The utility of glomerular C4d immunostaining in renal biopsies in patients with immunoglobulin A nephropathy. A clinicopathological study

Wągrowska-Danilewicz, Małgorzata; Danilewicz, Marian

doi:10.5114/pjp.2017.69691

Cited by 9 publications

(13 citation statements)

References 15 publications

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“…MBL deposits, found in about 25–35% of patients, have been associated with higher proteinuria, lower eGFR, and more severe histopathological lesions (70, 75). Several retrospective studies have confirmed the deleterious prognostic impact of mesangial C4d deposition on renal survival (71, 76, 77). In those series, the prevalence of C4d positivity ranged from 21% in the pediatric cohort up to 38% in the adult Spanish cohort (71, 76, 77).…”

Section: Complement Proteins and Complement Fragments In Pathologymentioning

confidence: 91%

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

et al. 2019

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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.

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Section: Complement Proteins and Complement Fragments In Pathologymentioning

confidence: 91%

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

et al. 2019

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“…The formation of immune complexes could activate the complement system which is composed of classic, alternative and lectin pathways. The activation of complement system in IgAN were initially demonstrated by the presence of complement component C3, C4d, and C5-9 in glomeruli in IgAN patients (8)(9)(10). In recent years, researchers started to explore which complement pathway mediates the Gd-IgA 1 /anti-glycan immune complex induced glomerular damage in IgAN patients.…”

Section: Introductionmentioning

confidence: 99%

Alternative Complement Pathway Is Activated and Associated with Galactose-Deficient IgA1 Antibody in IgA Nephropathy Patients

et al. 2021

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BackgroundGalactose-deficient IgA1 (Gd-IgA1) and alternative complement pathway activation are considered to be involved in the pathogenesis of IgA nephropathy (IgAN). Nevertheless, the relationships between alternative pathway activation and disease activity or Gd-IgA1 level remains unclear.MethodsNinety-eight biopsy-diagnosed IgAN, twenty-five primary focal segmental sclerosis (FSGS) patients and forty-two healthy individuals were recruited in this study. Among them, fifty IgAN patients received immunosuppression. Follow-up blood samples at 1 and 3~6 months after immunosuppression were collected. Plasma levels of complement C5a, factor Ba and Gd-IgA1 were measured and analyzed. Immunostaining for complement was performed in twenty-five IgAN and FSGS patients.ResultsAt baseline, IgAN patients had higher levels of plasma C5a, factor Ba and Gd-IgA1 than control subjects. Gd-IgA1 levels positively correlated with plasma C5a and factor Ba. In addition, levels of factor Ba and Gd-IgA1 were positively associated with proteinuria and negatively associated with renal function. Immunostaining revealed positive staining for factor Bb and C3c in glomeruli in IgAN patients, but not in FSGS patients. At baseline, patients receiving immunosuppression had more severe proteinuria and higher factor Ba. After 6 months, eGFR declined and proteinuria persisted in patients without immunosuppression. In contrast, patients who received immunosuppression exhibited decreased plasma levels of C5a, factor Ba, and Gd-IgA1 as early as 1 month after treatment. Proteinuria decreased and renal function also remained stable 6 months after immunosuppression.ConclusionsOur results indicate a close relationship between alternative complement pathway activation, Gd-IgA1 concentration and clinical severity of IgAN. Level of complement factor B may be a potential marker for disease activity and therapeutic target in IgAN patients.

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“…IF is more sensitive for the demonstration of capillary staining (i.e., peritubular capillaries), 6 but a side-by-side comparison of the 2 methods showed no significant difference for glomerular staining 3, 7. Both methods have been successfully used in native kidney samples 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19…”

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confidence: 99%

Epidemiology and Pathophysiology of Glomerular C4d Staining in Native Kidney Biopsies

Drachenberg

Chandra

Haririan

et al. 2019

Kidney International Reports

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IntroductionRoutine C4d staining in renal transplantation has stimulated its use in kidney biopsies with glomerulonephritis (GN). Methodical description on staining patterns in the native kidney is not available.MethodsWe retrospectively evaluated C4d staining in formalin-fixed paraffin-embedded sections from 519 native kidney biopsies (bx) with and without glomerular disease.ResultsStrong C4d staining was consistently present in immune-complex GN, including lupus nephritis (LN) (n = 68), membranous GN (n = 24), membranoproliferative glomerulonephritis (MPGN) pattern (n = 22), fibrillary GN (n = 3), and proliferative GN with monoclonal IgG (n = 3). C4d stained all cases of postinfectious GN (n = 7) amyloidosis (n = 20) and C1q GN (n = 3). In contrast, IgA nephropathy (IgAN) (n = 34), was negative in 62% of bx, with the rest staining variably. The E1 Oxford classification score correlated with capillary wall C4d staining (P = 0.05). C4d marked the glomerular and arteriolar lesions in thrombotic microangiopathy (TMA; n = 16), the glomerular sclerotic segments in focal segmental glomerulosclerosis (FSGS; n = 77), and marked areas of necrosis in crescentic GN (n = 21). In diabetic glomerulopathy (n = 70), C4d marked advanced insudative lesions but was negative otherwise. C4d weakly stained the mesangium, or was negative in normal biopsies (n = 13), minimal change disease (MCD; n = 21), thin basement membrane disease (n = 20), Alport (n = 3), IgM nephropathy (n = 2), C3 glomerulopathy (n = 5), acute interstitial nephritis (n = 12), acute tubular necrosis (n = 22), ischemic glomerulopathy/nephrosclerosis (n = 23), and other miscellaneous processes (n = 14). Staining in tubular basement membranes and peritubular capillaries was most common in lupus.ConclusionBased on reliable staining in lupus and membranous GN, C4d staining is potentially useful as a screening and diagnostic tool, if only paraffin-embedded tissue is available. Knowledge of C4d staining patterns in normal and pathological tissues enhances its diagnostic value.

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The utility of glomerular C4d immunostaining in renal biopsies in patients with immunoglobulin A nephropathy. A clinicopathological study

Cited by 9 publications

References 15 publications

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

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

Alternative Complement Pathway Is Activated and Associated with Galactose-Deficient IgA1 Antibody in IgA Nephropathy Patients

Epidemiology and Pathophysiology of Glomerular C4d Staining in Native Kidney Biopsies

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