Comprehensive evaluation of the significance of immunofluorescent findings on clinicopathological features in IgA nephropathy

Katafuchi, Ritsuko; Nagae, Hiroshi; Masutani, Kosuke; Tsuruya, Kazuhiko; Matsumoto, Koji

doi:10.1007/s10157-018-1619-6

Cited by 36 publications

(26 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[22][23][24] We checked the impact of glomerular C3 deposition on IgAN in recent years, and our findings are shown in Table S1. [25][26][27][28][29][30][31] In this study, we also found that patients with intense glomerular C3 deposition also had glomerular IgA, IgM, and IgG deposition. This suggests that the complement alternative pathway is associated with immune complex deposition in the glomerulus.…”

Section: Discussionsupporting

confidence: 75%

“…Many studies have previously shown that glomerular C3 deposition and complement activation are involved in the pathogenesis of patients with various kidney diseases, including lupus nephritis, 19 C3 glomerulopathy, 20 antineutrophil cytoplasmic antibody‐mediated crescentic glomerulonephritis, 21 and IgAN 22–24 . We checked the impact of glomerular C3 deposition on IgAN in recent years, and our findings are shown in Table 25–31 . In this study, we also found that patients with intense glomerular C3 deposition also had glomerular IgA, IgM, and IgG deposition.…”

Section: Discussionsupporting

confidence: 66%

See 1 more Smart Citation

Severe glomerular C3 deposition indicates severe renal lesions and a poor prognosis in patients with immunoglobulin A nephropathy

Wang

et al. 2021

Histopathology

View full text Add to dashboard Cite

Severe glomerular C3 deposition indicates severe renal lesions and a poor prognosis in patients with immunoglobulin A nephropathy Aims: Glomerular complement 3 (C3) deposition is often observed in renal biopsies of patients with IgA nephropathy (IgAN); however, the relationship between the intensity of C3 deposition and the long-term prognosis of IgAN has rarely been reported. In this retrospective study, we aimed to evaluate the prognostic value of glomerular C3 deposition for IgAN progression. Methods and results: From June 2009 to June 2010, a total of 136 adult patients with IgAN were enrolled in the study. According to the intensity of glomerular C3 deposition, patients were divided into a glomerular C3 high group (34 patients) and a glomerular C3 low group (102 patients). The levels of clinical parameters, glomerular immune complexes, histopathological features, and serum cytokines of the two groups were compared. On the basis of an average of 105 months of follow-up, the predictive value of glomerular C3 deposition for IgAN progression was also investigated. Patients in the C3 high group had more severe glomerular IgA, IgG, IgM, and complement factor H deposition, a higher percentage of mesangial hypercellularity (M1), and higher levels of segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T2), and crescents (C2) than those in the C3 low group. Renal biopsies in the C3 high group showed higher densities of interstitial inflammatory cells and higher levels of serum interferon-c than those in the C3 low group. Multivariate Cox regression analysis revealed that a higher intensity of glomerular C3 deposition remained as an independent predictor of serum creatinine doubling and end-stage renal disease. Conclusions: A high intensity of glomerular C3 deposition is associated with the severity of renal lesions, and predicts long-term poor renal survival for IgAN patients.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Discussionsupporting

confidence: 66%

Severe glomerular C3 deposition indicates severe renal lesions and a poor prognosis in patients with immunoglobulin A nephropathy

Wang

et al. 2021

Histopathology

View full text Add to dashboard Cite

show abstract

“…After we have provided evidence that Gd-IgA1 is deposited at vessels of systemic and skin-limited IgAV, we believe it is reasonable to extrapolate the IgAN multi-hit hypothesis [25][26][27][28] to IgAV as shown in Figure 3. We detected co-deposition of IgG (as in IgAN) in 2 cases of skin-limited IgAV consistent with the presence of IgA-IgG immune complexes [29]. In those cases with no IgG codeposition it is likely that these patients developed IgA1 autoantibodies to GD-IgA1 (as has been described in IgAN) which cannot be definitively identified with current staining techniques.…”

Section: Accepted Manuscriptsupporting

confidence: 72%

Galactose-deficient IgA1 in skin and serum from patients with skin-limited and systemic IgA vasculitis

