High-titer antichromatin antibody is associated with proliferative class IV of lupus nephritis

The antichromatin antibody (aCT) has been described as a useful marker for lupus nephropathy. The relevance of its nephritogenic potential may be appropriately evaluated in the context of renal histopathology. Therefore, the present study investigated the relationship of aCT with a particular histopathologic class of lupus nephritis (LN). Seventy-eight consecutive patients with systemic lupus erythematosus (ACR criteria) and active nephritis who underwent renal biopsy from 1999 to 2004 and with available frozen serum sample obtained at the time of biopsy were selected. aCT was measured by ELISA, and anti-dsDNA was measured by indirect immunofluorescence (IIF) and by ELISA. All renal biopsies were revised in a blinded manner by the same expert renal pathologist. Charts were extensively reviewed for demographic and renal features obtained at the time of biopsy. The prevalence of aCT (≥20 U) was 59% with a mean titer of 74.3 ± 38.7U. Both aCT-positive and aCT-negative groups of patients had similar age, gender distribution, duration of lupus, and duration of renal disease. Anti-dsDNA was detected by IIF in 29.5% and by ELISA in 42.3% of the patients. Concomitant presence of both antibodies was observed in 63% (29/46) [anti-dsDNA by ELISA] and 45.6% (21/46) [anti-dsDNA by IIF] of the patients. Lower serum levels of C3 (73% vs. 40%, P  = 0.0058) and C4 (82% vs. 46.7%, P  = 0.0021) were more commonly observed in aCT ≥ 20 U patients compared to the aCT-negative group. It is important to note that the use of a higher cut-off value (≥40 U) for aCT test revealed a predominance of class IV LN (58% vs. 33%, P  = 0.039) in aCT ≥ 40 U compared to aCT < 40 U group. The mean levels of proteinuria, serum albumin, and creatinine were markedly altered but were comparable in both groups (P ≥ 0.05). One fourth (26.3%) of the 19 patients with class IV LN and aCT ≥ 40 U had no detectable anti-dsDNA (ELISA). These data suggest that high-titer aCT seems to be a valuable biomarker for proliferative class IV of LN.     

Renal arterial resistive index as a noninvasive biomarker of disease activity in lupus nephritis patients

Aim of the workTo evaluate the renal resistive index (RI) in lupus nephritis (LN) patients and to study its association with clinical features, laboratory investigations and LN pathological classes in systemic lupus erythematosus (SLE) patients.Patients and methodsThe study included 45 SLE patients and 25 matched controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into LN (renal SLEDAI ≥ 4) and no-renal activity (NRA) (renal SLEDAI = 0). Ultrasound Doppler renal examination was done to measure RI. Renal biopsies were performed in 30 LN patients.ResultsThe mean age of patients was 29.8 ± 10.1 years and disease duration 4.3 ± 3.9 years. They were 40 females and 5 males (F:M 8:1). Their SLEDAI was 10.9 ± 8.2 and renal SLEDAI was 5.2 ± 5.1. They were 30 with LN and 15 NRA SLE patients. Renal RI was significantly higher in LN patients compared to NRA SLE patients and controls (0.61 ± 0.04 vs. 0.55 ± 0.01 vs. 0.55 ± 0.02; p < 0.0001). RI significantly correlated with anti-double stranded deoxyribonucleic acid (anti-dsDNA) positivity (r = 0.33, p = 0.03), 24-hour proteins in urine (r = 0.38, p = 0.01) and negatively with creatinine clearance (r = -0.33, p = 0.03). Renal RI significantly correlated with pathological classes of renal biopsy (r = 0.65, p < 0.0001). At renal RI cut-off value 0.57 renal RI can detect renal activity with sensitivity of 83.3%, specificity of 82.5%, p < 0.0001. Renal RI ≥ 0.57 had higher activity index score compared to those with normal RI (5.7 ± 0.6 vs. 9 ± 3.3, p = 0.04). Conclusion: Renal RI was significantly increased in LN compared to NRA patients and was associated with laboratory parameters and pathological classes.     

