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.     

The effectiveness and safety of mycophenolate mofetil in lupus nephritis

The purpose of this study is to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) for inducing and/or maintaining remission of lupus nephritis (LN). This is a retrospective study of 25 LN patients consecutively treated with MMF. The primary outcome was complete renal remission (CR) defined by urine protein/creatinine ratio ≤0.5 g/g and inactive urine sediment and serum creatinine within <15% above baseline. For induction, 21 episodes of active, moderate to severe LN were treated with MMF. Twelve cases (57%) achieved CR over a median of 8.5 months. Of 13 patients who had LN for <12 months and took ≥2 g/day of MMF, 11 achieved CR, compared to one out of the eight patients who did not meet both criteria (p = 0.0022). For maintenance therapy, 15 patients received MMF for a median of 20 months (range 5–55 months). Two patients (13%) experienced renal flares while taking MMF. Most adverse events were transient and did not require change in therapy. This study suggests that MMF is an effective treatment for both induction and maintenance of remission of moderate to severe LN with a relatively favorable safety profile. Early treatment and a dose ≥2 g/day are essential for optimal outcome. CR may take >6 months.     

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.     

Antinuclear Antibody (ANA) and ANA Profile Tests in Children with Autoimmune Disorders: A Retrospective Study

The study objective was to determine the clinical value of positive antinuclear antibody (ANA) and ANA profile tests in children with autoimmune disorders. A retrospective chart review was carried out of all patients under 18 years of age with a positive ANA test (HEp-2 cell substrate, titre ≥1:40) and ANA profile (ELISA) referred to the paediatric rheumatology service at the authors” institution between 1992 and 1996. Of 245 children with a positive ANA test, 134 (55%) had an autoimmune disease, including juvenile rheumatoid arthritis (n = 49), systemic lupus erythematosus (SLE) (n = 40) and others (n = 45). The remaining 111 patients did not have identifiable autoimmune diseases. Patients with autoimmune disorders had significantly higher ANA titres of ≥1:160 (χ²= 16, P<0.0001). In addition, of the 245 patients with a positive ANA test, 86 had an ANA profile performed; this was positive in 32 and negative in 54. All 32 patients with a positive ANA profile (100%) had an autoimmune disorder, compared to 22 ( 41%) of 54 with a negative ANA profile who had autoimmune disorders. Of 22 SLE patients with a positive ANA profile, 16 (73%) had positive anti-dsDNA and 15 (68%) had positive anti-Sm and positive anti-RNP. A positive ANA profile correlated strongly with an ANA titre ≥1:640 (χ²= 5.7 , P<0.02). The study demonstrated that only 55% of children with a positive ANA test had a definitive diagnosis of autoimmune disorder. These children tend to have higher ANA titres of ≥1:160. However, a positive ANA profile was strongly correlated with an ANA titre ≥1:640 and highly indicative of an autoimmune disorder (100%). We suggest that in order to reduce cost, an ANA profile should not be performed on all patients with positive ANA, but reserved for those with an ANA titre of ≥1:640 and/or those with a high clinical index of suspicion for autoimmune disorder, especially SLE. Received: 14 September 1999 / Accepted: 23 December 1999     

Male gender results in more severe lupus nephritis

Gender may produce different characteristics in the manifestation of systemic lupus erythematosus (SLE). The present study investigated the influence of gender on clinical, laboratory, autoantibodies and histopathological classes of lupus nephritis (LN). As much as 81 patients diagnosed with SLE (ACR criteria) and active nephritis, who underwent renal biopsy between 1999 and 2004, and who had frozen serum samples and clinical data available from the time of biopsy, were selected for this study. The presence of anti-P and antichromatin antibodies was measured using ELISA, and anti-dsDNA was measured using indirect immunofluorescence. All of the renal biopsies were reviewed in a blinded manner by the same expert renal pathologist. The charts were extensively reviewed for demographic and renal features obtained at the time of the biopsy. Of the 81 patients (13.6%), 11 were male SLE patients. Both male and female lupus patients were of similar age and race, and had similar durations of lupus and renal disease. The female patients had more cutaneous (95.7 vs. 45.5%, P = 0.0001) and haematological (52.9 vs. 18.2%, P = 0.04) involvements than the male SLE patients. In addition, the articular data, central nervous system analyses, serositis findings and SLEDAI scores were similar in both experimental groups. Positivity for anti-dsDNA, anti-ribosomal P and antichromatin did not differ between the two groups, and both groups showed similarly low C3 or C4 serum levels. Our analysis indicated that no histopathological class of LN was predominant in both males and females. Interestingly, the serum creatinine levels were higher in the male SLE patients compared to the female SLE group (3.16 ± 2.49 vs. 1.99 ± 1.54 mg/dL, P = 0.03), with an increased frequency of high creatinine (81.8 vs. 47.1%, P = 0.04) as well as renal activity index (7.6 ± 3.5 vs. 4.8 ± 3.5, P = 0.02). In addition, whilst the mean levels of proteinuria, cylindruria and serum albumin were markedly altered, they were comparable between both lupus men and women. Moreover, the frequencies of dialysis, renal transplantation and death were similar between the two groups. These data suggest that male patients had a more severe LN compared to women diagnosed with this renal abnormality.     

