B Original: B Cells, Non-Invasive Biomarkers & More

Dr. Pascual discussed these findings in a clinical context with respect to therapeutic trials in patients with SLE that, over the years, have often failed to meet primary end points. Many possible reasons exist for this failure (e.g., Outcome measures may not have captured clinically meaningful changes; high background immunosuppressive therapy may have masked the effects of the medication being studied.). She argued that one source of failure may be the molecular heterogeneity of SLE, as illustrated by her group’s work.

With the discovery of SLE granulocytes and erythroid cells as sources of interferon-genic mitochondrial nucleic acids, Dr. Pascual believes the rheumatology research community must incorporate the molecular stratification of patients with SLE into the design of future clinical trials. In doing so, researchers are more likely to see the appropriate grouping of patients and find the benefit of targeted therapies that take advantage of our understanding of disease pathogenesis at a minute level.

Lupus Nephritis

Dr. Fava

The final speaker in the session was Andrea Fava, MD, director of Lupus Translational Research, Johns Hopkins University School of Medicine, Baltimore. Dr. Fava began by reminding the audience of a few sobering facts about lupus nephritis:

• It occurs in up to half of patients with SLE;
• It is associated with significantly increased mortality compared with patients without lupus nephritis; and
• 10–30% of patients with lupus nephritis progress to renal failure and require dialysis.⁴

For these reasons, the Accelerating Medicines Partnership (AMP)—a collaborative effort between the U.S. National Institutes of Health, the U.S. Food & Drug Administration, multiple biopharmaceutical and life science companies, and nonprofit organizations seeking to transform the development of new diagnostics and treatments—considers lupus nephritis one of its key areas of interest. Dr. Fava’s work as part of AMP has been dedicated to urine proteomics, the large-scale analytical study of the proteins present in urine.

As Dr. Fava noted, urine routinely collects and contains byproducts of kidney inflammation in real-time. Thus, urine proteomics serves as a non-invasive method for discovering biomarkers that can be used to diagnose, monitor treatment response and understanding the pathophysiology of lupus nephritis.

Through this work, Dr. Fava and colleagues have found that urinary biomarkers of monocyte/neutrophil degranulation, macrophage activation, wound healing and matrix degradation, and interleukin (IL) 16 help characterize the aggressive proliferative forms of lupus nephritis and correlate well with histological activity on renal biopsies. Additionally, a decline in these biomarkers after three months of treatment can predict treatment response at one year better than measurements of proteinuria, the current gold standard in clinical practice.⁵