Anti-nucleosome antibodies: A potential surrogate marker for renal affection in lupus patients with insignificant proteinuria

BackgroundLupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE). Clinical renal involvement is present in about two-thirds of lupus patients and more patients would have morphologic evidence of renal disease without clinical manifestations.Aim of the workTo investigate serum anti-nucleosome antibodies role as a biomarker for renal affection in lupus patients with insignificant proteinuria.Patients and methodsTwenty-four lupus patients with proteinuria <500 mg/d (group-A), 30 patients with established lupus nephritis (group-B) and 15 controls were included. Systemic lupus erythematosis disease activity index (SLEDAI), anti-nucleosome, anti-dsDNA antibodies and renal biopsy were assessed in all patients.ResultsSerum anti-nucleosome antibodies were significantly higher in all lupus patients than control (P < 0.001) and showed significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibody had more active disease by SLEDAI and higher levels of anti-nucleosome antibodies than those with negative anti-dsDNA antibodies. In both studied groups, serum anti-nucleosome antibodies were significantly higher in patients with class II LN than the control and in class III LN than in class II LN (P < 0.001). Yet, in both groups, anti-nucleosome was not useful in differentiating active from chronic renal affection.ConclusionSerum levels of anti-nucleosome antibodies are associated with active lupus disease and correlate with the degree of renal affection. In patients with insignificant proteinuria, serum levels of anti-nucleosome antibodies were elevated and were related to the degree of renal affection. Anti-nucleosome antibodies may be used as a surrogate marker for early renal affection in lupus patients with insignificant proteinuria.     

Serum level of CXCL 12 in patients with systemic lupus erythematosus: Is it worthy for predilection of lupus nephritis?

Aim of the workTo assess serum level of CXCL12 in systemic lupus erythematosus (SLE) patients and to study its relation to clinical features, disease activity and damage.Patients and methodsForty SLE patients and 40 controls were included. SLE disease activity index (SLEDAI) and the damage index were assessed. Serum CXCL12 level was measured using ELISA and renal biopsy done.ResultsThe mean age of the patients was 34.5 ± 10.4 years, disease duration 5 ± 5.2 years and were 38 females and 2 males (F:M 19:1). Renal biopsy was performed in 16 patients; 6 had inactive and10 active lupus nephritis (LN); 24 without signs suggestive of LN. Serum level of CXCL12 was significantly higher in patients (30.8 ± 16.9 ng/ml) than controls (20.2 ± 15.3 ng/ml) (p = 0.004). CXCL12 in patients with active LN (53.2 ± 25.3 ng/ml) was significantly elevated than those without LN (27 ± 12.5 ng/ml)(p < 0.001); and tended to be higher than those with inactive LN (34.2 ± 8.3 ng/ml)(p = 0.31). Levels were comparable between those with inactive LN and those without LN (p = 0.34). A significant correlation was found between serum CXCL12 and each of platelet count (p = 0.02), ANA titer (p = 0.007) and serum creatinine (p = 0.014). No significant correlations was found between CXCL12 and either SLEDAI (p = 0.59) or the damage index (p = 0.48). Alopecia was inversely associated with CXCL12 (p = 0.02).ConclusionCXCL12 is a potential key-player for SLE development. Adding this test to ANA, serum creatinine, platelet count and renal biopsy findings may enhance their diagnostic capacity for lupus nephritis and can help in early management and prediction of its prognosis.     

Anti-C1q antibodies are associated with systemic lupus erythematosus disease activity and lupus nephritis in northeast of China