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.     

Anti-chromatin and anti-histone antibodies in Egyptian patients with systemic lupus erythematosus

There has been a renewed interest in anti-chromatin and anti-histone antibodies in the last few years. To assess the prevalence of anti-chromatin and anti-histone antibodies in patients with systematic lupus erythematosus (SLE) and to correlate serum levels of these antibodies with clinical features of the disease, the presence of anti-chromatin and anti-histone antibodies in 38 patients with SLE was investigated by an enzyme-linked immunosorbent assay (ELISA). To determine the specificity of these antibodies, 15 patients with rheumatoid arthritis, 15 patients with systemic sclerosis, and 15 normal controls were also tested. Sensitivity of anti-chromatin antibodies in SLE patients was 89.5% and specificity was 80.0%, while sensitivity of anti-histone antibodies was 92.1% and specificity was 82.2%. Significant associations were found between the levels of anti-chromatin antibodies and arthritis, malar rash, oral ulcer, pulmonary affection (P < 0.05) also, lupus nephritis (P < 0.01), and disease activity score as measured by SLE disease activity index (SLEDAI; P < 0.001). Significant association was found between anti-histone antibodies and fatigue (P < 0.05). The incidence of positive anti-chromatin and anti-histone antibodies was significantly higher than that of anti-dsDNA antibodies in early stage of the disease. We conclude that anti-chromatin and anti-histone antibodies are both sensitive and specific for SLE and could be a useful addition to the laboratory tests that can help in the diagnosis of SLE. Anti-chromatin antibodies seem to be a promising marker useful in early diagnosis and assessment of disease activity in SLE patients especially in patients who are negative for anti-dsDNA antibodies. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Anti-nucleosome antibodies as prediction factor of development of autoantibodies during therapy with three different TNFα blocking agents in rheumatoid arthritis

Anti-nucleosome antibodies have a role in the diagnosis and follow-up of systemic lupus erythematosus (SLE) and have a possible correlation with SLE activity and with kidney and hematological involvement. The aim of our study was to detect in 91 patients with rheumatoid arthritis (RA) the positivity of anti-nucleosome antibodies during therapy with three different TNFα blocking agents and to underline the possible correlation with the development of antinuclear autoantibodies (ANA) and anti-dsDNA autoantibodies. We detected anti-nucleosome antibodies, ANA, and anti-dsDNA during therapy with three different TNFα blocking agents at T-0 and after 12 and 24 weeks of treatment, respectively. Anti-nucleosome antibodies (IgG class) were analyzed by ELISA technique (Orgentec Diagnostika GmbH, Mainz, Germany), ANA both by indirect immunofluorescence (IIF) technique on Hep-2 (Scimedx, USA) and by ELISA (Autoimmune EIA ANA screening test Bio-Rad Laboratories, CA, USA), and anti-dsDNA (IgG and IgM classes) by ELISA (Kallestad, Bio-Rad Laboratories, CA, USA) and confirmed by IIF on Crithidia luciliae (ImmunoConcepts N.A., Sacramento, CA, USA). We observed 19 patients on infliximab treatment at 3 mg/kg every 8 weeks, 43 patients on etanercept treatment at 25 mg twice a week, and 29 patients on adalimumab treatment at 40 mg every other week. At baseline, we observed positivity as follow: in the group of patients treated with infliximab—anti-nucleosome 1/19 (5.26%), ANA 3/19 (15.7%), anti-dsDNA 1/19 (5.26%); in the group treated with etanercept—anti-nucleosome 2/43 (4.65%), ANA 1/43 (2.43%), anti-dsDNA 0/43; and in the group treated with adalimumab—anti-nucleosome 2/29 (6.89%), ANA 1/29 (3.44%), anti-dsDNA 0/29. The results at 12 weeks for the three autoantibodies were: for infliximab—3/19 (15.7%), 10/19 (52.6%), 2/19 (10.5%); for etanercept—3/43 (6.9%), 10/43 (23.2%), 1/43 (2.32%); and for adalimumab—3/29 (10.3%), 4/29 (13.7%), 1/29 (3.4%). At 24 weeks, the results were for infliximab 6/19 (31.5%), 12/19 (63.1%), 2/19 (10.5%); for etanercept 11/43 (25.5%), 22/43 (51.1%), 2/43 (4.65%); and for adalimumab 4/29 (13.7%), 13/29 (44.8%), 1/29 (3.4%). We observed a concordance anti-nucleosome/ANA antibodies of 85.5% (p < 0.001). Our data showed a concordance between anti-nucleosome antibodies and ANA positivity in patients with RA during therapy with TNFα blocking agents. The induction of autoantibodies positivity is different for each TNFα blocking agent.     

