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Non‐invasive biomarkers for systemic lupus erythematosus: A lookback at 2016

Early diagnosis, accurate assessment of disease activity and monitoring of disease flares in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) remain huge challenges due to the lack of validated biomarkers with good sensitivity and specificity profiles. Conventional clinical parameters, such as antidouble stranded DNA (anti-dsDNA), complement C3 and proteinuria, are not sensitive enough for the early diagnosis and monitoring of disease activity, renal flares or long-term outcomes. In recent years, several promising biomarkers for the early diagnosis and monitoring of SLE and LN have been evaluated. Here, we take stock of the largest studies that have been reported over the past year, 2016. SLE is an autoimmune disease with multiple organ involvement, and diverse clinical manifestations. LN is one of the commonest and most ominous clinical manifestations of SLE and accounts for significant morbidity and mortality in SLE patients. Although improvements in 5and 10-year SLE/LN survival rates have been reported in recent years, early diagnosis and monitoring disease flares remain a big challenge. Traditional clinical and laboratory parameters, such as anti-dsDNA, C3, proteinuria, and estimated glomerular filtration rate (eGFR) are not sensitive for the early diagnosis and monitoring of treatment responses. A renal biopsy is the gold standard for the diagnosis and prognosis of LN, but it is invasive and not practical for routine monitoring of disease activity. An increasing number of studies focus on identifying non-invasive biomarkers for the early diagnosis and monitoring of SLE and LN. Three recent articles published in this journal focus on different aspects of SLE biology. Tozkir et al. have reported that the frequencies of classes I and II antihuman leukocyte antigen (HLA) antibodies were higher in SLE and scleroderma patients than in healthy controls. Interestingly, frequencies of thrombocytopenia, anti-ribonucleoprotein and anti-Ro antibodies were higher in the class I antibody-positive SLE group. In a second study, Banica et al. reported that SLE patient peripheral blood mononuclear cells (PBMCs) exhibited a cluster of anergy-related phenotypes, including reduced regulatory T cells (Tregs), Cbl-b and egr2 message, although association to disease activity or SLE manifestations were not examined. In a third article, Huang et al. reported that macrophages from SLE patients exhibited reduced phagocytic capacity compared to those from healthy controls. The SLE-associated phenotypes described in these three recent articles may also have potential biomarker applications, although the specificity and sensitivity of these phenotypes were not pursued in these studies. Regardless, when the literature beyond this journal was surveyed, the past year has witnessed a flurry of articles in the arena of SLE biomarkers. When we searched PubMed, Medline and Embase databases for original English-language articles published in 2016 using the following search terms (title or abstract), ‘systemic lupus erythematous’ OR ‘SLE’ OR ‘lupus nephritis’ OR ‘LN’ and ‘biomarkers’ OR ‘RNA’ OR ‘protein’ OR ‘metabolites’ that focused only on human studies, 31 articles satisfied these criteria. From these, 17 publications that had utilized the largest sample sizes (n ≥ 70) are summarized in Table 1. Highlights from these studies are summarized below.