August 30, 2012
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Protein might be marker for renal inflammation in patients with lupus

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The nuclear nonhistone protein high mobility group box 1 might indicate renal and systemic inflammation in patients with systemic lupus erythematosus, according to recent data.

Researchers investigated 69 patients (median age, 41 years; 60 women) with systemic lupus erythematosus (SLE), including 21 with biopsy-proven lupus nephritis (LN), 15 with an LN history but no current activity and 33 with nonrenal SLE. There also were 17 controls (median age, 26 years; 15 women). Clinical and serological parameters were assessed and Western blotting was used to measure serum and urine levels of high mobility group box 1 (HMGB1), which is secreted from various cells during activation and/or cell death. An analysis was performed on HMGB1 expression in renal biopsies of 17 patients with active LN.

Active LN patients had significantly higher serum (intensity, 57; 11-350) and urinary levels (intensity, 54; 4-300) of HMGB1 compared with patients without active LN (serum intensity, 16; 2-92; urine intensity, 4; 0-300) and controls (serum intensity, 6; 1-38; urine intensity, 0; 0-4). The cohort also had renal tissue showing strong expression of HMGB1 at cytoplasmic and extracellular sites, suggesting active release of HMGB1. Patients with SLE but not active LN displayed higher serum (intensity, 20; 2-80) and urinary levels than controls (intensity, 13; 2-92). SLE disease activity index (SLEDAI) correlated with urinary HMGB1 levels (r=0.54; P<.0001), which showed a negative correlation with complement factor 3 (r=–0.38; P=.008) in sera.

“The study demonstrates an increase in urine HMGB1 levels in SLE patients, in particular in those with active LN,” the researchers concluded. “Increase in urine MHGB1 levels correlated to [SLEDAI]. Accordingly, renal tissue of LN patients showed an increase in nuclear HMGB1 release compared to control tissue.

“We suggest that HMGB1 may play an important role in renal pathology in SLE patients.”