This study aimed to investigate the associations of anti-C1q antibodies with systemic lupus erythematosus (SLE) disease activity and lupus nephritis (LN) in northeast of China. Ninety patients with SLE, 37 patients with other autoimmune diseases, and 40 healthy donors in northeast of China were enrolled. Serum anti-C1q antibodies were measured by ELISA with 20 RU/ml as the threshold of positive results. The prevalence and levels of anti-C1q antibodies in SLE group (50%, 20.54 ± 34.67 RU/ml) were significantly higher than those in autoimmune disease and healthy control groups (P < 0.05), yet no significant difference between LN patients and non-LN lupus patients (57.14% vs 41.46%, P > 0.05; 25.92 ± 39.94 vs 13.07 ± 27.39 RU/ml, P > 0.05). Anti-C1q antibody levels were positively correlated with levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-dsDNA, and anti-cardiolipin and negatively correlated with serum C3 and C4 (P < 0.05). The prevalence of anti-Sm and anti-nucleosome increased in anti-C1q-positive lupus patients (P < 0.05). Compared with anti-C1q-negative lupus patients, patients with 20–40 RU/ml anti-C1q antibodies had comparable disease activity (P > 0.05); patients with 40–80 RU/ml anti-C1q antibodies had significantly lower levels of serum complement (P < 0.05); patients with above 80 RU/ml anti-C1q antibodies had much more severe hypocomplementemia, increased SLEDAI scores, and higher incidence of hematuria and proteinuria (P < 0.05). Furthermore, the specificity and positive predictive value of 80 RU/ml anti-C1q antibodies for LN was 97.56% and 87.50%, respectively. In conclusion, anti-C1q antibodies are associated with SLE and LN disease activity, and the contribution hinges on the titers. Moreover, high-level anti-C1q antibodies are valuable for diagnosing LN.     

Association of serum uric acid with lupus nephritis in systemic lupus erythematosus

The aim of the present study is to assess the association of elevated serum uric acid (UA) with lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients. A total of 130 SLE patients were recruited, of whom 73 patients developed LN. Blood samples were obtained for determination of uric acid, complement 3 (C3), C-reactive protein (CRP) and some autoantibodies including anti-double-stranded DNA, -Smith, -SSA, -SSB, -U1RNP, SCL-70, and -Jo-1 antibodies. Correlations of UA with LN were assessed. UA was an independent risk factor for LN [odds ratio (95% CI): 1.01 (1.005–1.014); P = 0.0000]. The best cut-off value for UA using the ROC curve was 330 μmol/L (sensitivity 78.1% and specificity 75.4%) and the area under the ROC curve was 0.803 ± 0.039 (95% CI: 0.727–0.878, P = 0.000). Spearman’s correlation coefficient analysis showed negative association of UA with C3 in SLE patients with LN (r = −0.356, P = 0.002), but no association in those without LN. No correlations were found between UA and age, SLEDAI, CRP, IgG, IgM or IgA. Furthermore, analysis of covariance demonstrated that anti-Sm (β = −0.218, P = 0.004) and -U1RNP (β = 0.177, P = 0.008) autoantibodies were independent determinants of serum UA. The UA level is independently associated with the development of LN in SLE patients.     

Late onset lupus nephritis: analysis of clinical manifestations and renal pathological features in Chinese patients

The objectives of the study are to analyze the clinical and pathological features of 35 Chinese patients with late onset lupus nephritis (LN) in a single center. All the LN patients followed-up in our lupus clinic center from 1986 to 2008 were enrolled in this retrospective study. Thirty-five patients with a disease onset beyond the age of 50 years were identified. One hundred systemic lupus erythematosus (SLE) patients who had their disease onset before the age of 50 years were randomly recruited as controls. All of them received renal biopsy. The histological classifications were categorized according to 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. All of patients were Han Chinese. The mean age of onset of SLE for late onset and the control groups were 55.7 ± 6.5 years (range: 50–76) and 28.9 ± 7.6 years (range:18–48).The female to male ratio was smaller in the late onset SLE group, 2.9–1, compared with 7.3–1 in the control. The patients with hypertension in late onset LN were much more than that in control group. The renal histological classes showed no significant difference between the two groups. Classes IV, V, IV + V were common in late onset LN patients. There were no significant differences in extra renal manifestations except for a lower prevalence of malar rash, a higher leukopenia and skin vasculitis in the late onset patients. As to the immunological features, serum antineutrophil cytoplasmic antibodies (ANCA) and SSA positivity were more common in late onset LN patients. The patients with hypertension in late onset LN were much more than that in control group. The renal histological classes showed no significant difference between the two groups. Leukopenia and serum ANCA were more common. The results suggest a more severity of the disease in late onset LN.     

