapeutic options.

Genetics of scleroderma renal crisis (SRC)

The CSRG has been asked to participate in an international study led by Dr John Varga of Northwestern University (Chicago) to identify genetic markers that are associated with SRC. This may help us understand the pathophysiology of this complication as well as identify novel therapeutic targets. The CSRG will contribute approximately 40 cases and 80 controls.

Activation of mammalian target of rapamycin in renal tissue of patients with scleroderma renal crisis: a hypothesis-testing study

Scleroderma patients can develop severe high blood pressure and kidney failure. We want to better understand why this happens. This could also help us find new treatments for this serious complication. Dr Jessica Salturi, PGY2 at McGill, submitted an abstract summarizing preliminary results for the 2018 Canadian Rheumatology Association annual meeting. 

Cardiac Symptoms

Electrocardiograms in scleroderma. How do we know if the heart is involved in scleroderma? This is a very difficult question. We have examined 1000 electrocardiograms (ECGs) from our patients and another 1000 from controls to see what abnormalities may be specific to scleroderma. Dr Sophie Wojcik, PGY5 (McGill), submitted an abstract summarizing some of this work for the 2018 Canadian Rheumatology Association annual meeting.

How to define heart disease in scleroderma? 

We initiated and are part of a working group of the Scleroderma Clinical Trials Consortium created to define heart involvement in scleroderma. CSRG data will be used extensively for this project.

Systematic review of EKG abnormalities in Scleroderma.

Dr Stephanie Kelly, PGY1 (Northwestern University, Chicago) has undertaken this project. A systematic review is a very rigorous way of reviewing the world’s scientific literature. It is very time consuming but is the best way to put together a lot of different studies together and to make robust conclusions. This is being done as part of our interest in finding out what ECG abnormalities really are associated with the disease.

Evidence-based guidelines for screening for pulmonary arterial hypertension in SSc.

Guidelines recommend yearly cardiac echocardiography to screen SSc patients for pulmonary arterial hypertension. However, there is little evidence to support this and in fact this is probably not needed in patients at very low risk. We are in the process of developing an algorithm using symptoms and pulmonary function tests to identify patients at very low risk who may not need yearly echocardiography. This has the potential to save precious resources and reduce health care costs by eliminating unnecessary testing. This project involved Teresa Semalulu, a medical student from the University of Northern Ontario, who was funded by a Canadian Rheumatology Association summer studentship. In addition, Roche Inc has provided in-kind funding worth approximately $40,000 to test whether a blood test, NT-proBNP, adds to the predictive ability of the algorithm.

Miscellaneous Symptoms

Trigeminal neuralgia in scleroderma – clinical and serological associations. One of the facial nerves is sometimes affected by scleroderma.  We are looking at how this relates to the rest of the disease. Dr Nancy Maltez, PGY5 (University of Ottawa), will be presenting an abstract on our findings at the American College of Rheumatology meeting in San Diego in November 2017.

The spectrum of myopathy in scleroderma– clinical and serological associations

Inflammation in muscle occurs in scleroderma. We want to describe this more carefully to help determine why this happens and how to treat it. Dr Teresa Carfaro, PGY4 (McGill), presented preliminary results at the 2017 Canadian Rheumatology Association annual meeting, and is now preparing a more detailed manuscript.

Biomarkers, Assessment Tools, and Scales

Do immunosuppressive drugs affect the CRISS? The American College of Rheumatology Provisional Composite Response Index for Clinical Trials (CRISS) is a new way of measuring patient outcomes in drug trials. We participated in its development and are now doing a study using the CSRG database to see if we can tell if the use of drugs that suppress the immune system lead to patient improvement based on the CRISS.

Validation of the Scleroderma Clinical Trials Consortium Damage Index. 

With members of INSYNC, we led a team that developed a totally new way to measure scleroderma. The disease leads to damage in many organs but there has not been a way to measure that overall damage.  We have developed the Scleroderma Damage Index, which does just that.  This can be used in drug trials to see if a drug prevents the accumulation of damage.  We are now testing this in our database to see how well it performs.

Disease Activity Index. 

The same group that developed a damage index is now just starting to work n a disease activity index.  We assume that the disease process may have times when it is active and others when it is quiet.  We do not know how to tell when it is active.  That is important because that may be the time to use medications that may do nothing when the disease is quiet.