Impact of previous lupus nephritis on maternal and fetal outcomes during pregnancy

Previous reports suggest that renal involvement before pregnancy or active renal disease during pregnancy may be associated with poor fetal and maternal outcomes in systemic lupus erythematosus (SLE) women. We report our experience of fetal and maternal complications in pregnant lupus women with and without previous lupus nephritis. We analyzed the clinical records of pregnant SLE patients attended in a tertiary reference center during a 5-year period. Patients were allocated into two groups according to the presence or absence of previous lupus nephritis. Women were evaluated monthly during pregnancy and at least 1 month postpartum. Maternal and fetal outcomes of pregnancy were abstracted. We included 95 pregnancies in 92 patients. Compared with pregnant women without lupus nephritis (n = 60), pregnancies with previous lupus nephritis (n = 35) were associated with a higher risk of maternal complications (88.5% vs. 43.3%, p = 0.00001), higher rate of lupus flares (54.2% vs. 25%, p = 0.004), and renal flares (45.7% vs. 6.6%, p = 0.00001), but most of which in most instances were reversible. On the other hand, fetal outcome was similar in both groups. Multivariate analysis showed that previous lupus nephritis and active lupus at conception were predictors of adverse maternal outcome. Pregnancies in women with previous lupus nephritis had a higher rate of maternal complications in comparison with those without. However, fetal prognosis was similar in both groups.     

Clinical and serological correlates of antinucleosome antibodies in South Africans with systemic lupus erythematosus

Antinucleosome antibodies (AnuA) are increasingly recognized as an important biomarker in the diagnosis and subset stratification of patients with systemic lupus erythematosus (SLE). The aim of the study was to determine the sensitivity, specificity, and clinico-serological correlates of AnuA in black South Africans with SLE. We performed a cross-sectional study of 86 SLE patients attending a tertiary center and 87 control subjects. AnuA were tested using a second-generation enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity, positive predictive value, and negative predictive value of AnuA were 45.3, 94.3, 88.6, and 63.6%, respectively. The presence of AnuA were strongly associated with the co-presence of anti-dsDNA antibodies (OR = 3.4, p < 0.0005) and antihistone antibodies (OR = 15.7, p < 0.00001). Patients who were seropositive for AnuA were more likely to have skin involvement (discoid lupus and/or malar rash) and had higher SLE disease activity index (SLEDAI) scores and Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage scores (p < 0.05). IgG anticardiolipin antibody (aCL) levels showed a significant correlation with AnuA ratios (p < 0.01). Our findings provide further evidence that AnuA are a sensitive and specific diagnostic biomarker in SLE. Moreover, our finding that the presence of AnuA, but not anti-dsDNA antibodies, are associated with worse SLICC/ACR damage scores suggest that AnuA may have a role in predicting disease outcome. The correlation between IgG aCL and AnuA is a novel finding that merits further studies to determine possible common peptide specificities of the antibodies.     

