Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study.

INTRODUCTION: TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-kappaB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has been recently introduced. Thus, TWEAK levels may serve as an indication of LN presence and activity. METHODS: Multicenter cohorts of systemic lupus erythematosus (SLE) patients and controls were recruited for cross-sectional and longitudinal analysis of urinary TWEAK (uTWEAK) and/or serum TWEAK (sTWEAK) levels as potential biomarkers of LN. The performance of TWEAK as a biomarker for nephritis was compared with routinely used laboratory tests in lupus patients, including anti-double stranded DNA antibodies and levels of C3 and C4. RESULTS: uTWEAK levels were significantly higher in LN patients than in non-LN SLE patients and other disease control groups (P = 0.039). Furthermore, uTWEAK was better at distinguishing between LN and non-LN SLE patients than anti-DNA antibodies and complement levels, while high uTWEAK levels predicted LN in SLE patients with an odds ratio of 7.36 (95% confidence interval = 2.25 to 24.07; P = 0.001). uTWEAK levels peaked during LN flares, and were significantly higher during the flare than at 4 and 6 months prior to or following the flare event. A linear mixed-effects model showed a significant association between uTWEAK levels in SLE patients and their disease activity over time (P = 0.008). sTWEAK levels, however, were not found to correlate with the presence of LN or the degree of nephritis activity. CONCLUSIONS: High uTWEAK levels are indicative of LN, as opposed to non-LN SLE and other healthy and disease control populations, and reflect renal disease activity in longitudinal follow-up. Thus, our study further supports a role for TWEAK in the pathogenesis of LN, and provides strong evidence for uTWEAK as a candidate clinical biomarker for LN.

Relapsing polychondritis presenting with complete heart block.

Relapsing polychondritis (RP) is a rare autoimmune disease characterized by recurrent inflammation of cartilagenous structures, including the ears, nose, trachea, and joints. Cardiovascular involvement is relatively common, but involvement of the conduction system leading to various degrees of heart block is a rare and late manifestation of the disease usually requiring a pacemaker. We report here a patient with RP who presented with complete heart block that resolved promptly after treatment with prednisone. To our knowledge, this is the first reported case of RP with abnormal cardiac conduction on initial presentation and a rapid response to anti-inflammatory treatment. Heart block during the phase of active inflammation may respond to corticosteroid treatment as in our patient without the need for cardiac pacing.

Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis.

OBJECTIVE: Pathogenic monoclonal anti-double-stranded DNA (anti-dsDNA) antibodies up-regulate the expression of lipocalin-2 in glomerular mesangial cells. This study was undertaken to investigate whether polyclonal anti-dsDNA antibodies promote the local secretion of lipocalin-2 in the kidneys of patients with systemic lupus erythematosus (SLE), and whether urinary lipocalin-2 represents a marker of kidney involvement in SLE. METHODS: Hispanic, African American, and white patients with SLE and normal healthy control subjects from affiliated hospitals of the Albert Einstein College of Medicine were recruited for this cross-sectional study. Patients were classified based on the presence of active renal disease according to the SLE Disease Activity Index (SLEDAI). Correlations of clinical and laboratory data with urinary and serum levels of lipocalin-2 were assessed. RESULTS: Among SLE patients, urinary lipocalin-2 levels were significantly higher in those with lupus nephritis (LN) (median 17.1 ng/mg creatinine, interquartile range [IQR] 10.3-45.4; n = 32) than in those without LN (median 11.2 ng/mg creatinine, IQR 3.1-20.3; n = 38) (P = 0.023). Compared with the values in normal controls (median 4 ng/ml, IQR 0-11.1; n = 14), urinary levels of lipocalin-2 in SLE patients were significantly higher (non-normalized median 19.3 ng/ml, IQR 8-34.2) (P = 0.004). The presence of lipocalin-2 in the urine of patients with LN correlated significantly with the renal SLEDAI score (r = 0.452, P = 0.009), but not with extrarenal disease activity. CONCLUSION: The high prevalence of LN in SLE patients and the prognostic significance of kidney disease support the need for identifying early biomarkers to assess the risk of nephritis development and for following up patients with established disease. These findings indicate that urinary lipocalin-2 is a potential marker of the presence and severity of renal involvement in adult patients with SLE.

Trigeminal neuralgia as the first manifestation of mixed connective tissue disorder.

This report describes a patient with mixed connective tissue disease (MCTD) and trigeminal neuralgia (TN). Features of her TN, along with those of the 6 previously reported patients with TN and MCTD such as bilaterality and response to steroid therapy, suggest that the TN in MCTD differs from the idiopathic form of the disease. Because the TN often precedes other features of the MCTD, it may be useful to test patients with atypical TN for the presence of anti-RNP antibodies in order to identify a subset with both systemic disease and a potential to respond to corticosteroid therapy.