PRESCIENCE – PREcision medicine in SCleroderma using Cellular Epigenomics.

There is an urgent need to accurately predict disease progression in SSc,to avoid exposing patients to drugs with possible toxicity if their risk of progression is low and to optimize the use of new, expensive treatments. Dr Marie Hudson recently submitted a grant to CIHR to studythemethylomes of a suite of disease-relevant cell typesin aprospective, treatment-naïve cohort of SSc patients followed longitudinally, to identify biomarkers of disease progression andthereby personalize treatment decision-making in SSc.A funding decision is expected for early 2018.

Autoantibodies

Tri-nation Scleroderma Cohort

This cohort is composed of the CSRG, GENISOS, an NIH-funded study based in Houston, Texas, and the Australian Scleroderma Interest Group. This collaboration was undertaken to study the clinical correlates of some of the less frequent autoantibodies found in systemic sclerosis. The harmonized dataset includes over 1500 subjects with detailed serologies using a common platform. We have already published 2 papers in high-impact journals using this dataset. We have 3 more studies underway. This work is unfunded but is highly dependent on the CSRG infrastructure (research coordination and statistical support).

Novel antibodies associated with cancer in scleroderma

A link between scleroderma and cancer has been identified in many studies, in particular in patients with anti-RNA polymerase III antibody positive patients. However, 2 fascinating papers published in the last year have also identified a higher risk in “triple negative” patients (those without anti-centromere, anti-topoisomerase and anti-RNA polymerase III antibodies). In those patients, about 25% had a novel antibody, anti-RNPC3. Other novel antibodies in “triple negative” patients therefore remain to be identified. In collaboration with Dr Marvin Fritzler, a world leader in antibody discovery at the University of Calgary, we are trying to identify some of these in the sera of CSRG patients who have and have not had cancer. These novel antibodies will allow us to identify patients at high risk of underlying malignancy, as well as shed new insights into mechanisms of disease.

Treatments

Stem Cell Transplants. 

In a quick informal survey we found that about 16 stem cell transplants have been performed in Canada as treatment for SSc. Recent studies show marked improvement after transplants in certain patients.  We expect the requests for this therapy to increase. We wish to develop a Canadian transplant agenda by bringing together patients, hematologists, rheumatologists and the authors of the large studies stem cell transplant studies with the aim of developing a national Scleroderma transplant network. We will develop a research program around it to study ways to make transplants safer for patients. We plan to study the cost-effectiveness of transplant in collaboration with Professor Mark Harrison, UBC. We also will study the changes in Health-related quality of life pre-post transplant (collaboration with Professor Dominique Farge, Paris; We submitted an application for funding mid-November 2017 to the CIHR ($40 000) with matched pledged funding from various provincial  patient Scleroderma societies (including Ontario, British Columbia, Saskatchewan, and Nova Scotia) and Fonds France-Canada pour la Recherche to fund trainees ($15,000).

Laboratory Projects

There are 4 researchers from 4 laboratories now interested in collaborative projects:

Dr Annie Philip, McGill University

Dr.Philip’s laboratory located at the Montreal General Hospital is well equipped to perform all cell biology and molecular biology techniques to continue her research on aberrant TGF-beta signaling in scleroderma. This is the main molecule that stimulates cells in the body to produce collagen that is what makes up most of the fibrosis or scarring found in scleroderma.  Her lab has access to state state-of-the art cell culture facility and tissue processing unit. Dr. Philip is a member of the Canadian Scleroderma Research Group (CSRG). Her current research focuses on the understanding the role of aberrant activation of TGF-beta signaling in scleroderma skin cells with a central focus on impairment of TGF-BETA receptor on the cell surfaces.  She requires skin biopsies’ for her projects.  Many types of skin cells are isolated from the biopsies and studied. Specific projects in the lab are centered on the studies of alterations in the regulation of distinct signaling pathways and their characterization.