Distal clearance margin of 1 cm or less: a safe distance in lower rectum cancer surgery

Purpose  The purpose of this study was to investigate the prognostic role of distal clearance margin (DCM) in lower rectum cancer surgery. Materials and methods  Two-hundred-three cancer patients underwent total rectal resection, possibly followed by adjuvant chemoradiotherapy. DCM was classified as positive or negative (<1, ≥1 cm) and investigated with multivariable proportional hazard models. Results  A total of 52 deaths, 19 local relapses, 40 distant metastases, and three second primaries were observed as first events. Five-year survival with positive, negative <1, or negative ≥1 cm DCM was 51%, 81%, and 69%, respectively (p = 0.018). The difference was significant between positive and negative DCM (p = 0.031), not between negative <1 and ≥1 cm (p = 0.106). Local and distant 5-year incidences according to DCM were 30%, 8%, and 8% (p = 0.006) and 38%, 26%, and 19% (p = 0.857), respectively. Conclusions  DCM, but not tumor size, is a prognostic factor after sphincter-saving surgery, which is safe whenever a negative margin is achieved.     

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.     

抗嗜中性粒细胞胞浆抗体与狼疮性肾炎的关系

目的探讨抗嗜中性粒细胞胞浆抗体（ANCA）与狼疮性肾炎（LN）临床相关表现和发病机制的关系。方法分别应用间接免疫荧光法和酶联免疫吸附分析的方法,检测81例LN患者血清中的ANCA,并分析ANCA与LN临床表现和其它实验室检查结果之间的关系。结果单用间接免疫荧光法检测时,ANCA在LN中的阳性率是30.9％（25／81）。对间接免疫荧光法检测为阳性的血清,用酶联免疫吸附分析法进行验证,结果仅有72.0％（18／25）仍为阳性,全部是核周型ANCA（p-ANCA）,未见中央型ANCA（c-ANCA）出现。ANCA阳性组LN患者合并浆膜炎、神经系统累及、贫血、抗ds-DNA抗体阳性和低补体的频率均显著高于ANCA阴性组LN患者。结论ANCA在LN中的阳性率为30.9％,并与LN特定的临床表现相关,提示ANCA可能参与了LN的发病过程。     

Lupus nephritis and Raynaud’s phenomenon are significant risk factors for vascular thrombosis in SLE patients with positive antiphospholipid antibodies

This study is aimed to determine the predictors of nongravid vascular thrombosis in systemic lupus erythematosus (SLE) patients with positive antiphospholipid antibodies (SLE-aPL). A cohort of 67 SLE-aPL patients who had at least one positive test for lupus anticoagulant (LA), anticardiolipin (aCL), or anti-beta2glycoprotein-1(B2) was examined. Main outcome was the presence of vascular thrombosis. Association between thrombosis and risk factors was examined by contingency table. The odds ratio (OR) of significant predictors was determined by logistic regression. Three percent of patients were LA⁺, 6% were aCL⁺, 31% were B2⁺, 3% were aCL⁺LA⁺, 35.8% were aCL⁺B2⁺, 7.5% were LA⁺B2⁺, and 13.4% were positive for all tests. As for clinical manifestations, 79% had lymphopenia, 76% had lupus nephritis (LN), 41.8% had autoimmune hemolytic anemia, 34.3% had thrombocytopenia, 20.9% had abortion, and 19.4% had Raynaud’s phenomenon (RP). Thrombosis occurred in 26 patients. The prevalence of thrombosis for SLE-aPL was 38.8%. Thrombosis was observed more frequently in patients with LA⁺ (12 of 18) than the others (14 of 49; p = 0.01). Two-by-two table showed that oral contraceptive and LN were significantly associated with increased risk of thrombosis, while lymphopenia and antimalarials were significantly associated with decreased risk of thrombosis. Multivariate analysis confirmed that LN and RP were associated with increased risk of thrombosis (OR = 6.2 and 3.2; p = 0.005 and 0.008), while lymphopenia and antimalarials were associated with decreased risk of thrombosis (OR = 0.86 and 0.18; p = 0.02 and 0.034). LA is the strongest test to determine the risk of thrombosis in SLE-aPL. The presence of LN and RP strongly predicts thrombosis, while lymphopenia and antimalarials are protective. These findings help to identify patients who may benefit from prophylactic therapy.     

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%).     

