The Reproducibility of Semiquantitative Analyses of Renal Histology

Pirani, C L; Pollak, Victor E.; Schwartz, Franklin D.

doi:10.1159/000179336

Cited by 99 publications

(33 citation statements)

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“…The concept of active and chronic renal lesions was first introduced by Pirani, Pollak, and Schwartz (17) and subsequently refined by Morel-Maroger et al (18). Austin et al (19) devised a system of applying semiquantitative scores for activity and chronicity by grading and adding the individual Membranous glomerulonephritis morphologic components in a given biopsy as a guide to treatment and prognosis.…”

Section: Classification Of Lupus Nephritis: Historymentioning

confidence: 99%

The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited

Weening

D’Agati²,

Schwartz³

et al. 2004

Journal of the American Society of Nephrology

1,778

1,115

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Abstract. The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving Ͻ50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving Ն50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.The morphologic changes in a renal biopsy from a patient with systemic lupus erythematosus (SLE) comprise a spectrum of vascular, glomerular, and tubulointerstitial lesions. The classification of SLE nephritis has evolved over the past 40 years as more lesions were identified and defined. It has been an increasing challenge to apply new pathogenetic insights to the interpretation of the renal biopsy in SLE and to correlate pathologic findings with clinical symptoms, choice of treatment, and prognosis. The current classification, which was advanced in 1982 (1) and revised in 1995 (2), reflects our understanding of the pathogenesis of the various forms of renal injury in SLE nephritis. However, subsequent clinicopathologic studies have revealed the need for clarification of the different categories and the diagnostic terminology. The clas-

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Section: Classification Of Lupus Nephritis: Historymentioning

confidence: 99%

The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited

Weening

D’Agati²,

Schwartz³

et al. 2004

Journal of the American Society of Nephrology

1,778

1,115

View full text Add to dashboard Cite

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“…At least 10 glomeruli were examined for each animal. An overall grade was applied that reflects all of the changes and takes into account the proportion of the appropriate structures affected in the entire section (42,43).…”

Section: Methodsmentioning

confidence: 99%

A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaamice

Bubier

Sproule

Foreman

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

269

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Interleukin 21 (IL-21) is a pleiotropic cytokine produced by CD4 T cells that affects the differentiation and function of T, B, and NK cells by binding to a receptor consisting of the common cytokine receptor ␥ chain and the IL-21 receptor (IL-21R). IL-21, a product associated with IL-17-producing CD4 T cells (T H17) and follicular CD4 T helper cells (T FH), has been implicated in autoimmune disorders including the severe systemic lupus erythematosus (SLE)-like disease characteristic of BXSB-Yaa mice. To determine whether IL-21 plays a significant role in this disease, we compared IL-21R-deficient and -competent BXSB-Yaa mice for multiple parameters of SLE. The deficient mice showed none of the abnormalities characteristic of SLE in IL-21R-competent Yaa mice, including hypergammaglobulinemia, autoantibody production, reduced frequencies of marginal zone B cells and monocytosis, renal disease, and premature morbidity. IL-21 production associated with this autoimmune disease was not a product of T H17 cells and was not limited to conventional CXCR5 ؉ TFH but instead was produced broadly by ICOS ؉ CD4 ؉ splenic T cells. IL-21 arising from an abnormal population of CD4 T cells is thus central to the development of this lethal disease, and, more generally, could play an important role in human SLE and related autoimmune disorders.autoimmune disease ͉ autoantibodies ͉ B cells ͉ T cells S ystemic lupus erythematosus (SLE) in humans is a chronic, multigenic autoimmune disease characterized by a wide spectrum of clinical abnormalities, the production of multiple autoantibodies, and the generation of immune complexes that often lead to severe renal disease. The production of autoantibodies is indicative of a profound breakdown in humoral tolerance mechanisms and B cell hyperactivity caused either by B cell-intrinsic abnormalities or immunoregulatory defects of other cell types. Mouse models genetically programmed to develop characteristics of SLE have proven useful for characterizing this disease process and for identifying potential therapeutic targets. Among the most interesting models of SLE are the BXSB mice bearing the Y chromosome-linked autoimmune acceleration (Yaa) mutation (1). Affected animals develop a remarkably severe disease characterized by lymphoid hyperplasia, monocytosis, hypergammaglobulinemia, and severe immune complex-mediated glomerulonephritis. In contrast to the female prevalence of SLE in humans, this disease is male-biased because of the epistatic effects of BXSB-background autosomal alleles in combination with Yaa. This mutant locus is the result of the duplication of at least 17 genes in the X chromosome, including Toll-like receptor 7 (Tlr7), and their placement in the Y chromosome (2, 3). Remarkably, severe autoimmune disease results from the presence of an extra copy of these X-chromosome genes in Yaa mice in combination with BXSB-background autosomal alleles.IL-21 is a pleiotropic member of the ␥-chain family of cytokines, which engages the IL-21 receptor (IL-21R) and the common cytokine re...

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“…(total score 24) [23,24]. For the activity index, we calculated histological features such as cell proliferation, fibrinoid necrosis/ karyorrhexis, cellular crescent formation, hyaline thrombi, wire loops, leucocyte infiltration in glomeruli and mononuclear cell infiltration in tubulointerstitium based on renal biopsy.…”

Section: Determination Of Light Microscopic Findingsmentioning

confidence: 99%

Imbalance between interleukin-6 and adrenomedullin mRNA levels in peripheral blood mononuclear cells of patients with lupus nephritis

Nishitani

Kubo

Iwano

et al. 2001

Clinical and Experimental Immunology

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SUMMARYIn this study, we measured the mRNA levels of adrenomedullin (AM), C-type natriuretic peptide, vascular endothelial growth factor, interleukin-1b (IL-1b ) and interleukin-6 (IL-6) in peripheral blood mononuclear cells (PBMC) of 34 patients with lupus nephritis (LN) (15 active and 19 inactive) and 30 healthy volunteers. mRNA levels were measured using a real-time quantitative PCR method. Compared with healthy volunteers, IL-6 mRNA levels were elevated in LN patients (P , 0´005), while AM mRNA levels were decreased (P , 0´05). Also, IL-6 mRNA levels were higher and AM mRNA levels lower in active LN patients compared with inactive LN patients. In addition, IL-6 mRNA levels positively correlated and AM mRNA levels negatively correlated with SLE disease activity index and laboratory findings, such as blood urea nitrogen, serum creatinine, 50% haemolytic unit of complement and urinary excretion of protein over 24 h. Furthermore, IL-6 mRNA levels were negatively correlated with AM mRNA levels within the same LN patients. With regard to pathological findings, our results showed that IL-6 mRNA levels were higher, and AM mRNA levels significantly lower in patients with a high activity index compared to those with a low activity index. Following treatment with prednisolone, IL-6 mRNA levels in active LN patients decreased and AM mRNA levels increased to levels comparable to those in inactive LN and healthy volunteers. In vitro studies further demonstrated that elevated IL-6 mRNA levels in active LN patient PBMC were suppressed by the addition of adrenomedullin. Our results suggest that an imbalance between IL-6 and AM levels may play an important role in the progression of SLE, and that the mRNA levels of these genes in PBMC may be used as a disease activity index for SLE.

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The Reproducibility of Semiquantitative Analyses of Renal Histology

Cited by 99 publications

References 1 publication

The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited

The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited

A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaamice

Imbalance between interleukin-6 and adrenomedullin mRNA levels in peripheral blood mononuclear cells of patients with lupus nephritis

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