Dr Marc Servant, Universite de Montreal

Dr Marc Servant is interested by the study of cellular signaling cascades controlling low-grade inflammatory reactions. Notably, as a recipient of a Canada Research Chair in Inflammatory Response Signaling, Dr. Servant is studying specific proteins (kinases and ubiquitin ligases) that regulate the innate immune and inflammatory responses to diseases such as atherosclerosis, virus infection and autoimmune disorders.  With the help of state-of-the-art cell biology techniques, genetics and equipment, his group of researchers aims to identify new biomarkers and cellular targets for diagnosis and treatment.  Blood cells and cells isolated from skin biopsies will be obtained from age-matched volunteers, SSc patients with the limited cutaneous subtype (limited disease) and those with the diffuse cutaneous subtype (diffuse disease). His lab will isolate RNA and proteins from the cells to assess the role of a specific pathway involving a protein called IKK-IRF5.  He hypothesizes that this is central to the fibrosis that occurs and may be a target for treatment as well as a biomarker of active disease.

Dr Mohit Kapoor, University of Toronto

Dr. Kapoor’s lab focuses on understanding cellular and molecular mechanisms associated with inflammation and fibrosis during various rheumatic diseases. His lab’s proposed project is the regulation and role of proteoglycans (PGs) in the pathogenesis of systemic Sclerosis. PGs are the other component of the matrix around cells other than collagen that is better known and which has been studied extensively in scleroderma. Patient’s with early diffuse cutaneous scleroderma with involvement of the cutaneous skin for < 6 months and who are not yet on any systemic treatment such as immunosuppressive medications or corticosteroids will have 6mm skin biopsies at participating CSRG sites. Each biopsy will be divided and processed under strict standard operating procedures for studies; fibroblast (the cells that cause fibrosis) isolation for cell culture studies; concentration of PG fragments in tissues; collagen Assays in tissues; gene expression studies.

Dr Andrew Leask, Western University

Dr Andrew Leask’s work has focused on the contribution of a set of proteins called Connective Tissue Growth Factor (CCN2/CTG) to the fibrosis process. He has published extensively on this subject and will do further studies in our patients. Although there has been a lot of work on the role of the protein TGF-bet in causing fibrosis, he is concentrating on another potentially important molecule that could lead to new drug targets. He has already found that CCN2 is necessary in animal models of fibrosis. Due to the translational nature of his work, he will back up the mouse work by data in which he tests his ideas out by comparing fibroblasts from healthy individuals and individuals with scleroderma. Thus these cells are essential to validate our ideas in a clinically relevant setting and will be the focus of his future work

Publications

In the past 2 years alone we have 26 publications, including many collaborations between the CSRG and other groups in the world. A comprehensive booklet of our publications has been provided to you in the past year. Additional copies can be provided if required.