Neufeld

Molyneux

Pappelbaum

et al. 2019

Journal of the American Academy of Dermatology

View full text Add to dashboard Cite

Background: IgA-vasculitis (IgAV) encompasses a systemic form involving kidneys, gut, skin or joints, and a skin-limited form. One characteristic feature of systemic IgAV is deposition of galactosedeficient IgA1 (GD-IgA1) in kidneys (as in IgA-nephropathy). The relevance of GD-IgA1 for cutaneous vasculitis is unknown. Objective: We investigated if GD-IgA1 is deposited perivascularly in systemic and also skin-limited IgAV, and if its serum levels differ between both forms. Methods: In a case control study, deposition of GD-IgA1 was analysed immunohistochemically by KM55-antibody in skin biopsies from 12 patients with skin-limited and 4 with systemic IgAV. GD-IgA1levels were compared by ELISA in sera from 15 patients each with skin-limited and systemic IgAV and from 11 healthy subjects. Results: All biopsies from systemic, but also from skin-limited IgAV revealed perivascular GD-IgA1deposition. The average GD-IgA1-level in serum was significantly higher in systemic than in skinlimited IgAV, despite overlap between both groups. Limitations: Although high GD-IgA1-levels may be predictive of systemic IgAV, patient numbers were too low to determine cutoff values for systemic versus skin-limited IgAV. Conclusion: While perivascular GD-IgA1-deposition is a prerequisite for systemic and skin-limited IgAV, high GD-IgA1-levels in some patients with systemic IgAV suggest a dose-dependent effect of GD-IgA1 in IgAV.

show abstract

“…Hallmarks of classical pathway activation, such as C1q, are usually not detected in the glomeruli of patients with IgAN (57), although it may be found in biopsies with advanced glomerulosclerosis (72). Therefore, the presence of glomerular C4d in IgAN suggests activation of the lectin pathway rather than the classical pathway.…”

Section: Complement Proteins and Complement Fragments In Pathologymentioning

confidence: 99%

The Emerging Role of Complement Proteins as a Target for Therapy of IgA Nephropathy

et al. 2019

View full text Add to dashboard Cite

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and a common cause of end-stage renal disease. Evaluation of a kidney biopsy is necessary for diagnosis, with routine immunofluorescence microscopy revealing dominant or co-dominant IgA immunodeposits usually with complement C3 and sometimes IgG and/or IgM. IgA nephropathy reduces life expectancy by more than 10 years and leads to kidney failure in 20–40% of patients within 20 years of diagnosis. There is accumulating clinical, genetic, and biochemical evidence that complement plays an important role in the pathogenesis of IgA nephropathy. The presence of C3 differentiates the diagnosis of IgA nephropathy from the subclinical deposition of glomerular IgA. Markers for the activation of the alternative and mannan-binding lectin (MBL) pathways in renal-biopsy specimens are associated with disease activity and portend a worse renal outcome. Complement proteins in the circulation have also been evaluated in IgA nephropathy and found to be of prognostic value. Recently, genetic studies have identified IgA nephropathy-associated loci. Within these loci are genes encoding products involved in complement regulation and interaction with immune complexes. Put together, these data identify the complement cascade as a rational treatment target for this chronic kidney disease. Recent case reports on the successful use of humanized anti-C5 monoclonal antibody eculizumab are consistent with this hypothesis, but a better understanding of the role of complement in IgA nephropathy is needed to guide future therapeutic interventions.

show abstract

Comprehensive evaluation of the significance of immunofluorescent findings on clinicopathological features in IgA nephropathy

Cited by 36 publications

References 33 publications

Severe glomerular C3 deposition indicates severe renal lesions and a poor prognosis in patients with immunoglobulin A nephropathy

Severe glomerular C3 deposition indicates severe renal lesions and a poor prognosis in patients with immunoglobulin A nephropathy

Galactose-deficient IgA1 in skin and serum from patients with skin-limited and systemic IgA vasculitis

The Emerging Role of Complement Proteins as a Target for Therapy of IgA Nephropathy

Contact Info

Product

Resources

About