Lupus nephritis affects up to 60% of patients with systemic lupus erythematosus. Current biomarkers are not reliable, but a novel “omic”-driven approach might be a more successful way for risk prediction.
“In lupus nephritis, we believe that ‘time is kidney’,” said Prof. Chaim Putterman (Albert Einstein College of Medicine, USA) . Lupus nephritis (LN) is a major risk factor for morbidity and mortality in systemic lupus erythematosus (SLE). According to a study, delay between the detection of the onset of renal disease and renal biopsy was a significant predictor for subsequent renal insufficiency and death due to lupus renal involvement. Therefore, biomarkers are of particular importance in LN, because early diagnosis and treatment make a difference. Prompt therapy with prednisone and immunosuppressive agents in LN has a beneficial effect on long-term prognosis.
Unfortunately, increasing double-stranded (ds)DNA antibodies, presently used as biomarkers, were predictive of flares in some, but not all, studies. Therefore, more reliable flare predictors are urgently needed. There is a need for better biomarkers for differentiating lupus versus other diseases, measuring disease activity, predicting outcomes/response to therapy, allowing assessment of response to therapy, and predicting long-term prognosis.
Promising agents are cell-bound complement activation products (CB-CAPs). Studies have shown that CB-CAPs can be helpful in the diagnosis of lupus and are more reliable than anti-dsDNA. Abnormalities in CB-CAPs are associated with higher disease severity in lupus patients.
“Terminal complement activation has also been assessed as a possible biomarker in LN. Tubular C9-positive staining was observed in 23% of biopsies of patients with LN and those patients had significantly higher proteinuria, interstitial fibrosis, and chronicity indices,” Prof. Putterman explained.
Big data are the new kid on the block, namely “omics”-driven research instead of hypothesis-driven research. In this approach, instead of a single marker, rather all molecules are assessed, so in more breadth than depth. “Instead of focusing on an individual molecule, we are profiling many analytes simultaneously. If you look at 5, 6, or 7 markers at a time, those perform much better than just a single mediator,” Prof. Putterman stated. In one study, 1,000 proteins in the urine of SLE patients were assessed using a quantitative planar protein microarray. In this study, the proteins angptl4, L-selectin, and TGF-β1 were associated with disease activity and were best at tracking concurrent or pending disease flares.
Concerning LN, urine proteins that best distinguish active LN from inactive disease are ALCAM, VCAM-1, Hemopexin, and TFP-1. The CD6-ALCAM pathway is an important driver of inflammation in LN and may also be an interesting target for drug development. Itolizumab is the first antibody that binds to CD6 and decreases pro-inflammatory cytokine secretion. It is now entering a phase-1 trial.
However, anti-dsDNA antibodies and complement components are still the best markers for early diagnosis of LN available today. “My prediction is that the goals of precision medicine in SLE will be realised through big data approaches, rather than tests on single mediators,” Prof. Putterman concluded.
- Putterman C. New biomarkers in lupus nephritis. 4S060, ACR Convergence 2020, 5-9 Nov.
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Table of Contents: ACR 2020
Letter from the Editor
ACR 2020 Highlights Podcast
Gout treatment with febuxostat: no higher cardiovascular mortality
New agent with great potential for the treatment of giant cell arteritis in the pipeline
Autotaxin inhibitor successful in the first trial in diffuse cutaneous systemic sclerosis
JAK inhibition as a treatment option for ankylosing spondylitis
Spotlight on Rheumatoid Arthritis
Persuasive long-term results for JAK inhibition in rheumatoid arthritis
Rheumatoid arthritis: new EULAR treatment guidelines
Rheumatoid arthritis and interstitial lung disease: a deadly combination
COVID-19 – What Rheumatologists Need to Know
COVID-19 in patients with rheumatic disease: most report mild disease
Poor disease control: a risk factor for severe COVID-19
No heightened outcome risk for rheumatic patients with COVID-19
What Is Hot in Lupus Nephritis?
Lupus nephritis biomarkers: moving toward an omic-driven approach
Lupus nephritis: new therapies on the horizon in 2020
Spondyloarthritis – The Beat Goes On
Artificial intelligence can help in the diagnosis of axSPA
Resolution of dactylitis or enthesitis is associated with improvements in joint and skin symptoms
Promising novel treatment option for psoriatic arthritis
How to Diagnose Large Vessel Vasculitis: Promises and Pitfalls
How to choose imaging modalities in large vessel vasculitis
Diagnosis of large vessel vasculitis with imaging
Osteoarthritis – Novel Developments
Knee osteoarthritis patients with indicators of inflammation could profit from methotrexate
Anticoagulation with vitamin K antagonist is associated with risk of knee and hip replacement
Osteoporosis – New Data
Bisphosphonate use: Asian American women have a smaller treatment benefit
Inflammatory disease as a risk factor for fractures
Best of the Posters
No progression of osteoarthritis with corticosteroid injections
Hydroxychloroquine use: no indication for arrhythmias in RA and SLE patients
Children with rheumatic disease have no greater risk of a COVID-19 infection
Insufficient antimalarial supply for rheumatic disease treatment in the early COVID-19 pandemic
Treatment decisions should not be guided by ultrasound findings
Immune-mediated diseases tied to risk of cancer