Serum interleukin-18 levels in patients with systemic lupus erythematosus: Relation with disease activity and lupus nephritis

Aim of the workTo further investigate the possible role of IL-18 in the pathogenesis of systemic lupus erythematosus (SLE) and development of lupus nephritis (LN), and to explore its relationship with pathological classes of LN, degree of acute renal activity and chronic damage.Patients and methodsForty-one SLE patients with LN, thirty-one lupus non-nephritis patients and fifteen age and sex matched healthy controls were enrolled in this study. SLE patients were subjected to disease activity assessment by SLEDAI, renal disease activity assessment by the Systemic Lupus International Collaborating Clinics (SLICC) Renal Activity Score, laboratory investigations including measurement of serum interleukin-18 using Enzyme Linked Immunosorbent Assay. Renal biopsy was obtained from LN patients and pathological classification was made according to World Health Organization (WHO) criteria. Analysis of activity and chronicity indices was done on these biopsy specimens.ResultsSerum levels of IL-18 were significantly higher in patients with LN than lupus non-nephritis patients and healthy controls (p < 0.001). There were significant correlations between IL-18 and SLEDAI (p = 0.002), proteinuria (p = 0.027), renal activity score (p = 0.003) and activity index (p = 0.039) in patients with LN. There was no significant difference in the serum levels of IL-18 between WHO classes of LN.ConclusionIL-18 appears to have a pathogenic role in the development of SLE and plays a crucial role in triggering inflammation in LN. Serum IL-18 levels could be a useful biomarker to assess the activity of renal disease in SLE.     

Time of initial appearance of renal symptoms in the course of systemic lupus erythematosus as a prognostic factor for lupus nephritis

The prognosis of lupus nephritis (LN) was studied retrospectively in two LN categories, LN manifested initially at systemic lupus erythematosus (SLE) onset (I-LN) and LN of delayed manifestation after SLE onset (D-LN), based on a chart review (C) of 154 SLE (85 LN) patients with a mean observation of 20.8 ± 9.3 years and a questionnaire study (Q) of 125 LN patients outside our hospital with mean observation of 17.6 ± 9.2 years. In both study groups, half of I-LN patients were relapse-free by Kaplan–Meier analysis after initial therapy, and the relapsed I-LN patients responded to retherapy at higher 5-year relapse-free rates than those of patients receiving initial therapies for D-LN. At last observation, a higher frequency of prolonged remission was shown in I-LN compared with D-LN patients (C: 22/31, 71% versus 14/49, 29%, P < 0.01; Q: 65/89, 73% versus 11/33, 33% P < 0.01) and also a higher frequency of irreversible renal damage in D-LN compared with I-LN patients (C: 25/49, 51% versus 2/31, 6%, P < 0.001; Q: 14/33, 42% versus 6/89, 7%, P < 0.001), although class IV pathology was common in patients (C) in both LN categories. Onset time of lupus nephritis in the course of SLE may affect renal prognosis.     

Outcome of lupus renal disease in the past two decades: a report from China

Objective: To evaluate the differences in the renal survival of lupus nephritis (LN) diagnosed either during 1985–1994 or 1995–2004 and to analyse the possible causes. Methods: Fifty‐two patients with biopsy‐confirmed LN were followed up between 1985 and 1994 and 130 patients were followed up between 1995 and 2004. Renal survival was studied with Kaplan‐Meier analysis and the log rank test. Status at diagnosis and treatment schedules were also analysed. Results: Renal survival was significantly better in the patients who were diagnosed between 1995 and 2004 (P = 0.0233). The mean time from initiation until first diagnosis of SLE, from the initiation of SLE until referral to our centre, and from first detection of proteinuria until kidney biopsy was significantly shorter in the later decade (P < 0.05). In the decade from 1995 to 2004 there was significantly lower rates of early renal dysfunction and fewer histological signs of chronicity at the time of diagnosis of LN than in the decade from 1985 to 1994. In treatment schedules, more patients received intravenous cyclophosphamide (CTX) in a bolus in the later decade group (P = 0.014). Besides CTX, some new immunosuppressive agents such as cyclosporin A or mycophenolate mofetil were received by more patients in the decade from 1995 to 2004. Conclusions: The outcomes for patients with LN was significantly better between 1995 and 2004 than between 1985 and 1994. The result is maybe attributable to earlier diagnosis, earlier treatment, intravenous bolus CTX and more immunosuppressive agents from which to select.     

