To assess the relationship between serum C3 or C4 levels and lupus renal flare, C3 and C4 levels were measured bimonthly in 71 lupus nephritis patients for a mean of 35 months, during which time 70 renal flares were identified. Comparing baseline, pre-flare, and at-flare values indicated that neither C3 nor C4 levels decreased pre-flare, but both decreased on average significantly at flare. However, sensitivity/specificity for C3 (75%/71%) and C4 (48%/71%) were low. To account for other influencing factors, multiple regression was performed that included bimonthly values of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and genotype data on C3 (S/F), CRP (1846G > A), and the complement regulator factor H (Y402H). This analysis revealed that reduced levels of C4, but not C3, were independently associated with the two-month pre-flare period. Conversely, reduced levels of C3, but not C4, were independently associated with the flare visit. Significant pro-flare interactions included low C3 levels with the factor H 402HH-encoding genotype, and low CRP levels with the C3 F allele. Together these data suggest that C4 activation is critical for initiating renal flare while C3 activation is involved in the actual tissue damage, and that these effects are influenced by genetic variability in complement activation and regulation.

25-hydroxyvitamin D3 correlated inversely and significantly with clinical SLE activity, anti-C1q and anti-dsDNA titers, but not with complement levels or damage scores. Deficiency of 25-hydroxyvitamin D3 was as specific as anti-C1q, but less sensitive than anti-dsDNA, for detecting concurrent renal and non-renal clinical activity of SLE.

Cross-sectional studies have shown that low vitamin D (25-hydroxyvitamin D (25(OH)D)) is associated with increased systemic lupus erythematosus (SLE) activity. This study is the first to assess the temporal relationship between 25(OH)D levels and onset of SLE flare. This assessment was made possible because of the specimen bank and database of the Ohio SLE Study (OSS), a longitudinal study of frequently relapsing SLE that involved regular bimonthly patient follow-up. We identified for this study 82 flares from 46 patients that were separated by at least 8 months from previous flares. Serum 25(OH)D levels were measured at 4 and 2 months before flare, and at the time of flare (a flare interval). We found that for flares occurring during low daylight months (LDM, Oct-Mar), 25(OH)D levels were decreased at the time of flare, but only in non-African American (non-AA) patients (32% decrease at flare, compared to 4 months prior, p < 0.001). To control for seasonal effects, we also measured 25(OH)D levels in the LDM “no-flare” intervals, which were intervals that matched to the same calendar months of the patients’ LDM flare intervals, but that didn’t end in flare (n = 24). For these matches, a significant decrease occurred in 25(OH)D levels during the flare intervals (18.1% decrease, p < 0.001), but not during the matching no-flare intervals (6.2% decrease, p = 0.411). For flares occurring during high daylight months (HDM), 25(OH)D levels changed only in non-AA patients, increasing slightly (5.6%, p = 0.010). Analysis of flare rates for the entire OSS cohort (n = 201 flares) revealed a tendency for higher flare rates during LDM compared to HDM, but again only in non-AA patients (p = 0.060). Flare rates were lower during HDM for non-AA patients compared to AA patients (p = 0.028). In conclusion, in non-AA SLE patients, unusually large declines in 25(OH)D during LDM may be mechanistically related to SLE flare, whereas relatively high 25(OH)D levels during HDM may protect against flare.

