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Lupus nephritis: an overview of recent findings.

ABSTRACT: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. In susceptible individuals suffering of SLE, in situ formation and deposit of immune complexes (ICs) from apoptotic bodies occur in the kidneys as a result of an amplified epitope immunological response. IC glomerular deposits generate release of proinflammatory cytokines and cell adhesion molecules causing inflammation. This leads to monocytes and polymorphonuclear cells chemotaxis. Subsequent release of proteases generates endothelial injury and mesangial proliferation. Presence of ICs promotes adaptive immune response and causes dendritic cells to release type I interferon. This induces maturation and activation of infiltrating T cells, and amplification of Th2, Th1 and Th17 lymphocytes. Each of them, amplify B cells and activates macrophages to release more proinflammatory molecules, generating effector cells that cannot be modulated promoting kidney epithelial proliferation and fibrosis. Herein immunopathological findings of LN are reviewed.

SUBMITTER: de Zubiria Salgado A

PROVIDER: S-EPMC3318208 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Lupus nephritis: an overview of recent findings.

de Zubiria Salgado Alberto A Herrera-Diaz Catalina C

Autoimmune diseases 20120322

Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE) since it is the major predictor of poor prognosis. In susceptible individuals suffering of SLE, in situ formation and deposit of immune complexes (ICs) from apoptotic bodies occur in the kidneys as a result of an amplified epitope immunological response. IC glomerular deposits generate release of proinflammatory cytokines and cell adhesion molecules causing inflammation. This leads to monocytes an ...[more]

PMID: 22536486

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Project description:BACKGROUND AND OBJECTIVES:In 2012, the Systemic Lupus International Collaborating Clinics proposed that lupus nephritis, in the presence of positive ANA or anti-dsDNA antibody, is sufficient to diagnose SLE. However, this "stand-alone" kidney biopsy criterion is problematic because the ISN/RPS classification does not specifically define lupus nephritis. We investigated the combination of pathologic features with optimal sensitivity and specificity for the diagnosis of lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Three hundred consecutive biopsies with lupus nephritis and 560 contemporaneous biopsies with nonlupus glomerulopathies were compared. Lupus nephritis was diagnosed if there was a clinical diagnosis of SLE and kidney biopsy revealed findings compatible with lupus nephritis. The control group consisted of consecutives biopsies showing diverse glomerulopathies from patients without SLE, including IgA nephropathy, membranous glomerulopathy, pauci-immune glomerulonephritis, membranoproliferative glomerulonephritis (excluding C3 GN), and infection-related glomerulonephritis. Sensitivity and specificity of individual pathologic features and combinations of features were computed. RESULTS:Five characteristic features of lupus nephritis were identified: "full-house" staining by immunofluorescence, intense C1q staining, extraglomerular deposits, combined subendothelial and subepithelial deposits, and endothelial tubuloreticular inclusions, each with sensitivity ranging from 0.68 to 0.80 and specificity from 0.8 to 0.96. The presence of at least two, three, or four of the five criteria had a sensitivity of 0.92, 0.8, and 0.66 for the diagnosis of lupus nephritis, and a specificity of 0.89, 0.95, and 0.98. CONCLUSIONS:In conclusion, combinations of pathologic features can distinguish lupus nephritis from nonlupus glomerulopathies with high specificity and varying sensitivity. Even with stringent criteria, however, rare examples of nonlupus glomerulopathies may exhibit characteristic features of lupus nephritis.

Project description:IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan inflammatory involvement and a mortality rate that is 2.6-fold higher than individuals of the same age and sex in the general population. Approximately 50% of patients with SLE develop renal impairment (lupus nephritis). Delayed diagnosis of lupus nephritis is associated with a higher risk of progression to end-stage renal disease, the need for replacement therapy, and mortality. The initial clinical manifestations of lupus nephritis are often discrete or absent and are usually detected through complementary tests. Although widely used in clinical practice, their accuracy is limited. A great scientific effort has been exerted towards searching for new, more sensitive, and specific biomarkers in recent years. Some systematic reviews have individually evaluated new serum and urinary biomarkers tested in patients with lupus nephritis. This overview aimed to summarize systematic reviews on the accuracy of novel serum and urinary biomarkers for diagnosing lupus nephritis in patients with SLE, discussing how our results can guide the clinical management of the disease and the direction of research in this area.MethodsThe research question is "What is the accuracy of the new serum and urinary biomarkers studied for the diagnosis of LN in patients with SLE?". We searched for systematic reviews of observational studies evaluating the diagnostic accuracy of new serum or urinary biomarkers of lupus nephritis. The following databases were included: PubMed, EMBASE, BIREME/LILACS, Scopus, Web of Science, and Cochrane, including gray literature found via Google Scholar and PROQUEST. Two authors assessed the reviews for inclusion, data extraction, and assessment of the risk of bias (ROBIS tool).ResultsTen SRs on the diagnostic accuracy of new serum and urinary BMs in LN were selected. The SRs evaluated 7 distinct BMs: (a) antibodies (anti-Sm, anti-RNP, and anti-C1q), (b) cytokines (TWEAK and MCP-1), (c) a chemokine (IP-10), and (d) an acute phase glycoprotein (NGAL), in a total of 20 review arms (9 that analyzed serum BMs, and 12 that analyzed BMs in urine). The population evaluated in the primary studies was predominantly adults. Two SRs included strictly adults, 5 reviews also included studies in the paediatric population, and 4 did not report the age groups. The results of the evaluation with the ROBIS tool showed that most of the reviews had a low overall risk of bias.ConclusionsThere are 10 SRs of evidence relating to the diagnostic accuracy of serum and urinary biomarkers for lupus nephritis. Among the BMs evaluated, anti-C1q, urinary MCP-1, TWEAK, and NGAL stood out, highlighting the need for additional research, especially on LN diagnostic panels, and attempting to address methodological issues within diagnostic accuracy research. This would allow for a better understanding of their usefulness and possibly validate their clinical use in the future.RegistrationThis project is registered on the International Prospective Registry of Systematic Reviews (PROSPERO) database (CRD42020196693).

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Lupus nephritis: an overview of recent findings.

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Lupus nephritis: an overview of recent findings.

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