High mobility group box protein 1 (HMGB1) serum and urinary levels and gene polymorphism in Egyptian patients with systemic lupus erythematosus: A possible relation to lupus nephritis

Abstract

Objective The aim of this study was to evaluate the effects of the high mobility group box protein 1 (HMGB1) serum and urinary levels and gene polymorphisms on systemic lupus erythematosus (SLE) development and investigate their link to lupus nephritis (LN). Methods We enrolled 120 Egyptian SLE patients and 120 healthy controls. Thorough medical and clinical evaluation were carried out, and SLE disease activity index (SLEDAI) was assessed. Lupus patients were divided into two groups according to the presence of LN. Measurement of HMGB1 serum and urinary levels was done using ELISA and genotyping for HMGB1 ( rs1045411) was performed. Results There were statistically significantly higher HMGB1 serum and urinary levels in SLE patients ( p < 0.001). There was a marginally significant association between lupus and alleles ( p = 0.059, φ = −0.086). ‘C’ allele was marginally significant risk allele for SLE. After classifying SLE patients based on the presence or absence of LN, there was no significant difference as regard sex ( p = 0.387), age ( p = 0.208) and disease duration ( p = 0.094).However, there was a significant difference between the 2 groups in regard to the frequency of musculoskeletal manifestations ( p = 0.035), SLEDAI score ( p < 0.001), both serum ( p < 0.001) and urinary HMGB1 levels ( p < 0.001) in addition to the frequency of HMGB1 genotypes ( p = 0.003). Lupus patients with C/T-T/T HMGB1 genotypes had 3.5-times higher odds to exhibit LN. Conclusions Serum and urine HMGB1 measurements are helpful in the diagnosis of SLE and the prediction of LN. There is a link between HMGB1 gene variations and the risk of SLE, with evidence that the C/T-T/T HMGB1 genotype is linked to a significantly greater risk of LN in the Egyptian population.

A Preliminary Predictive Model for Proliferative Lupus Nephritis in Juvenile Systemic Lupus Erythematosus

“…However, these biomarkers are imprecise and lack a robust model to differentiate between proliferative and non-proliferative renal lesions [23,39,40]. Recent research has also identified other promising serum and urinary biomarkers such as NGAL (neutrophil gelatinase-associated lipocalin), MCP-1 (monocyte chemoattractant protein), TWEAK (tumor necrosis factor-like weak inducer of apoptosis), VCAM (vascular cell adhesion molecule), adiponectin, hemopexin, kidney injury molecule-1 and HMGB1 (high mobility group box protein 1) [23,41]. However, these biomarkers are still experimental, and any future potential use will likely be hindered by the cost of these tests as well as the lack of availability, especially in low-resource countries.…”