Oxidative stress, inflammation and disease activity biomarkers in lupus nephropathy

Lupus ◽  
2020 ◽  
Vol 29 (3) ◽  
pp. 311-323 ◽  
Author(s):  
N Bona ◽  
E Pezzarini ◽  
B Balbi ◽  
S M Daniele ◽  
M F Rossi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Interleukin 6 ◽  
Oxidative Stress Biomarkers ◽  
Active Lupus Nephritis ◽  
Renal Tubular ◽  
Active Lupus

Lupus nephropathy is a severe and frequent complication of systemic lupus erythematosus. Here, we assessed the biomarkers of oxidative stress, inflammation and disease activity in patients with lupus nephritis. Thirty-four patients with active lupus nephritis, 31 patients with inactive lupus nephritis and 20 lupus patients without renal damage (non-lupus nephritis) were studied. Oxidative stress biomarkers malonyldialdehyde, oxidized-to-total glutathione, catalase, superoxide dismutase and total antioxidant status were assessed, as well as inflammation biomarkers CRP, interleukin 6 and monocyte chemoattractant protein 1. Renal tubular disease biomarkers neutrophil gelatinase-associated lipocalin and β2-microglobulin were assessed, together with the classic disease activity biomarkers urinary protein/creatinine ratio, anti-dsDNA, anti-C1q antibody and complement proteins C3 and C4. Significant differences were found between active lupus nephritis and inactive lupus nephritis patients and between active lupus nephritis and non-lupus nephritis patients for all the assessed biomarkers ( P < 0.05), except for catalase, superoxide dismutase and interleukin 6. There is an imbalance in the redox status in active lupus nephritis patients that would be involved in lipid peroxidation of the glomerular basal membrane that would alter its integrity and could also affect renal tubular function in these patients.

scholarly journals The association between serum prolactin levels and interleukin-6 and systemic lupus erythematosus activity

Reumatismo ◽  
2018 ◽  
Vol 70 (4) ◽  
pp. 241-250 ◽  
Author(s):  
W.A. Wan Asyraf ◽  
M.S. Mohd Shahrir ◽  
W. Asrul ◽  
A.W. Norasyikin ◽  
O. Hanita ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Prolactin Level ◽  
Serum Prolactin ◽  
Systemic Lupus ◽  
Serum Prolactin Level ◽  
Active Lupus Nephritis ◽  
Active Lupus

Based on the recent evidence of association between hyperprolactinemia and systemic lupus erythematosus disease activity (SLEDAI), a study was conducted to analyze the association of hyperprolactinemia with lupus nephritis disease activity. In this cross-sectional study, the analysis was conducted on SLE patients who visited the University Kebangsaan Malaysia Medical Centre (UKMMC) Nephrology Clinic from August 2015 till February 2016. The disease activity was measured using the SLEDAI score, with more than 4 indicating active lupus nephritis. Basal resting prolactin level was analyzed in 43 patients with lupus nephritis, in 27.9% of them had raised serum prolactin. The median of serum prolactin level at 0 minutes was 19.91 ng/mL (IQR: 15.95-22.65 ng/ mL) for active lupus nephritis, which was significantly higher compared to the median of serum prolactin level of 14.34 ng/mL (IQR: 11.09-18.70 ng/mL) for patients in remission (p=0.014). The serum prolactin level positively correlated with SLEDAI (rhos: 0.449, p=0.003) and the UPCI level in lupus nephritis patients (rhos: 0.241, p=0.032). The results were reproduced when the serum prolactin was repeated after 30 minutes. However, the serum prolactin levels at 0 minutes were higher than those taken after 30 minutes (p=0.001). An assessment of serum IL-6 levels found that the active lupus nephritis patients had a higher median level of 65.91 pg/ mL (IQR: 21.96-146.14 pg/mL) compared to the in-remission level of 15.84 pg/mL (IQR: 8.38-92.84 pg/mL), (p=0.039). Further correlation analysis revealed that there was no statistical correlation between the interleukin (IL)-6 levels with serum prolactin, SLEDAI and other lupus nephritis parameters. An ROC curve analysis of serum prolactin at 0 minutes and serum prolactin after 30 minutes and IL-6 levels for prediction of SLE disease activity provided the cutoff value of serum prolactin at 0 minutes, which was 14.63 ng/mL with a sensitivity of 91.7% and specificity of 58.1% and AUC of 0.74 (p=0.015). This study concurred with the previous findings that stated that hyperprolactinemia is prevalent in SLE patients and correlated with clinical disease activity and UPCI level. The baseline of the fasting serum prolactin level was found to be a sensitive biomarker for the evaluation of lupus nephritis disease activity.