Lupus nephritis among 624 cases of systemic lupus erythematosus in Riyadh, Saudi Arabia

The aim of this article is to study the prevalence, clinicolaboratory features, WHO histological types, therapy and renal outcome of lupus nephritis (LN) in Saudi Arabia. During the 27-year-period (1980–2006), 299 (47.9%) cases of LN were identified among the 624 cases of systemic lupus erythematosus (SLE) follow-up at King Khalid University Hospital, Riyadh. The female:male ratio in LN was 8.3:1, with a mean age of 32 years and a mean age of onset of 23 years. The WHO renal histological types were; Class I (1%), Class II (18.1%), Class III (10%), Class IV (37.1%), Class V (11.7%), and Class VI (2.7%). Azathioprine was given to 43.1% and pulse cyclophosphamide to 65.6% in combination with other drugs. Remission was seen in 226 (75.6%) patients, renal flares in 14 (4.7%), end stage renal disease (ESRD) in 27 (9.0%), death in 18 (6.0%), and 14 (4.7%) lost follow-up. The 5- and 10-year patient survival rates in our whole LN cohort by Kaplan–Meier analysis were 96% and 95%, respectively. The survival did not differ significantly in different LN classes nor did it differ significantly during the three periods of presentation (1980–1990, 1991–2000, and 2001–2006; P > 0.05). The risk factors for poor survival were found to be older age at onset (>50-years age; P = 0.034), ESRD (P = 0.000), and low C3 (P = 0.022). The risk factors for progression to ESRD were older age at onset (>50-years age; P = 0.037), hypertension (P = 0.009), elevated serum creatinine (P = 0.000), and proliferative LN (Classes III, IV; P = 0.013, P = 0.039). Different treatment modalities did not have significant effect on survival in the whole LN cohort (P = >0.05). However, pulse cyclophosphamide favored remission in Classes II, III, IV, and V (P = 0.023). The main causes of death were renal failure (50%) and infections (44.4%).     

Implications of blood indices in systemic lupus erythematosus patients: Two feasible determinants of disease activity and lupus nephritis

Aim of the workTo investigate whether or not neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may by indicators of disease activity in systemic lupus erythematosus (SLE) with and without lupus nephritis (LN).Patients and methodsThis research was carried out on 40 adult SLE patients (20 with LN and 20 without) and 20 controls. The NLR and PLR were calculated. The SLE disease activity index (SLEDAI) was assessed.ResultsThe mean age of the patients was 36.2 ± 7.6 years, 38 females and 2 males (F:M 19:1), with a disease duration of4.3 ± 1.2 years. The mean SLEDAI was 15.1 ± 4.7 being significantly higher in those with LN (17.5 ± 3.5) compared to those without (12.6 ± 4.6) (p = 0.001). The mean NLR (6.1 ± 2.1) and PLR (236.6 ± 86.9) were significantly increased in patients compared to the control (2.7 ± 1.2 and 125.2 ± 38.8 respectively) (p < 0.001). The NLR and PLR were both significantly related to the serum creatinine (r = 0.35, p = 0.03 and r = 0.5, p = 0.001) and SLEDAI (r = 0.36, p = 0.03 and r = 0.34, p = 0.03 respectively). NLR can significantly predict activity of SLE at cut off 5.6 with a sensitivity 80%, specificity 65% (p = 0.007) and PLR at cut off 217 with sensitivity 75%, specificity 65% (p = 0.035). The NLR can significantly predict LN at cut off 3.6 (sensitivity 80%, specificity 40%; p = 0.007) and PLR at cut off 186 (sensitivity 70%, specificity 60%; p = 0.035).ConclusionThere is a remarkable link between PLR and NLR with SLEDAI. Thus, both may serve as promising affordable indicators of inflammation in SLE. The notable relation to LN may signal renal involvement in patients with SLE.     

