Lupus: 3 New Things

Aug 06, 2018

Two recent studies underscore the key role of interferon in SLE; a third trial identifies a link between undiagnosed vertebral fractures and organ damage in women with lupus.

References1. Md Yusof MY, Psarras A, El-Sherbiny YM, et al. Prediction of autoimmune connective tissue disease in an at-risk cohort: prognostic value of a novel two-score system for interferon status. Ann Rheum Dis. Published online first: 21 June 2018. doi: 10.1136/annrheumdis-2018-213386.2. Kato Y, Park J, Takamatsu H, et al. Apoptosis-derived membrane vesicles drive the cGASâSTING pathway and enhance type I IFN production in systemic lupus erythematosus. Ann Rheum Dis. Published online first: 26 June 2018. doi: 10.1136/annrheumdis-2018-212988.3. Shkireeva S, Lesnyak O, Zotkin E. Influence of undiagnosed vertebral fractures on organ damage in women with systemic lupus erythematosus. Ann Rheum Dis. 2018;77:405. Abstract THU0377.

Type I interferon plays a key role in the development and progression of systemic lupus erythematosus (SLE). Two clinical studies underscore the importance of interferon in patients with SLE: a novel two-score system for interferon status can predict autoimmune connective tissue disease and a step-by-step account identifies a model of SLE pathophysiology.^1,2 A third study shows how undiagnosed vertebral fractures influence organ damage in women with SLE.³

Scroll through the slides for the latest findings and their clinical implications.

(Blood vials: ©Africa Studio/Shutterstock.com; genes: ©Lonely/Shutterstock.com; spine: ©Lightspring/Shutterstock.com.)

A combination of a two-factor interferon score plus family history can predict progression of autoimmune connective tissue disease in patients with lupus, which may lead to earlier intervention to prevent disease and avoid irreversible organ damage.

A prospective observational study included 118 patients who were at risk for progression to autoimmune connective tissue diseases. Blood and skin biopsy samples were analyzed for two interferon-stimulated gene expression scores previously used to identify clinically meaningful differences in those with autoimmune diseases. In addition, 49 healthy controls and 114 patients with SLE were used as negative and positive controls.¹

At 12-month follow-up, 19 of 118 patients (16%) progressed to at-risk status, including 14 patients with SLE and 5 patients with primary Sjogren disease. At baseline, both interferon scores differed among at-risk, healthy controls and SLE groups, and both were elevated in at-risk patients who progressed versus non-progressors.

Clinical implications: “Referrals of ANA-positive individuals to rheumatologists have increased over the last decade. Concerns are that these at-risk individuals may be discharged prematurely or be observed in an inefficient ‘watch and wait’ fashion until the diagnosis is clear, by which time the potential to prevent disease and confer the most benefit may be lost,” stated the researchers, led by Md Yuzaiful Md Yusof of the University of Leeds in the UK. “Our findings offer a novel approach, biomarkers, and have implications for future development of targeted therapies for this group of patients.”

A model of recurrent type I interferon production in patients with SLE provides crucial evidence of the pathophysiology of the disease.

Blood was collected from 64 patients with SLE, 31 patients with other autoimmune diseases, and 35 healthy controls, and then assayed using a cell-based reporter system that enables highly sensitive detection of interferon-I and interferon-stimulated gene (ISG)-inducing activity.²

The levels of interferon-I bioactivity and ISG-inducing activity were associated with SLE disease activity. Double-stranded DNA levels were elevated in SLE, and apoptosis-derived membrane vesicles from SLE-derived blood had high ISG-inducing activity.

Clinical implications: “We showed that SLE serum induced ISGs, in part, through a component of the innate immune system that functions to detect the presence of cytosolic DNA and, in response, trigger expression of inflammatory genes,” said lead author Yasuhiro Kato of Osaka University in Japan. The results suggest promise for targeting this pathway for SLE treatment. The cell-based reporter system may be useful for stratifying patients with SLE with high ISG-inducing activity.

Detection of vertebral fractures helps in assessing accumulated organ damage in women with SLE.

A study of 197 women with SLE sought to identify risk factors associated with critical organ damage. More than one-quarter (27.9%) of the patients developed vertebral fractures. Half of all women with SLE had asymptomatic vertebral fractures that were diagnosed for the first time. Two-thirds (66.5%) of the women with SLE had critical organ damage.³

The cumulative dose of glucocorticoids and previous therapy with cyclophosphamide were significantly associated with critical damage in women with SLE.

Clinical implications: “Vertebral fracture assessment in combination with dual energy X-ray absorptiometry in women with SLE is an effective method for diagnosis of asymptomatic vertebral fractures,” stated the researchers, led by S. Shkireeva of North-Western State Medical University in Saint-Petersburg, Russia.