Urinary high-mobility group box-1 associates specifically with lupus nephritis class V

Abstract

Introduction High mobility group box 1 protein (HMGB-1) has been implicated in the pathogenesis of lupus nephritis (LN). There is increased HMGB-1 expression in the kidneys and increased levels are observed in serum and urine of patients with LN. This study was performed to determine whether the increased urinary HMGB-1 was specific for active lupus or secondary to renal damage. Methods Urine from 61 lupus patients (32 had active LN and 29 had SLE with no evidence of LN) and 14 control proteinuric patients (all with hypertension and 8 also with diabetes) were included in this study. HMGB-1 was detected by western blot. Urine protein was normalized to urine creatinine to account for volume of the specimen. Results Median normalized urine HMGB-1 levels were significantly elevated in LN patients compared to lupus patients without kidney disease (53.81 vs. 9.46, p<0.001). A difference in median levels was seen between LN classes; with a significant difference between proliferative and membranous disease (33.4 vs. 138.8, p=0.003). Urine protein to urine creatinine ratio (P/C) correlated with urinary HMGB-1 (r=0.52, p<0.001), but across the classes this was true only for membranous disease (r=0.71, p=0.022, proliferative, p=0.63; mixed, p=0.34). Conclusions HMGB-1 is elevated in the urine of patients with active LN. Levels are associated with LN class and higher levels of urinary HMGB-1 are seen in patients with class V when compared to both proliferative and mixed classes. Therefore, urinary HMGB-1 may be suggestive of membranous LN and warrants further evaluation in large lupus cohort and control disease.

HMGB1+ microparticles present in urine are hallmarks of nephritis in patients with systemic lupus erythematosus

“…provided important evidence implicating HMGB1 as a mediator of LN . A previous study showed that the levels of HMGB1 are elevated in the blood and urine of these patients; renal biopsies showed increased extranuclear HMGB1 expression predominantly outlining the glomerular endothelium and in the mesangium, and blood elevation of HMGB1 in patients with different histopathological forms of LN , and urinary HMGB1 in severe forms of LN . Our data are consistent with these reports because an important percentage of MP‐HMGB1 + were also CD14 + , and additionally indicate that MPs are an important source of HMGB1 in the urine of LN patients and that MP‐HMGB1 + frequency was increased in patients with active LN; however because these last values were overlapping between some patients, these vesicles seem not to be very suitable as biomarkers to differentiate between active and inactive renal involvement.…”

Association of anti-CLIC2 and anti-HMGB1 autoantibodies with higher disease activity in systemic lupus erythematosus patients

“…In our study anti-HMGB1 autoantibody levels were positively associated with higher SLEDAI score, a finding similar to that reported in earlier studies. [ 6 7 13 15 ] In our study anti-CLIC2 autoantibody levels were likewise associated with higher SLEDAI score, which is similar to the observations reported by Huang et al . [ 4 ]…”

“…[ 11 ] Previous studies have reported that anti-HMGB1 autoantibody levels correlated with the pathogenesis of kidney diseases in patients with lupus nephritis and vasculitis with renal involvement. [ 12 13 14 ] Majority of the SLE patients in our cohort did not experience active renal involvement (86%), and this might partially explain the lack of significant anti-HMGB1 autoantibody levels in our study. Nevertheless, anti-HMGB1 autoantibody levels were positively associated with a higher SLEDAI score in our cohort of SLE patients, suggesting that HMGB1 plays a role in disease activity and is involved in causing organ damage.…”

Persistent Bacteriuria and Antibodies Recognizing Curli/eDNA Complexes From Escherichia coli Are Linked to Flares in Systemic Lupus Erythematosus

“…After informed consent was obtained, blood and urine samples were collected from patients who fulfilled at least 4 of the Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE (14). Blood was processed as described previously (15). At each clinic visit, each TLC participant undergoes a physical examination and review of the complete medical history, including medications.…”