Biomarker Profiling for Lupus Nephritis

Li, Yajuan; Fang, Xiangdong; Li, Quan Zhen

doi:10.1016/j.gpb.2013.05.003

Cited by 44 publications

(27 citation statements)

References 78 publications

(75 reference statements)

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“…Although biomarkers for nephritis are being identified (5-6) there is still no reliable way of predicting an impending renal flare or determining which patients will respond to therapy. Because human renal tissue cannot be obtained sequentially during remission and relapse, animal models are often used to study progression of lupus nephritis.…”

mentioning

confidence: 99%

Identification of Stage‐Specific Genes Associated With Lupus Nephritis and Response to Remission Induction in (NZB × NZW)F1 and NZM2410 Mice

Bethunaickan

Berthier

Zhang

et al. 2014

Arthritis & Rheumatology

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Objective To elucidate the molecular mechanisms involved in renal inflammation during the progression, remission and relapse of nephritis in murine lupus models using transcriptome analysis. Methods Kidneys from NZB/W F1 and NZM2410 mice were harvested at intervals during their disease course or after remission induction. Genome wide expression profiles were obtained from microarray analysis of perfused kidneys. Real time PCR analysis for selected genes was used to validate the microarray data. Comparisons between groups using SAM, and unbiased analysis of the entire dataset using singular value decomposition and self-organizing map were performed. Results Few changes in the renal molecular profile were detected in pre-nephritic kidneys but a significant shift in gene expression, reflecting inflammatory cell infiltration and complement activation occurred at proteinuria onset. Subsequent changes in gene expression predominantly affected mitochondrial dysfunction and metabolic stress pathways. Endothelial cell activation, tissue remodeling and tubular damage were the major pathways associated with loss of renal function. Remission induction reversed most, but not all of the inflammatory changes and progression towards relapse was associated with recurrence of inflammation, mitochondrial dysfunction and metabolic stress signatures. Conclusion Immune cell infiltration and activation is associated with proteinuria onset and reverses with immunosuppressive therapy but disease progression is associated with renal hypoxia and metabolic stress. Optimal therapy of SLE nephritis may therefore need to target both immune and non-immune disease mechanisms. In addition, the overlap of a substantial subset of molecular markers with those expressed in human lupus kidneys suggests potential new biomarkers and therapeutic targets.

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mentioning

confidence: 99%

Identification of Stage‐Specific Genes Associated With Lupus Nephritis and Response to Remission Induction in (NZB × NZW)F1 and NZM2410 Mice

Bethunaickan

Berthier

Zhang

et al. 2014

Arthritis & Rheumatology

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“…Levels of antiC1q antibodies are a noninvasive biological marker of LN activity. Its sensitivity and specificity is higher for disease activity monitoring than traditional markers, such as C3/C4 consumption or anti-dsDNA (Li, 2013). Laboratory findings in urine express the degree of renal impairment.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of anti-C1q antibodies in SLE

Stiborová¹,

Král²,

Rovenský³

et al. 2015

Acta Facultatis Pharmaceuticae Universitatis Comenianae

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Lupus nephritis (LN) is a severe and frequent complication of systemic lupus erythematosus (SLE). Untreated cases very often lead to patients' death; therefore, it is important to use markers sensitive and specific enough for the diagnosis and subsequent monitoring of nephritis. Autoantibodies against double-stranded DNA (anti-dsDNA) are believed to play a major role in SLE in general and so their significance in prediction and monitoring of glomerular inflammation is low. For prediction of renal flares and effective, well-timed therapy, it is required to have an appropriate marker available. In our study, we have tested sera of 85 SLE patients with or without LN. The criterion for LN determination was the degree of proteinuria (persistent proteinuria > 0.5 g/day, according to ACR criteria for LN). Disease activity was described by SLE disease index (SLEDAI) score, renal functions were stated according to British Isles Lupus Assessment Group score. There were anti-C1q, total anti-dsDNA and high-avidity anti-dsDNA detected in the patients' sera. We did not find any significant difference in average SLEDAI value between patients with renal and non-renal organ complications. Positivity of anti-C1q was more frequent in patients with nephritis than in those without any history of renal disease (58.3 vs. 39.1%). Higher prevalence of these antibodies was evident in patients with clinically active LN than in those without renal improvement (73.1 vs. 39.1%). When comparing anti-C1q with antibodies against structures of DNA, significant differences were found in case of high avidity anti-dsDNA. Our results have confirmed the studies showing that anti-C1q antibodies could serve as a reliable serological marker of LN activity along with other laboratory tests. Detection of anti-C1q together with high avidity anti-dsDNA antibodies seems to be a good algorithm for the prediction of possible renal flares in SLE patients.Lupus nefrititída (LN) je závažnou a častou komplikáciou systémového lupus erythematosus (SLE). Neliečené prípady veľmi často vedú k úmrtiu pacienta, a preto je dôležité používať citlivé a dostatočne špecifické metódy na diagnostiku a sledovanie priebehu nefritídy. Autoprotilátky proti dvojzávitnicovej DNA (anti-dsDNA) hrajú významnú úlohu pri SLE, ale ich význam v predikcii a monitorovaní LN je malý. Preto sa hľadajú špecifickejšie paramatre na predikcie renálnych vzplanutí a sledovanie účinnej a včasnej terapie. V našej štúdii sme testovali séra od 85 SLE pacientov s alebo bez LN. Kritériom pre zaradenie do skupín podľa obličkového postihnutia bol stupeň proteinúrie (pretrvávajúca proteinúria> 0,5 g / deň, podľa kritérií ACR pre LN). Aktivita ochorenia bola popísaná SLEDAI skórom a stupeň obličkového poškodenia podľa BILAG skóre. Anti-C1q, celkové anti-dsDNA a vysoko aviditné anti-dsDNA boli detekované v sére pacientov. Medzi pacientami s poškodením obličiek a extrarenálnymi orgánovými komplikácií sme nezistili žiadny významný rozdiel v celkovej aktivite ochorenia podľa SLEDAI. Pozitivita anti-C1q je častejšia...