Rapid decrease of anti-β-glucan antibody as an indicator for early diagnosis of carinii pneumonitis and deep mycotic infections following immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis

Deep mycosis (aspergillus pneumonia (AsP)) and carinii pneumonitis (PCP) are complications of immunosuppressive treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The objective was to clarify the clinical significance of plasma titer of antibody against β-glucans (anti-BG antibody) as a predictor of complications such as AsP or PCP and the prognosis of patients. Enzyme-linked immunosorbent assay was used to measure the plasma titer of antibodies against β-glucans (BG) from Candida albicans in 22 healthy subjects and 52 patients with various stages of AAV. The mean plasma titer of the anti-BG antibody was 2,677 ± 1,686 U in healthy subjects, 691 ± 522 U in patients with untreated active vasculitis (n = 14), and 547 ± 416 U in patients soon after immunosuppressive treatment (n = 24). Healthy subjects had significantly higher antibody titers than the other two groups (P < 0.05). Repeated measurements over the clinical course of AAV revealed an increase during remission to 1,180 ± 130 U (n = 11), while there was a significant rapid decrease to 369 ± 441 U (P < 0.01) concomitantly with elevation in plasma C-reactive protein and BG levels in patients with AAV that had AsP or PCP infection. Antifungal therapy resulted in a rapid rise of anti-BG antibody titer. Experiments in mice suggested that the anti-BG antibody neutralizes BG. Rapid decrease of the anti-BG antibody titer may be a useful indicator for diagnosis of the presence of AsP or PCP and for estimating the prognosis of patients with these opportunistic infections during immunosuppressive treatment of AAV.     

Venous thromboembolism in southern Chinese patients with systemic lupus erythematosus

The objective is to study the annual incidence and standardized incidence ratio (SIR) of venous thromboembolism (VTE) in a cohort of Chinese patients with systemic lupus erythematosus (SLE). VTE events of SLE patients occurring between 1999 and 2008 were identified from our database, and the annual incidence of VTE was calculated according to the cohort size. SIRs were estimated by the ratios of the incidence of VTE in SLE to the general population. In 2008, 516 SLE patients were in our cohort. The mean age of SLE onset was 32.2 ± 14 years and the duration of SLE was 9.3 ± 8.8 years. Fifty-seven percent of the patients had disease duration of ≥5 years. Between 1999 and 2008, 18 episodes of VTE occurred in 14 patients. The incidence of VTE did not show significant fluctuation and the mean annual incidence was 4.2/1,000 patient–year. The reported VTE events were: popliteal vein thrombosis (56%), pulmonary embolism (22%), renal vein, retinal vein, subclavian vein and dural sinus thrombosis (5.6% each). The cumulative risks of VTE since SLE diagnosis were 2.8% and 3.7% at 5 and 10 years, respectively. Compared to the general population, the mean SIR of VTE in SLE patients within this period was 11.9 (7.31–19.6; p < 0.001). The SIR of VTE was highest in patients under the age of 30 years. The presence of the antiphospholipid antibody was independently associated with VTE (HR 4.36 [1.67–11.4]; p = 0.003). Although venous thrombosis is uncommon in Chinese, Chinese patients with SLE are 12 times more prone to VTE than the general population.     

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.     

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.     

Severe systemic lupus erythematosus in emergency department: a retrospective single-center study from China

This study describes the characteristics of severe systemic lupus erythematosus (SLE) patients who visited the emergency department of the Shanghai Renji Hospital, and the aim is to identify the causes, the outcome, and the prognostic factors. SLE patients who visited the emergency department between January 2007 and August 2010, and who were subsequently hospitalized or who died in emergency department, were included in this retrospective study. Of the total 131 SLE emergency events, overall mortality was 16.8%. Older age (≥45 years), longer duration of disease, presence of pulmonary hypertension, renal insufficiency, and invasive infections are risk factors. Higher organ damage index (SLICC, 3.86 ± 2.14 vs. 0.93 ± 1.14, p < 0.001) but relatively lower disease activity (SLEDAI, 11.5 ± 7.7 vs. 16.5 ± 9.0, p = 0.015) were the characteristics of the deceased when compared with the survivors. Recent-onset (duration of disease ≤3 months) SLE accounts for 32.1% of the patients in emergency, and this group showed a distinctive pattern of younger age with higher frequencies of neuropsychiatric and hematologic manifestations. A good short-term outcome with a 95.2% survival rate can be observed in such patients. Older age, longer disease duration and cumulative damage of vital organs determine the short-term outcome of severe SLE in the emergency department. Recognizing disease patterns and objective prognostic parameters may help physicians to provide better care, based on a risk-fitted approach, for the SLE patients in emergencies.