1. Wu M, Baron M, Pedroza C, Salazar GA, Ying J, Charles J, Agarwal SK, Hudson M, Pope J, Zhou X, Reveille JD, Fritzler MJ, Mayes MD, Assassi S. CCL2 in the Circulation Predicts Long-Term Progression of Interstitial Lung Disease in Patients With Early Systemic Sclerosis: Data From Two Independent Cohorts. Arthritis & rheumatology (Hoboken, NJ) 2017;69:1871-8.
2. Terao C, Kawaguchi T, Dieude P, Varga J, Kuwana M, Hudson M, Kawaguchi Y, Matucci-Cerinic M, Ohmura K, Riemekasten G, Kawasaki A, Airo P, Horita T, Oka A, Hachulla E, Yoshifuji H, Caramaschi P, Hunzelmann N, Baron M, Atsumi T, Hassoun P, Torii T, Takahashi M, Tabara Y, Shimizu M, Tochimoto A, Ayuzawa N, Yanagida H, Furukawa H, Tohma S, Hasegawa M, Fujimoto M, Ishikawa O, Yamamoto T, Goto D, Asano Y, Jinnin M, Endo H, Takahashi H, Takehara K, Sato S, Ihn H, Raychaudhuri S, Liao K, Gregersen P, Tsuchiya N, Riccieri V, Melchers I, Valentini G, Cauvet A, Martinez M, Mimori T, Matsuda F, Allanore Y. Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis. Annals of the rheumatic diseases 2017;76:1150-8.
3. Richard N, Hudson M, Gyger G, Baron M, Sutton E, Khalidi N, Pope JE, Carrier N, Larche M, Albert A, Fortin PR, Thorne C, Masetto A. Clinical correlates of faecal incontinence in systemic sclerosis: identifying therapeutic avenues. Rheumatology (Oxford, England) 2017;56:581-8.
4. Nevskaya T, Baron M, Pope JE. Predictive value of European Scleroderma Group Activity Index in an early scleroderma cohort. Rheumatology (Oxford, England) 2017;56:1111-22.
5. Mejia Otero C, Assassi S, Hudson M, Mayes MD, Estrada YMR, Pedroza C, Mills TW, Walker J, Baron M, Stevens W, Proudman SM, Nikpour M, Mehra S, Wang M, Fritzler MJ. Antifibrillarin Antibodies Are Associated with Native North American Ethnicity and Poorer Survival in Systemic Sclerosis. The Journal of rheumatology 2017;44:799-805.
6. Li G, Adachi JD, Cheng J, Thabane L, Hudson M, Fritzler MJ, Lorenzi S, Baron M, Larche M. Relationship between calcium channel blockers and skin fibrosis in patients with systemic sclerosis. Clinical and experimental rheumatology 2017.
7. Levis B, Kwakkenbos L, Hudson M, Baron M, Thombs BD. The association of sociodemographic and objectively-assessed disease variables with fatigue in systemic sclerosis: an analysis of 785 Canadian Scleroderma Research Group Registry patients. Clinical rheumatology 2017;36:373-9.
8. Jewett LR, Kwakkenbos L, Hudson M, Baron M, Thombs BD. Assessment of English-French differential item functioning of the Satisfaction with Appearance Scale (SWAP) in systemic sclerosis. Body image 2017;22:97-102.
9. Hao Y, Hudson M, Baron M, Carreira P, Stevens W, Rabusa C, Tatibouet S, Carmona L, Joven BE, Huq M, Proudman S, Nikpour M. Early Mortality in a Multinational Systemic Sclerosis Inception Cohort. Arthritis & rheumatology (Hoboken, NJ) 2017;69:1067-77.
10. Baron M. Pros and cons of echocardiography in the screening, diagnosis and follow-up of patients with systemic sclerosis pulmonary arterial hypertension – a rheumatologist’s perspective. J scleroderma relatdisord 2017.
11. Wu M, Assassi S, Salazar GA, Pedroza C, Gorlova OY, Chen WV, Charles J, Taing ML, Liao K, Wigley FM, Hummers LK, Shah AA, Hinchcliff M, Khanna D, Schiopu E, Phillips K, Furst DE, Steen V, Baron M, Hudson M, Zhou X, Pope J, Jones N, Docherty P, Khalidi NA, Robinson D, Simms RW, Silver RM, Frech TM, Fessler BJ, Fritzler MJ, Molitor JA, Segal BM, Movahedian M, Martin J, Varga J, Mayes MD. Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients. Arthritis research & therapy 2016;18:20.
12. Leclair Valérie, MH, Susanna M. Proudman, Wendy M. Stevens, Marvin J. Fritzler, Mianbo Wang, Mandana Nikpour, Murray Baron Subsets in systemic sclerosis: one size does not fit all. J scleroderma relatdisord 2016;1:298 – 306
13. Valenzuela A, Baron M, Herrick AL, Proudman S, Stevens W, Rodriguez-Reyna TS, Vacca A, Medsger TA, Jr., Hinchcliff M, Hsu V, Wu JY, Fiorentino D, Chung L. Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: A Scleroderma Clinical Trials Consortium study. Seminars in arthritis and rheumatism 2016;46:344-9.