Urinary C3d is elevated in patients with active Lupus nephritis and a fall in its level after 3 months predicts response at 6 months on follow up

Lupus ◽  
2020 ◽  
Vol 29 (13) ◽  
pp. 1800-1806
Author(s):  
Sujata Ganguly ◽  
Sanjukta Majumder ◽  
Sandeep Kumar ◽  
Ranjan Gupta ◽  
Hafis Muhammed ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Degradation Products ◽  
Activity Index ◽  
Complement C3 ◽  
Induction Treatment ◽  
Significant Fall ◽  
Active Lupus Nephritis ◽  
Active Lupus

Introduction Complement activation is central to the pathogenesis of lupus nephritis (LN). Low serum complement C3 and C4, are traditionally used as markers of lupus disease activity in general and LN in particular. In this study we prospectively measured plasma and urine C3d and C4d, degradation products of C3 and C4 corrected to creatinine in a cohort of biopsy proven LN in a longitudinal fashion for its correlation with disease activity. Methods Twenty eight biopsy proven active lupus nephritis (AN) were recruited along with four inactive nephritis (IN) and 10 healthy controls (HC). Plasma and urine were collected at baseline, prior to induction treatment and 3 months later. Clinical measures of disease activity, Systemic lupus erythematosus disease activity index 2000 (SLEDAI 2K), renal SLEDAI, serum C3, C4 and antibodies to ds DNA, urine protein and creatinine excretion (UP/UC) were collected. Plasma and urine C3d and C4d were measured using ELISA and normalized to spot urine creatinine value. Results Twenty eight AN of median age of 26.5 (20–31.50) years and disease duration of 3 (0.7–5) years were enrolled. The median urinary C3d/creatinine before treatment was 388.20 (48.98–1296) ng/mg which fell significantly to 62.69 (28.04–502.4) ng/mg at 3 months followup (p-0.01). The baseline values for the active renal disease was significantly different from IN group (9.9 (4.5–46.53 ng/mg) p-0.00). Treatment responders (partial and complete) at 6 months showed a significant fall in urinary C3d at 3 months whereas non responders had a non significant change in value. There was a significant correlation of urine C3d/creatinine with SLEDAI2K (r-0.433, p-0.00), renal SLEDAI (r-0.356, p-0.00), UP/UC ratio (r-0.489, p-<0.0001) but no significant correlation with C3 or C4. There was a significant fall in the median values of plasma C3d from 791.1 (516.0.00–1550.43) µg/ml to 338.52 (211.35–525.82) (p-0.00) µg/ml at the end of 3 months. The values showed a significant correlation with SLEDAI 2K, renal SLEDAI, UP/UC along with a significant negative correlation with C3 and C4. Conclusion Urinary C3d/creatinine levels and plasma C3d levels can be used as biomarker of disease activity and treatment response.

scholarly journals The role of Dickkopf-1 as a biomarker in systemic lupus erythematosus and active lupus nephritis

2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Mervat E. Abdelazeem ◽  
Marwa I. Abdelhaleem ◽  
Rabab A. Mohamed ◽  
Enas A. Abdelaleem
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Renal Diseases ◽  
Systemic Lupus ◽  
Active Lupus Nephritis ◽  
Active Lupus

Abstract Background Systemic lupus erythematosus (SLE) is a chronic disease which is mainly attributed to autoantibodies, cytokines, and immune complex deposition. Studies have demonstrated that cytokines and autoantibodies were strongly associated with renal diseases and can be used for the prediction of patients with lupus nephritis (LN). However, antibodies to dsDNA and the reduction of complements were also detected in non-LN patients as well as clinically non-active SLE patients. The current study was performed to detect the role of serum DKK-1 as a biomarker for the identification of SLE patients and patients with LN and its relation to disease activity and severity. The study was conducted on fifty clinically diagnosed SLE patients who were diagnosed according to Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE, in addition to thirty healthy control volunteers matched for age and sex. Assessment of SLE disease activity was done using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Assessment of SLE disease severity was done using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index. Serum levels of DKK-1 were measured for all participants by ELISA using commercially available kits. Results DKK-1 serum levels were significantly higher among active lupus nephritis cases as compared with SLE cases with no LN and with healthy controls (9197.60 μg/uL ± 2939.2 μg/uL vs. 6405.15 μg/uL ± 2018.91 μg/uL vs. 2790.33 μg/uL ± 833.49 μg/uL) respectively (p-values < 0.001). DKK-1 concentration was significantly higher among SLE patients with positive as compared with negative anti-double-stranded DNA (dsDNA) antibodies (p-value < 0.001). According to receiver operating characteristic (ROC) curve analysis, serum DKK-1 level diagnosed the SLE at a statistically significant level with a 98% sensitivity and 70% specificity and serum DKK-1 level also diagnosed active lupus nephritis at a 90% sensitivity and 63% specificity. Conclusion DKK-1 could diagnose SLE and lupus nephritis with high sensitivity and specificity. Serum DKK-1 is a reliable biomarker for the identification of SLE and patients with LN and could be used as a key molecule for the diagnosis of SLE and as a prognostic indicator of LN.