Objectives:To study the effect of renal disease on standardized mortality ratio (SMR) and life expectancy (LE) of patients with systemic lupus erythematosus (SLE). Methods: Patients who fulfilled ³4 ACR criteria for SLE who were prospectively followed in our unit from 1995 to 2011 were studied. The cumulative survival rate (by Kaplan Meier's method), and age and sex adjusted standardized mortality ratio (SMR) was calculated. Life expectancy (LE) was studied by single decrement life table analysis. The effect of renal involvement, histological classes, renal damage and end stage renal disease (ESRD) on these parameters was evaluated. Results: 694 patients were studied (92%). The mean age of onset of SLE was 32.9±13.4 years (range 6-78). 368 (53%) had evidence of renal disease according to the ACR definition of renal involvement (persistent proteinuria of >0.5g/day; cellular casts or histological evidence). 285 (77%) patients had undergone renal biopsy for at least once. The distribution of histological classes (ISN/RPS) was as follows: class I (1%), class II (6%), class III (19%), class III+V (10%), class IV (47%), class V (16%) and others (1%). At the time of analysis, the mean observation of our patients since SLEonset was 9.6±7.3 years. Thirty-four (4.9%) patients were lost to follow-up. Among patients with lupus renal disease, 79 (11%) patients had renal damage as assessed by the SLE damage index (SDI) and 24 (3%) patients developed ESRD. The cumulative 5, 10 and 15 year survival of patients with renal involvement was 92.3%, 88.8% and 84.3%, respectively, which was significantly lower than that of patients without renal involvement (97.0%, 93.7% and 91.6%, respectively; p=0.004). Cox regression demonstrated that the age and sex adjusted hazard ratio (HR) of mortality in patients with renal disease and renal damage compared with those without renal involvement was 2.23 [1.29-3.85] (p=0.004) and 3.59 [2.20-5.87] (p<0.001), respectively ( Table 1). The corresponding hazard ratio for mortality in patients who developed ESRD was 9.20 [4.92-17.2] (p<0.001). Patients with proliferative types of lupus nephritis (class III, IV and III/IV+V) had significantly increased mortality compared to those without renal disease ]; p=0.01). In contrast, pure membranous lupus nephropathy was not associated with increased mortality (adjusted HR 1.09 [0.38-3.14]; p=0.88). Adjustment for the use of immunosuppressive regimens in the Cox regression models did not materially affect the overall hazard ratios for mortality. The age and sex adjusted SMRs of all SLE patients, SLE patients without renal disease, SLE patients with renal disease, proliferative nephritis, pure membranous nephropathy, renal damage and renal failure compared to the general population were 7.3 (95% confidence interval [CI] 5.

Objectives Hepcidin is an acute phase reactant produced by hepatocytes that has been linked to chronic inflammation and atherosclerosis. The present study was carried out to evaluate the serum hepcidin level in patients with SLE and its relationship with disease activity, organ damage and coronary atherosclerosis. Methods Consecutive patients who fulfilled ≥4 ACR criteria for SLE were recruited. Blood was taken from the participants at 9am in the morning for the assay of hepcidin (peptide enzyme immunoassay; Peninsula Lab, San Carlos, USA), complements (immunonephelometry; Siemens, Germany), anti-dsDNA titer (ELISA; Euro-diagnostica, Arnhem, Netherlands). SLE disease activity was assessed by the SELENA-SLEDAI and physician’s global assessment (PGA) scores. Organ damage of SLE was assessed by the ACR/SLICC damage index (SDI). Atherosclerosis of the coronary arteries was studied by a Multi-Detector CT (MDCT) scanner (BrillianceTM 16, Philips Medical Systems, Best, the Netherlands). The total calcium score (Agatston score) of left main, left anterior descending, left circumflex, and right coronary arteries was obtained and summated. An Agatston score of ≥1 was considered to be abnormal. Hepcidin level was correlated with SLEDAI score (Pearson’s correlation) and compared between patients with and without coronary calcification (Mann Whitney rank sum test). Results 290 SLE patients were recruited but interim data on 189 patients were analyzed. There were 178 (94%) women and 11 men. The mean age at SLE onset was 32.5±13 years and the mean disease duration was 8.6±7.2 years. At the time of venepuncture, the mean SLEDAI score was 3.3±2.9 (median 2.5) and the mean PGA score was 0.55±2.9 (median 0.4). Forty-three (23%) patients had active SLE, defined as a SLEDAI score of 5 points or more. The mean serum hepcidin level was 21.6±32.5 ng/ml (median 12.7; IQR 4.4-25.8). Serum hepcidin level did not correlate with the total SLEDAI score (r=0.08, p=0.30) or PGA score (r=0.13; p=0.07), but with clinical SLEDAI score, defined as total SLEDAI score minus those contributed by active lupus serology (anti-dsDNA elevation and complement depression) (r=0.18; p=0.02). Serum hepcidin level did not correlate with anti-dsDNA titer or complement levels. Among these 189 SLE patients, 97 patients were randomly screened for coronary atherosclerosis by MDCT scan. Twenty-four patients (25%) had abnormal Agatston calcium score (≥1 point) and the mean score of these patients was 52.0±69 (median 20; IQR 3-78). The serum hepcidin level was significantly higher in those with abnormal coronary calcium score than those without (38.6±54 vs 19.6±26.3 ng/ml; p=0.048) after adjustment for age and sex. Finally, serum hepcidin level was positively correlated with the SDI score (r=0.19; p=0.009). Conclusions In this cross-sectional study, serum hepcidin level correlates significantly with clinical SLE disease activity and damage score, but not with anti-dsDNA or complement level. SLE patients with coronary atherosclerosis have significantly higher hepcidin ...