Serum level of galectin-9 in systemic lupus erythematosus patients with lupus nephritis: Relation to clinical characteristics and disease activity

Aim of the workTo assess galectin-9 (Gal-9) level in the serum of systemic lupus erythematosus (SLE) patients with and without renal involvement and clarify its relation with disease activity.Patients and methods50 SLE patients; 25 with lupus nephritis (LN) and 25 without as well as 25 controls were studied. Systemic Lupus International Collaborating Clinics (SLICC) renal activity score and SLE disease activity index 2000 (SLEDAI-2 K) were determined. Serum Gal-9 was measured in all participants.ResultsGal-9 level was significantly elevated in SLE patients with (16.7; 11.6–33.7 ng/ml) and without (15.9; 11.8–25 ng/ml) compared to controls (3.9; 2.8–5.4 ng/ml) (p < 0.001) but was comparable between the patients groups (p = 0.83). In LN patients, serum Gal-9 and SLICC renal activity score significantly correlated (r = 0.48, p = 0.016). Serum Gal-9 significantly correlated with SLEDAI-2 K in patients with (r = 0.71, p < 0.001) and without (r = 0.95, p < 0.001) LN, with anti-double stranded deoxyribonucleic acid (anti-ds-DNA) titers (with r = 0.57, p < 0.001 and without r = 0.79, p < 0.001) and inversely with C3 (with r = -0.44, p = 0.027 and without r = -0.63, p < 0.001) and C4 (with r = -0.47, p = 0.018 and without r = -0.43, p = 0.03). Gal-9 had an area under the curve (AUC) of 0.96 to distinguish SLE cases from control. However, AUC between LN group and non-nephritic SLE was 0.48. On regression, SLEDAI-2 K was the only significant factor associated with serum Gal-9 (p < 0.001).ConclusionIn SLE patients, significantly raised Gal-9 levels and relation with disease activity were detected indicating its clinical relevance as biomarker of disease activity and its potential value in the disease diagnosis. Its value in discriminating LN from non-nephritic SLE is limited.     

Anti-dsDNA antibodies in Brazilian patients of mainly African descent with systemic lupus erythematosus: lack of association with lupus nephritis

Renal disease is associated with morbidity and mortality in systemic lupus erythematosus (SLE) and anti-dsDNA antibodies with SLE immunopathogenesis. We investigated the dsDNA antibody profile of 84 Brazilian SLE patients, 27 with lupus nephritis. Thirty-six (39.1%) patients had dsDNA IgG antibodies shown in enzyme-linked immunosorbent assay (454.7 ± 281.1 WHO units/mL), nine presenting renal disease. The following profile of dsDNA antibodies was demonstrated in Crithidia luciliae test: IgA (seven out of 36; 19.4%), IgG (22 out of 36, 66.1%); IgM (nine out of 36, 25.0%), and IgE (four out of 36, 11.1%). Two or three isotypes of dsDNA antibodies were observed in nine (25.0%) patients, while 11 (30.5%) were seronegative in the C. luciliae test. Patients with dsDNA antibodies had lower serum C3 and C4 when compared with SLE individuals without these immunoglobulins (P < 0.01 and P < 0.001, respectively). There was no association between any dsDNA antibody isotype and lupus kidney disease nor was anti-dsDNA IgM antibody associated with absence of nephritis.     

Clinical utility of urinary soluble CD163 in evaluation of lupus nephritis patients

Aim of the workTo assess urinary soluble CD163 (sCD136) in systemic lupus erythematosus (SLE) patients compared to healthy controls. In addition to determine its association with different SLE clinical features, laboratory investigations and pathological indices focusing on those suggest renal disease activity.Patients and methodsThe study included 58 SLE patients and 30 controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active lupus nephritis (ALN) (renal SLEDAI ≥ 4) and no-renal activity (NRA) SLE patients (renal SLEDAI = 0). Urinary sCD163 was measured by Enzyme-Linked Immunosorbent Assay (ELISA). Urine values were normalized to urinary creatinine excretion. Renal biopsies were performed in 21 ALN patients.ResultsThey were 54 females and 4 males with a mean age 31.8 ± 9.1 years and disease duration 6.2 ± 4.8 years. They were 31 with ALN and 27 NRA SLE patients. Urinary sCD163 level was significantly higher in SLE patients (1.85 ± 0.3) than controls (0.5 ± 0.36, p < 0.001). In ALN, it was significantly higher (2.91 ± 2.52) compared to NRA SLE patients (0.64 ± 0.38) and controls (p < 0.001 in both). The optimum cut-off value above which normalized urinary sCD136 can predict renal activity was > 0.82 with sensitivity of 90.3%, specificity of 88.89%, p < 0.001. Urinary sCD163 significantly correlated with renal (r = 0.75, p < 0.001) but not with extra-renal SLEDAI. It correlated with activity index of renal biopsy (r = 0.46, p = 0.038).ConclusionUrinary sCD163 is a potential biomarker for LN activity. Its level is associated with clinical features, laboratory investigations and pathological indices that indicate renal disease activity.     

