Clinical relevance of membrane attack complex deposition in children with IgA nephropathy and Henoch-Schönlein purpura

Dumont, Camille; Mérouani, Aïcha; Ducruet, Thiérry; Benoît, Geneviève; Clermont, Marie-Josée; Lapeyraque, Anne Laure; Phan, Véronique; Patey, Natalie

doi:10.1007/s00467-019-04445-x

Cited by 18 publications

(29 citation statements)

References 27 publications

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“…Although the aforementioned studies included children, two studies including only children did not find any correlation between glomerular or tubular staining and histological lesions ( 19 , 97 ).…”

Section: Kidney Diseases Due To Immune Complex Depositionmentioning

confidence: 93%

“…Staining of C5b-9 in the vascular wall is recognized as a positive control ( 19 , 134 ). Staining in the vascular pole of the glomerulus was similarly common ( Figure 2A ).…”

Section: Healthy Kidneysmentioning

confidence: 99%

“…Mostly small descriptive studies found C5b-9 as coarse granules in the glomerulus ( 57 , 58 , 72 , 76 , 81 , 137 , 139 , 143 , 158 , 160 , 161 )—always in the mesangium, sometimes also along the capillary wall ( 19 , 44 , 52 , 67 , 75 , 96 , 97 , 110 , 115 , 124 , 128 , 162 – 166 ), in one case report only along the capillary wall ( 159 ) —, along Bowman’s capsule ( 52 , 162 , 163 ), as coarse granules ( 19 , 44 , 52 , 57 , 70 , 72 , 75 , 96 , 97 , 110 , 115 , 163 ) or linearly ( 110 , 115 ) along the tubular basement membrane and occasionally on tubular cells ( 110 ), and in the vascular wall ( 19 , 52 , 57 , 67 , 72 , 96 , 110 , 115 , 137 , 162 ). Deposits along the capillary wall were localized in the subepithelial space ( 97 , 164 ).…”

Section: Kidney Diseases Due To Immune Complex Depositionmentioning

confidence: 99%

“…The extent of staining in tubules varied widely between 19 and 87% ( 110 , 115 ). Deposits were furthermore present in areas of mesangial expansion and in glomerular and vascular areas of amyloidosis, hyalinosis, and sclerosis ( 19 , 44 , 57 , 67 , 72 , 75 , 96 , 97 , 143 ) but not in crescents ( 19 , 72 , 96 , 97 ). Among patients with IgA nephropathy or IgA vasculitis with nephritis together, deposits were less frequent in the mesangium and vascular wall ( 19 , 167 ).…”

Section: Kidney Diseases Due To Immune Complex Depositionmentioning

confidence: 99%

“…Inhibitors of other complement factors are being developed ( 7 – 9 ). Although eculizumab seems to benefit particularly patients in whom much C5b-9 is formed ( 4 , 11 , 18 , 19 ), it remains uncertain which patients benefit from which complement inhibitor.…”

Section: Introductionmentioning

confidence: 99%

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Deposition of the Membrane Attack Complex in Healthy and Diseased Human Kidneys

et al. 2021

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The membrane attack complex—also known as C5b-9—is the end-product of the classical, lectin, and alternative complement pathways. It is thought to play an important role in the pathogenesis of various kidney diseases by causing cellular injury and tissue inflammation, resulting in sclerosis and fibrosis. These deleterious effects are, consequently, targeted in the development of novel therapies that inhibit the formation of C5b-9, such as eculizumab. To clarify how C5b-9 contributes to kidney disease and to predict which patients benefit from such therapy, knowledge on deposition of C5b-9 in the kidney is essential. Because immunohistochemical staining of C5b-9 has not been routinely conducted and never been compared across studies, we provide a review of studies on deposition of C5b-9 in healthy and diseased human kidneys. We describe techniques to stain deposits and compare the occurrence of deposits in healthy kidneys and in a wide spectrum of kidney diseases, including hypertensive nephropathy, diabetic nephropathy, membranous nephropathy, IgA nephropathy, lupus nephritis, C3 glomerulopathy, and thrombotic microangiopathies such as the atypical hemolytic uremic syndrome, vasculitis, interstitial nephritis, acute tubular necrosis, kidney tumors, and rejection of kidney transplants. We summarize how these deposits are related with other histological lesions and clinical characteristics. We evaluate the prognostic relevance of these deposits in the light of possible treatment with complement inhibitors.

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Section: Kidney Diseases Due To Immune Complex Depositionmentioning

confidence: 93%

“…Staining of C5b-9 in the vascular wall is recognized as a positive control ( 19 , 134 ). Staining in the vascular pole of the glomerulus was similarly common ( Figure 2A ).…”

Section: Healthy Kidneysmentioning

confidence: 99%

Section: Kidney Diseases Due To Immune Complex Depositionmentioning

confidence: 99%

Section: Kidney Diseases Due To Immune Complex Depositionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Deposition of the Membrane Attack Complex in Healthy and Diseased Human Kidneys

et al. 2021

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IgA vasculitis with nephritis: update of pathogenesis with clinical implications

et al. 2021

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Urinary complement proteins are increased in children with IgA vasculitis (Henoch-Schönlein purpura) nephritis

Wright

Marro²,

Northey³

et al. 2022

Pediatr Nephrol

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Background Children with immunoglobulin A vasculitis (IgAV Henoch-Schönlein purpura) frequently encounter nephritis (IgAV-N) with 1–2% risk of kidney failure. The pathophysiology of IgAV-N is not fully understood with speculation that complement may contribute. The aim of this study was to identify whether urinary complement proteins are increased in children with IgAV-N. Methods A cross-sectional prospective cohort of children with IgAV were recruited together with controls including healthy children and children with systemic lupus erythematosus (SLE). Patients were subdivided according to the presence of nephritis. Urinary C3, C4, C5, and C5a were measured by enzyme-linked immunosorbent assay (ELISA) and corrected for urinary creatinine. Results The study included 103 children; 47 with IgAV (37 IgAV without nephritis, IgAVwoN; 10 IgAV-N), 30 SLE and 26 healthy children. Urinary complement C3, C4, and C5 were all statistically significantly increased in all children with IgAV compared to SLE patients (all p < 0.05). In patients with IgAV-N, urinary complement C3, C4, C5, C5a were all statistically significantly increased compared to IgAVwoN (C3 14.65 μg/mmol [2.26–20.21] vs. 2.26 μg/mmol [0.15–3.14], p = 0.007; C4 6.52 μg/mmol [1.30–9.72] vs. 1.37 μg/mmol [0.38–2.43], p = 0.04; C5 1.36 μg/mmol [0.65–2.85] vs. 0.38 μg/mmol [0.03–0.72], p = 0.005; C5a 101.9 ng/mmol [15.36–230.0] vs. 18.33 ng/mmol [4.27–33.30], p = 0.01). Using logistic regression, the urinary complement components produced an outstanding ability to discriminate between patients with and without nephritis in IgAV (AUC 0.92, p < 0.001). Conclusions Children with IgAV-N have evidence of increased complement proteins present in their urine that may indicate a pathological role and may allow treatment stratification. Graphical abstract

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Clinical relevance of membrane attack complex deposition in children with IgA nephropathy and Henoch-Schönlein purpura

Cited by 18 publications

References 27 publications

Deposition of the Membrane Attack Complex in Healthy and Diseased Human Kidneys

Deposition of the Membrane Attack Complex in Healthy and Diseased Human Kidneys

IgA vasculitis with nephritis: update of pathogenesis with clinical implications

Urinary complement proteins are increased in children with IgA vasculitis (Henoch-Schönlein purpura) nephritis

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