Novel Biomarkers for Lupus Nephritis in the “OMICS” Era

Abstract

: Lupus nephritis (LN) is a severe renal comorbidity associated with systemic lupus erythematosus (SLE), a complex autoimmune disorder with high morbidity and mortality. Diagnosis and monitoring of LN patients still rely on renal biopsy, a procedure that exposes patients to a variety of risks and is not capable of providing longitudinally information about disease prognosis. In this review, we summarized current data of recent promising biomarkers developed in the precision medicine era, particularly under genomic, transcriptomic, proteomic and metabolomic techniques. Genome-wide association-studies have been evaluating the role of endogenous elements beyond the autoimmunity in LN. Transcriptomic methods, including single-cell sequencing, are potential tools in identifying inflammatory signatures, miRNAs and gene expression. Proteomic measures, including anti-C1q antibodies, cytokines, TLRs, VCAM-1, NGAL osteopontin, angiostatin, have been considered helpful to provide a more profound comprehension of the disease pathogenic processes. Metabolomic approaches may identify several abnormal metabolites profiles related with the impairment of cellular functions. Together, these accurate, non-invasive and moderate-cost propedeutic resources may be the novel tools for recognizing, distinguishing and predicting LN progression and prognosis. Furthermore, omics evaluation may also predict responsiveness to treatment and, consequently, change the way we manage LN cases in the near future.

Urine Soluble CD163 Is a Promising Biomarker for the Diagnosis and Evaluation of Lupus Nephritis

“…The identification of non-invasive biomarkers, such as usCD163, of active LN that are strongly correlated with renal biopsy results and underlying disease mechanisms has been a priority. Other non-invasive biomarkers of LN include anti-C1q antibody and urine MCP-1 ( 18 , 31 ). The treatment goal should be an at least 25% and 50% reduction in the proteinuria level after 3 and 6 months, respectively, and a complete renal response (500–700 mg/day) at 12 months ( 32 ).…”

Aberrant expression of C1q, IL-6 and β-catenin in class VI lupus nephritis

“…Despite improvements in diagnosis and treatment in SLE patients with LN have been made, LN is still a serious risk factor for the development of ESRD and early mortality and disability in SLE [31] . Recent proteomic measures, including anti-C1q antibodies, cytokines, toll-like receptors (TLRs), vascular cellular adhesion molecule-1 (VCAM-1), neutrophil gelatinase-associated lipocalin (NGAL), angiostatin, have been considered helpful to provide a more profound comprehension of SLE pathogenic process [32] . Concerning cytokines, baseline serum and urine IL-6 can be used as a sensitive biomarker for SLE activity, as well as predictors of remission of LN [33] .…”

Potential Small Molecules for Therapy of Lupus Nephritis Based on Genetic Effect and Immune Infiltration

“…Currently, drug selection is primarily based on three principles: immunosuppression, immunomodulation, and symptomatic treatment [ 11 ]. Meanwhile, more studies are identifying genes that are implicated in the development and progression of LN [ 12 ], and researchers have sequenced kidney tissue from LN and documented them in the GEO database. Drug-gene relationships are continuously being enriched by further research and exploration.…”