Antinucleosome antibodies as a potential biomarker for the evaluation of renal pathological activity in patients with proliferative lupus nephritis

The objective of this study is to evaluate the correlation between antinucleosome antibodies and renal pathological activity in patients with proliferative lupus nephritis (LN). We evaluated 36 patients with proliferative LN, 14 non-renal lupus patients and 10 healthy volunteers. Lupus activity was assessed using the British Isles Lupus Assessment Group 2004 (BILAG 2004) index, serum anti-double stranded DNA (anti-dsDNA) levels, serum complement levels and daily urinary protein levels. All 36 lupus nephritis patients received renal biopsy. Antinucleosome antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Our results showed that levels of serum antinucleosome antibodies were significantly higher in LN patients (median 90.35 units/ml, interquartile range [IQR] 37.38-135.23) than in non-renal SLE patients (median 5.45 units/ml, IQR 2.6-28.93, p <0.05) and in healthy volunteers (median 3.35 units/ml, IQR 2.95-5.23, p <0.001). Serum levels of antinucleosome antibodies were positively correlated with BILAG index (Spearman's r = 0.645, p <0.001) and serum anti-dsDNA antibody levels (r(s) = 0.644, p <0.01), while serum levels of antinucleosome antibodies were negatively correlated with serum levels of C3 (r(s) = -0.400, p <0.01) and C4 (r(s) = -0.300, p <0.05). Serum levels of antinucleosome antibodies were positively correlated with the histological activity index of LN (r(s) = 0.368, p <0.05). However, there was no significant correlation between serum levels of antinucleosome antibodies and the histological chronicity index. In conclusion, the serum level of antinucleosome antibodies is a potential biomarker for early recognition of renal involvement and evaluation of disease activity in SLE. Our preliminary results suggested that serum levels of antinucleosome antibodies might be a potential biomarker in evaluating pathological activity of LN.     

Evaluation of visfatin in patients with systemic lupus erythematosus: Correlation with disease activity and lupus nephritis

IntroductionRenal involvement affects about 50% of SLE patients accounting for significant morbidity and mortality in these patients. The adipokine “visfatin” acting as a growth factor for B-lymphocyte-precursors, exerts several proinflammatory functions. It was demonstrated as a marker of endothelial dysfunction (ED) in chronic kidney disease (CKD) thus could be a factor linking inflammation in SLE and kidney disease.Aim of the workTo assess serum visfatin level in SLE patients and its correlation to disease activity and lupus nephritis (LN) in these patients.Patients and methodsSerum level of visfatin using enzyme-linked immunosorbent assay (ELISA), chemical and immunological markers of SLE and LN were measured in 40 SLE patients and 40 age and sex matched healthy controls. Disease activity and renal involvement were assessed using SLE Disease Activity Index (SLEDAI) and Renal SLEDAI respectively further dividing patients into active versus inactive and LN versus non-LN respectively. Renal biopsies were taken from LN subgroup and were classified according to the modified WHO classification.ResultsA significantly higher serum visfatin level was found on comparing SLE patients (mean 109 ± 180 ng/ml, median18) with controls (mean 9.4 ± 11 ng/ml, median2.5) with statistically highly significant difference (z = 5.2, P < 0.001). Also there was a statistically significant difference as regards serum visfatin level between active SLE patients (mean 173 ± 111 ng/ml, median 14) and inactive patients (mean 139 ± 88 ng/ml, median 5) (z = 2.1, P < 0.05) as well as between patients with LN (mean 226 ± 180 ng/ml, median18) and patients with no LN (mean 101 ± 140 ng/ml, median 8(2-229)) (z = 2.1, P < 0.05). Visfatin had a highly significant positive correlation with disease duration (r = 0.48, P < 0.001), SLEDAI (r = 0.62, P < 0.001) as well as ESR, CRP and, renal score (r = 0.45, 0.35, and 0.65, respectively) while inverse correlation with estimated GFR (r = ?0.614) and C3 and C4 titre (r = ?0.26, r = ?0.35, respectively) was recorded. Visfatin showed high sensitivity in detecting active SLE and LN 83% and 85%, respectively.ConclusionSerum visfatin is strongly associated with LN in SLE patients and is a promising biomarker for prediction of renal involvement in these patients. It reflects SLE activity specially LN activity namely renal score and GFR decline. Further prospective studies are required to confirm visfatin as a destructive mediator of predictive and prognostic value in active lupus nephritis.     