14. Levis B, Rice DB, Kwakkenbos L, Steele RJ, Hagedoorn M, Hudson M, Baron M, Thombs BD. Using Marital Status and Continuous Marital Satisfaction Ratings to Predict Depressive Symptoms in Married and Unmarried Women With Systemic Sclerosis: A Canadian Scleroderma Research Group Study. Arthritis care & research 2016;68:1143-9.
15. Khanna D, Berrocal VJ, Giannini EH, Seibold JR, Merkel PA, Mayes MD, Baron M, Clements PJ, Steen V, Assassi S, Schiopu E, Phillips K, Simms RW, Allanore Y, Denton CP, Distler O, Johnson SR, Matucci-Cerinic M, Pope JE, Proudman SM, Siegel J, Wong WK, Wells AU, Furst DE. The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis. Arthritis & rheumatology (Hoboken, NJ) 2016;68:299-311.
16. Jewett LR, Malcarne VL, Kwakkenbos L, Harcourt D, Rumsey N, Korner A, Steele RJ, Hudson M, Baron M, Haythornthwaite JA, Heinberg L, Wigley FM, Thombs BD. Development and Validation of the Body Concealment Scale for Scleroderma. Arthritis care & research 2016;68:1158-65.
17. Hudson M, Luck Y, Stephenson M, Choi MY, Wang M, Baron M, Fritzler MJ. Anti-HMGCR antibodies in systemic sclerosis. Medicine 2016;95:e5280.
18. Hoa S, Hudson M, Troyanov Y, Proudman S, Walker J, Stevens W, Nikpour M, Assassi S, Mayes MD, Wang M, Baron M, Fritzler MJ. Single-specificity anti-Ku antibodies in an international cohort of 2140 systemic sclerosis subjects: clinical associations. Medicine 2016;95:e4713.
19. Harel D, Hudson M, Iliescu A, Baron M, Steele R. Summed and Weighted Summary Scores for the Medsger Disease Severity Scale Compared with the Physician’s Global Assessment of Disease Severity in Systemic Sclerosis. The Journal of rheumatology 2016;43:1510-8.
20. Baron M, Pope J, Robinson D, Jones N, Khalidi N, Docherty P, Kaminska E, Masetto A, Sutton E, Mathieu JP, Ligier S, Grodzicky T, LeClercq S, Thorne C, Gyger G, Smith D, Fortin PR, Larche M, Abu-Hakima M, Rodriguez-Reyna TS, Cabral-Castaneda AR, Fritzler MJ, Wang M, Hudson M. Calcinosis is associated with digital ischaemiain systemic sclerosis-a longitudinal study. Rheumatology (Oxford, England) 2016;55:2148-55.
21. Baron M, Hudson M, Dagenais M, Macdonald D, Gyger G, El Sayegh T, Pope J, Fontaine A, Masetto A, Matthews D, Sutton E, Thie N, Jones N, Copete M, Kolbinson D, Markland J, Nogueira-Filho G, Robinson D, Fritzler M, Wang M, Gornitsky M. Relationship Between Disease Characteristics and Oral Radiologic Findings in Systemic Sclerosis: Results From a Canadian Oral Health Study. Arthritis care & research 2016;68:673-80.
22. Adina Coroiu LK, Brooke Levis, Marie Hudson, Murray Baron, David Cella, Brett D. Thombs The comparability of Functional Assessment of Chronic Illness Therapy – Fatigue scores between cancer and systemic sclerosis. Journal of scleroderma and related disorders 2017.
23. Greenfield J, Hudson M, Vinet E, Fortin PR, Bykerk V, Pineau CA, Wang M, Bernatsky S, Baron M. A comparison of health-related quality of life (HRQoL) across four systemic autoimmune rheumatic diseases (SARDs). PloS one 2017;12:e0189840.
24. Hudson M, Bernatsky S, Colmegna I, Lora M, Pastinen T, Klein Oros K, Greenwood CMT. Novel insights into systemic autoimmune rheumatic diseases using shared molecular signatures and an integrative analysis. Epigenetics 2017;12:433-40.
25. Lagares D, Ghassemi-Kakroodi P, Tremblay C, Santos A, Probst CK, Franklin A, Santos DM, Grasberger P, Ahluwalia N, Montesi SB, Shea BS, Black KE, Knipe R, Blati M, Baron M, Wu B, Fahmi H, Gandhi R, Pardo A, Selman M, Wu J, Pelletier JP, Martel-Pelletier J, Tager AM, Kapoor M. ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis. Nature medicine 2017;23:1405-15.
26. Lagares D, Santos A, Grasberger PE, Liu F, Probst CK, Rahimi RA, Sakai N, Kuehl T, Ryan J, Bhola P, Montero J, Kapoor M, Baron M, Varelas X, Tschumperlin DJ, Letai A, Tager AM. Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis. Science translational medicine 2017;9.