scholarly journals SAT0234 SERUM AXL, FERRITIN, IGFBP4 AND STNFR2 AS BIOMARKERS OF PEDIATRIC SLE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1059.1-1060
Author(s):  
S. Soliman ◽  
A. Haque ◽  
S. Mason ◽  
L. Greenbaum ◽  
M. J. Hicks ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Disease Activity ◽  
Serum Ferritin ◽  
Lupus Erythematosus ◽  
Serum Markers ◽  
Protein Markers ◽  
Active Lupus Nephritis ◽  
Proteomic Screening ◽  
Active Lupus ◽  
Pediatric Sle

Background:Proteomic screening is an efficient approach for identifying protein biomarkers in various inflammatory diseases. Our preliminary proteomic analysis revealed elevated levels of serum Axl, Ferritin, IGFBP4 and sTNFR2 in adult patients with active lupus nephritis (LN) (1). However, the role of these serum biomarkers in pediatric systemic lupus erythematosus (SLE) patients has not been examined.Objectives:To evaluate the performance of 4 serum protein markers for detecting disease activity in pediatric patients with SLE.Methods:83 pediatric patients who fulfilled ≥4 ACR criteria for SLE and 25 healthy controls were recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP4 and sTNFR2. SLE disease activity was assessed using the SLEDAI-2k score, renal disease activity was assessed by the renal SLEDAI (range 0-16; 0= inactive LN, ≥ 8= active renal). 57 patients had clinically active SLE (SLEDAI score ≥ 4 or having a flare) (28 active renal and 29 active non-renal SLE patients). In active renal patients, concurrent renal biopsy was performed, unless contraindicated. The ISN/RPS criteria were used to assess the histopathologic features of LN. Those Patients were further subcategorized into 2 groups; active proliferative (ISN/RPS classes III/IV) and non-proliferative (classes I/II/V).Results:The serum concentrations of Axl and ferritin were significantly higher in patients with active SLE than inactive SLE (3765±235 vs. 2513±130 pg/ml,P= 0.001) and (111±26 vs. 18±4 ng/ml,P =0.0001) respectively. Serum Axl levels were significantly higher in active renal versus active non-renal SLE patients (3765±235.3 vs. 2825±200.7 pg/ml,P= 0.04). In the active renal patients with paired kidney tissue and blood samples, none of the biomarkers tested discriminated classes of LN, although serum Axl, ferritin and IGBPB4 levels were higher in the proliferative subgroup. The levels of Axl, ferritin and IGFBP4 correlated significantly with SLEDAI scores (Axl, r= 0.58,P<0.0001; ferritin, r= 0.53,P<0.0001; IGFBP4, r= 0.229,P= 0.03). However, only serum Axl levels correlated significantly with the renal SLEDAI (r= 0.46,P= 0.01). The levels of Axl, IFGBP4 and sTNFR2 correlated with decreased C3 levels (r= - 0.54,P<0.0001; r= - 0.29,P= 0.007; r= - 0.29,P= 0.007) respectively. Only serum Axl and ferritin correlated with urinary PCR (r= 0.42,P<0.0001; r= 0.22,P=0.04) respectively. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA or decreased C3. The specificity values of serum ferritin and IGFBP4 for concurrent active lupus nephritis were higher than anti-dsDNA or C3. Serum ferritin was the best predictor of global SLE activity (AUC 0.81,P<0.0001), followed by C3 (AUC 0.79,P<0.0001) then Axl (AUC 0.71,P= 0.002), while both Axl and C3 were the best predictors of lupus nephritis activity (AUC 0.72, both).Conclusion:In pediatric SLE patients, serum ferritin and Axl perform better than traditional yardsticks in identifying disease activity, either global or renal. The performance of these serum markers should be explored further in a longitudinal cohort of pediatric SLE patients.References:[1]Wu T, Ding H, Han J, et al. Antibody-Array-Based Proteomic Screening of Serum Markers in Systemic Lupus Erythematosus: A Discovery Study. J Proteome Res. 2016 Jul 1;15 (7): 2102-14.Disclosure of Interests:None declared