Vitamin D may not be a good marker of disease activity in Korean patients with systemic lupus erythematosus

Vitamin D is a pleiotrophic hormone with immunoregulatory properties. Low levels of vitamin D have been discovered in various autoimmune diseases. Here, we investigated serum vitamin D levels in Koreans with systemic lupus erythematosus (SLE) and examined whether levels correlate with disease activity of SLE. Blood samples were prospectively collected from patients with SLE (n = 104) and normal controls (NC, n = 49) during the spring from March to May 2008. The level of serum 25-hydroxyvitamin D (25(OH)D3) was measured by radioimmunoassay. The serum 25(OH)D3 levels of patients with SLE (42.49 ± 15.08 ng/ml) were significantly lower than NC (52.72 ± 15.19 ng/ml, P < 0.001). Additionally, 17 patients with SLE (16.3%) had vitamin D insufficiency, while two NC had vitamin D insufficiency (4.1%). The risk of vitamin D insufficiency was 4.6-fold increased in SLE (P = 0.032). The serum 25(OH)D3 levels, adjusted with BMI, were positively correlated only with hemoglobin (β = 0.256, P = 0.018) and serum complement 3 (β = 0.365, P = 0.002). Serum vitamin D levels were lower, and vitamin D insufficiency was more common in Korean patients with SLE, however, our study demonstrated that vitamin D levels might not be a good marker of disease activity.     

Anti-dsDNA,anti-Sm antibodies,and the lupus anticoagulant: significant factors associated with lupus nephritis

BACKGROUND: Lupus nephritis (LN) is a common manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies and ethnicity have been associated with LN, but the results are controversial. OBJECTIVE: To study the immunological and demographic factors associated with the development of LN. PATIENTS AND METHODS: A retrospective case-control study of 127 patients with biopsy-proven LN, and 206 randomly selected patients with SLE without nephritis as controls was designed. All patients had attended our lupus unit during the past 12 years. Standard methods were used for laboratory testing. RESULTS: Patients with LN were significantly younger than the controls at the time of SLE diagnosis (mean (SD) 25.6 (8.8) years v 33.7 (12.5) years; p<0.0001). The proportion of patients of black ethnic origin was significantly higher in the group with nephritis (p=0.02). There were no differences in sex distribution or duration of follow up. A higher proportion of anti-dsDNA, anti-RNP, anti-Sm, and lupus anticoagulant (LA) was seen in the group with nephritis (p=0.002; p=0.005; p=0.0001; p=0.01, respectively). In univariate, but not in multivariate, analysis male sex and absence of anti-dsDNA were associated with earlier onset of renal disease (p=0.03; p=0.008). In multivariate analysis the only factors associated with nephritis were younger age at diagnosis of SLE, black race, presence of anti-dsDNA, anti-Sm, and LA. No demographic or immunological associations were seen with WHO histological classes. CONCLUSIONS: Young, black patients with anti-dsDNA, anti-Sm antibodies, and positive LA, appear to have a higher risk of renal involvement. These patients should be carefully monitored for the development of LN.