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“…This finding is consistent with the observation that serum titer of anti-dsDNA can reflect the global lupus disease activity and particularly the LN. Further investigations suggest that both cross-reactivity and charge–charge interactions render anti-dsDNA antibodies binding with cross-reactive antigens and negatively charged molecules other than dsDNAs 82–86. As shown in Table 3, widely distributed molecules on glomerular mesangial cells, epithelial cells, endothelial cells, basement membranes, glomerular matrix, or extracellular proteins are the targets of anti-dsDNA.…”

Section: Anti-dsdna Antibodies Cross-react With Different Autoantigenmentioning

confidence: 98%

“…These intrarenal IC depositions may derive from either circulating preformed or in situ-formed ICs in glomeruli 9. Further investigations have explored that two mechanisms of cytotoxic autoantibodies can cause glomerular damage via charge–charge interaction81–83 and direct binding to cross-reactive glomerular autoantigens to form in situ IC 84–86. On the other hand, the infiltration of both innate immune cells (monocytes/macrophages/dendritic cells and PMNs) and adaptive immune cells (Th1, Th2, and Th17) into glomerular parenchymal tissues indicates cellular autoimmunity occurrence in lupus glomeruli (Table 2).…”

Section: Immunopathological Mechanisms In Lnmentioning

confidence: 99%

Potential serum and urine biomarkers in patients with lupus nephritis and the unsolved problems

Hsieh¹,

Tsai²,

Yu³

2016

OARRR

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Lupus nephritis (LN) is one of the most frequent and serious complications in the patients with systemic lupus erythematosus. Autoimmune-mediated inflammation in both renal glomerular and tubulointerstitial tissues is the major pathological finding of LN. In clinical practice, the elevated anti-dsDNA antibody titer concomitant with reduced complement C3 and C4 levels has become the predictive and disease-activity surrogate biomarkers in LN. However, more and more evidences suggest that autoantibodies other than anti-dsDNA antibodies, such as anti-nucleosome, anti-C1q, anti-C3b, anti-cardiolipin, anti-endothelial cell, anti-ribonuclear proteins, and anti-glomerular matrix (anti-actinin) antibodies, may also involve in LN. Researchers have demonstrated that the circulating preformed and in situ-formed immune complexes as well as the direct cytotoxic effects by those cross-reactive autoantibodies mediated kidney damage. On the other hand, many efforts had been made to find useful urine biomarkers for LN activity via measurement of immune-related mediators, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomic signature, and assessment of mRNA and exosomal-derived microRNA from urine sediment cell. Our group had also devoted to this field with some novel findings. In this review, we briefly discuss the possible mechanisms of LN and try to figure out the potential serum and urine biomarkers in LN. Finally, some of the unsolved problems in this field are discussed.

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Biomarker Profiling for Lupus Nephritis

Cited by 44 publications

References 78 publications

Identification of Stage‐Specific Genes Associated With Lupus Nephritis and Response to Remission Induction in (NZB × NZW)F1 and NZM2410 Mice

Identification of Stage‐Specific Genes Associated With Lupus Nephritis and Response to Remission Induction in (NZB × NZW)F1 and NZM2410 Mice

Clinical significance of anti-C1q antibodies in SLE

Potential serum and urine biomarkers in patients with lupus nephritis and the unsolved problems

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