scholarly journals THU0239 DYNAMIC TEMPORAL CHANGES IN CLINICAL DISEASE ACTIVITY AND GUT MICROBIOTA REPRESENTATION OF A PATHOBIONT LINKED TO LUPUS NEPHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 346.2-347
Author(s):  
G. Silverman ◽  
D. Azzouz ◽  
Z. Chen ◽  
J. Deng ◽  
Z. Li ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
16S Rrna ◽  
Disease Activity ◽  
Immune Activation ◽  
Clinical Disease ◽  
Whole Genome ◽  
Pilot Studies ◽  
Clinical Disease Activity ◽  
Active Lupus Nephritis ◽  
Active Lupus

Background:From a cross-sectional cohort, we have identified a candidate human gut anaerobic pathobiont,Ruminococcus gnavus(RG) of the familyLachnospiraceaethat was linked to active Lupus nephritis (LN)(1). Based on 16S rRNA amplicon analysis, LN patients displayed increased fecal RG abundance, concordant with serum IgG anti-RG antibody responses that appeared intertwined with anti-dsDNA responses implicated in renal pathogenesis. Indeed, monocolonization of germ-free mice is reported to result in generalized inflammation and expansions of Th17 cells. However, RG at low levels are also prevalent in healthy adults, and the temporal dynamics of RG representation within Lupus microbiota ecosystems have not been investigated. Also, genomic sequences of few RG strains have been reported, and these vary greatly in genome structure, gene representation and sequence, which may have broad implications for adaptation to a host with systemic inflammation and/or factors that contribute to immune activation in a susceptible host.Objectives:To investigate the relationships betweenin vivoRG expansions and disease activity that often wax and wane overtime, we initiated longitudinal studies in Lupus patients and controls. As representation of RG strains alone might alter pathogenic potential, we also sought to characterize RG strains from active LN patients.Methods:From our cohort, patients were characterized for demographics, clinical disease activity, and serologies including standard autoantibody and complement levels, and anti-bacterial responses of interest. High throughput 16S rRNA amplicon libraries from fecal samples were analyzed using QIIME 2 and DADA2 (1). Also, individual RG colonies were isolated and subjected to whole genome sequencing. Species and strains were then assigned in part based on multi-locus sequence typing and reference guided genomic assemblies.Results:16S rRNA analysis of 34 samples, at 2-4 timepoints from 14 SLE patients, documented highly conserved patterns of gut community representation overtime in 10/14 patients, based in part on unsupervised hierarchical cluster analysis. Notably, independent of vacillations in clinical disease activity of up to 8 SLEDAI points, conserved microbiome phylogenetic abundance/composition was documented at a family level, and the level of amplicon sequence variants that approximate identification of individual species. In pilot studies, from two active lupus nephritis patients hundreds of fecal bacterial colonies were isolated, with initial assignments by 16S rRNA sequence. From highly redundant whole genome sequence analysis, these Lupus-patient fecal colonies were found to distribute into only four distinct RG strains, which differed from reported strains.Conclusion:Our findings suggest that many Lupus patients have little or no detectable perturbations in representation of theLachnospiraceaefamily or abundance of RG species overtime. Moreover, this seeming microbiota stability was documented even in patients with dramatic changes in disease activity. However, these approaches are inadequate to detect shifts between RG strains. In pilot studies we have isolated and characterized the genomes of four unique RG strains from active LN patients, which include variations in gene content and sequence that may have implications for the host-commensal relationship and immune activation. Broadening of these studies to larger number of SLE patients and healthy subjects, with metagenomic surveys of strain representation in genomic shotgun libraries are currently in progress, in coordination with murine colonization testing for immune modulatory properties of individual strains.References:[1]Azzouzet al.Ann Rheum Dis2019 78(7):947-56Disclosure of Interests: :Gregg Silverman Consultant of: Work with industry is unrelated to the topic in this abstract, Doua Azzouz: None declared, Ze Chen: None declared, Jing Deng: None declared, Zhi Li: None declared, David Fenyo: None declared, Alexander Alekseyenko: None declared

scholarly journals Comparison of iguratimod and conventional cyclophosphamide with sequential azathioprine as treatment of active lupus nephritis: study protocol for a multi-center, randomized, controlled clinical trial (iGeLU study)

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Qingran Yan ◽  
Fang Du ◽  
Yuening Kang ◽  
Ping Ye ◽  
Xiaodong Wang ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Maintenance Therapy ◽  
Lupus Erythematosus ◽  
Remission Rate ◽  
Hypothesis Test ◽  
Controlled Study ◽  
Controlled Clinical Trial ◽  
Link Type ◽  
Active Lupus Nephritis ◽  
Active Lupus

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up. Methods/design This study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test. Discussion Most patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20–35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients. Trial registration ClinicalTrials.govNCT 02936375. Registered on October 18, 2016.

