Urinary G3BP as a Novel Biomarker in Lupus Nephritis

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multisystem involvement. The condition has several phenotypes, with varying clinical presentations from mild mucocutaneous manifestations to multiorgan and severe central nervous system involvement. Several immunopathogenic pathways play a role in the development of SLE. Hargraves described the lupus erythematosus (LE cell) in 1948. Several pathogenic autoantibodies have since been identified. Despite recent advances in technology and understanding of the pathological basis and risk factors for SLE, the exact pathogenesis is still not well known. Diagnosis of SLE can be challenging, and while several classification criteria have been posed, their utility in the clinical setting is still a matter of debate. Management of SLE is dictated by organ system involvement. Despite several agents shown to be efficacious in treating SLE, the disease still poses significant morbidity and mortality risk in patients.

Lupus nephritis (LN) is a highly prevalent and serious clinical manifestation among patients with systemic lupus erythematosus (SLE). It affects up to 60% of patients, depending on the examined cohort. Although SLE management has improved, LN still represents a difficult to treat manifestation, with renal flares occurring in about half of the patients and development of end stage renal disease (ESRD) in 5%20% of patients.

Lupus nephritis directly contributes to SLE-related mortality, both in the early and later disease phase.

Lupus nephritis diagnosis relies on kidney biopsy, which is instrumental for histological characterization, and treatment decisions. However, the biopsy procedure is invasive, often associated with discomfort for the patient, and sometimes with bleeding complications. Although repeated biopsies have been shown to be of value, their utility still remains controversial for verifying treatment effects, monitoring disease and predicting outcomes in clinical practice.

In this context, it is highly desirable to identify new non-invasive biomarkers that may reflect the type of kidney involvement, reflect the degree of histological activity and damage, predict LN flares and be useful for assessing treatment response. In this respect, urinary biomarkers are of high relevance since they can serve as liquid biopsy and reveal pathogenic events taking place in the kidney.

the investigators investigated urinary Galectin-3 binding protein (u-Gal-3BP) as a novel candidate biomarker for disease activity in renal lupus, here studied in a real life SLE cohort.

Gal-3BP is an interferon-inducible secreted scavenger protein belonging to the lectin family. in SLE, previous studies have demonstrated high expression of Gal-3BP in blood, both in systemic and cutaneous forms of lupus, and the protein was found in circulating macrovesicles, as well as in macrovesicles in the context of immune deposits in the kidney.