The Relation of Interleukin 17 (IL-17) and IL-23 to Th1/Th2 Cytokines and Disease Activity in Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (10) ◽  
pp. 2046-2052 ◽  
Author(s):  
MO YIN MOK ◽  
HAI JING WU ◽  
YI LO ◽  
CHAK SING LAU
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Interleukin 17 ◽  
Healthy Controls ◽  
Th2 Cytokines ◽  
Systemic Lupus ◽  
Active Lupus Nephritis ◽  
Active Lupus ◽  
Active Disease

Objective.Interleukin 17 (IL-17) was recently linked to pathogenesis of systemic lupus erythematosus (SLE), but its relation to disease activity has not been well characterized. We examined the relation between serum levels of Th17 (IL-17, IL-23), Th1 (IL-12, interferon-γ), Th2 (IL-10, IL-6, IL-4) cytokines and disease activity in patients with SLE.Methods.Serum cytokines were measured by enzyme linked immunosorbent assays. Disease activity was determined by SLE disease activity index (SLEDAI), anti-dsDNA antibody, and C3 and C4 levels.Results.Serum levels of IL-17 (p < 0.001), IL-6 (p = 0.006) and IL-10 (p < 0.001) were higher in SLE patients (n = 70) compared to healthy controls (n = 36). Higher serum IL-23 level was found in patients with active disease with cutaneous manifestations (p = 0.004) and serositis (p = 0.04) compared to those without. Serum IL-17 level above the detection limit was more frequently found in patients who had active lupus nephritis (11/23, 47.8%) (p = 0.002), nonrenal active disease (9/15, 60%) (p = 0.001), and inactive lupus (21/32, 65.6%) (p < 0.001) compared to healthy controls (0%). Serum IL-17 levels were otherwise comparable between these 3 groups of patients and were not related to SLEDAI, glomerular filtration rate, activity or chronicity score and ISN/RPS criteria class among patients with active lupus nephritis. There was no significant correlation between serum IL-17/IL-23 and Th1 or Th2 cytokine levels.Conclusion.SLE patients had higher serum IL-17 levels than healthy controls. Elevated serum IL-23 was found in patients with inflammatory manifestations including cutaneous involvement and serositis. The lack of correlation between Th17, Th1, and Th2 cytokines suggested independent regulatory mechanisms for these cytokines.

Annexin II-binding immunoglobulins in patients with lupus nephritis and their correlation with disease manifestations

2017 ◽  
Vol 131 (8) ◽  
pp. 653-671 ◽  
Author(s):  
Kwok Fan Cheung ◽  
Susan Yung ◽  
Mel K.M. Chau ◽  
Desmond Y.H. Yap ◽  
Kwok Wah Chan ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Cell Surface ◽  
Disease Activity ◽  
Mesangial Cell ◽  
Activity Index ◽  
Ultrastructural Localization ◽  
Annexin Ii ◽  
Proliferative Lupus Nephritis ◽  
Active Lupus Nephritis ◽  
Active Lupus

Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins (Igs) in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in New Zealand Black and White F1 mice (NZBWF1/J) mice. Annexin II-binding Igs in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis were significantly higher compared with controls (8.9%, 1.3% and 0.9% for annexin II-binding IgG and 11.1%, 4.0% and 1.9% for annexin II-binding IgM for patients with active lupus nephritis, patients with non-lupus renal disease and healthy subjects respectively). In lupus patients, annexin II-binding IgM level was higher at disease flare compared with remission. Annexin II-binding IgG and IgM levels were associated with that of anti-dsDNA and disease activity. Annexin II-binding IgG and IgM levels correlated with histological activity index in lupus nephritis biopsy samples. In NZBWF1/J mice, serum annexin II-binding IgG and IgM levels and glomerular annexin II and p11 expression increased with progression of active nephritis. Annexin II expression was present on mesangial cell surface and in the mesangial matrix, and co-localized with electron-dense deposits along the glomerular basement membrane. Our results show that circulating annexin II-binding IgG and IgM levels are associated with clinical and histological disease activity in proliferative lupus nephritis. The co-localization of annexin II and p11 expression with immune deposition in the kidney suggests pathogenic relevance.

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