Value of biomarkers for predicting immunoglobulin A vasculitis nephritis outcome in an adult prospective cohort

Berthelot, Laureline; Jamin, Agnès; Viglietti, Denis; Chemouny, Jonathan; Ayari, H.; Michelet, Pierre; Housset, P; Sauvaget, Virginia; Hurtado-Nédelec, Margarita; Vrtovsnik, François; Daugas, Éric; Amoura, Zahir; Audard, Vincent; Azib, Sonia; Bagot, M.; Baudouin, Véronique; Benveniste, Olivier; Bézier, M.; Bloch-Queyrat, Coralie; Bocquet, N.; Boffa, Jean‐Jacques; Bouaziz, Jean‐David; Bouchireb, Karim; Bourrat, E.; Bouvier, Philippe; Brochard, Karine; Burda, Guillaume; Bussone, Guillaume; Caudwell, Valérie; Champion, L.; Chéron, G.; Cordoliani, F.; Decramer, Stéphane; Dehen, L.; Dehoux, Laurène; Delahousse, Michel; Deschênes, Georges; Menthon, Mathilde de; Demongeot, C.; Dossier, Antoine; Dossier, Claire; Dehoux, Monique; Fain, Olivier; Farge, D.; Fila, Marc; Fite, C.; Flamant, Martin; Flament, Héloïse; Froissart, Antoine; Funck‐Brentano, Elisa; Georgin‐Lavialle, Sophie; Glotz, Denis; Godeau, Bertrand; Grimbert, Philippe; Guillevin, Loı̈c; Halabi-Tawil, M.; Halphen, Isabelle; Karras, Alexandre; Kwon, Thérèsa; Lebas, C.; Limal, Nicolas; Maisin, Anne; Mathian, Alexis; Mékinian, A.; Mercier, J; Mihout, Fabrice; Monsel, Gentiane; Pestre, Vincent; Piram, Maryam; Quéméneur, T.; Raimbourg, Quentin; Raynaud-Simon, A.; Rémy, Philippe; Rivet, Jacqueline; Robert, Alain; Salomon, Rémi; Saussine-Hickman, Anne; Seidowsky, Alexandre; Smail, A.; Tellier, Stéphanie; Thervet, Éric; Tricot, L.; Vanhille, Philippe; Verhelst, David; Vrigneaud, Laurence; Verhoeven, Anne-Sophie; Verine, Jérôme; Vidal‐Petiot, Emmanuelle; Viguier, Manuelle; Vittoz, Nathalie; Monteiro, Renato C.; Pillebout, Évangéline

doi:10.1093/ndt/gfx300

Cited by 35 publications

(45 citation statements)

References 27 publications

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“…However, to our knowledge, comparisons of serum inflammatory cytokines between patients with HSPN or IgAN are limited. In the present study, serum inflammatory cytokines were higher in patients with HSPN with systemic symptoms, which is consistent with previous reports [2,17,46]. Furthermore, elevated serum inflammatory cytokines, especially IL-8 and MCP-1, tended to be associated with intensity of g-Gd-IgA1 deposition and degree of active lesions such as endothelial injury or crescent formation in patients with HSPN.…”

Section: Plos Onesupporting

confidence: 92%

“…In other words, elevation of serum inflammatory cytokines was evident in patients with HSPN, regardless of the anti-inflammatory effects of ST. Thus far, levels for serum inflammatory cytokines were mainly compared among patients with HSP with skin lesions alone and patients with HSP with systemic symptoms [2,17,46]. However, to our knowledge, comparisons of serum inflammatory cytokines between patients with HSPN or IgAN are limited.…”

Section: Plos Onementioning

confidence: 99%

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A cross-sectional analysis of clinicopathologic similarities and differences between Henoch-Schönlein purpura nephritis and IgA nephropathy

et al. 2020

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Introduction Recent studies noted that Henoch-Schö nlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) share the feature of galactose-deficient IgA1 (Gd-IgA1)-oriented pathogenesis, although there are distinct clinical differences. We aimed to clarify the clinicopathologic differences between these 2 diseases. Methods We cross-sectionally analyzed adult patients with HSPN (n = 24) or IgAN (n = 56) who underwent renal biopsy (RB) between 2008 and 2018 at Showa University Hospital. Serum Gd-IgA1 (s-Gd-IgA1) levels at the time of RB were compared among study groups using enzyme-linked immunosorbent assay (ELISA) with anti-human Gd-IgA1-specific monoclonal antibody (KM55). We also immunohistochemically stained paraffin-embedded sections for glomerular Gd-IgA1 (g-Gd-IgA1)-deposition using KM55. Serum inflammatory cytokines were measured using ELISA. Results Glomerular endothelial injury with subendothelial IgA deposition was significant in patients with HSPN. Serum IL-8, MCP-1, TNF-α, and IL-6 levels were significantly higher in patients with HSPN than IgAN. Levels of s-Gd-IgA1 were comparable among patients with HSPN and IgAN, and a similar degree of g-Gd-IgA1-deposition was detected in both diseases. Furthermore, g-Gd-IgA1-deposition was evident in patients with histopathologically advanced HSPN or IgAN. In HSPN, significant positive correlations between s-Gd-IgA1 levels and crescent formation or IL-6 elevation were confirmed, and g-Gd-IgA1 intensity showed a significant positive correlation with MCP-1 and a tendency to positively correlate with IL-8. Meanwhile, patients with IgAN showed no correlation between inflammatory cytokines and both-Gd-IgA1. Moreover, most g-Gd-IgA1-positive areas were not double stained with CD31 in HSPN.

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Section: Plos Onesupporting

confidence: 92%

Section: Plos Onementioning

confidence: 99%

A cross-sectional analysis of clinicopathologic similarities and differences between Henoch-Schönlein purpura nephritis and IgA nephropathy

et al. 2020

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“…We report serum GD-IgA1 levels in precisely phenotyped IgAV patients with systemic and skin-limited IgAV using a specific monoclonal antibody (KM55) based ELISA. Previous studies in adult and pediatric IgAV that have reported serum GD-IgA1 levels have used a lectin-based assay which is known to vary between laboratories [12,16,17]. In one study in children with IgAV with and without nephritis no significant difference in the median serum GD-IgA1 levels was seen at the onset of IgAV [18], while Berthelot et al found i) higher serum levels of GD-IgA1 in 60 adult patients with IgAVN when compared with 25 patients with skin-limited IgAV (they did not explicitly use this term and definition), and ii) slightly, but not significantly increased serum levels in skin-limited IgAV compared to healthy subjects (as in our study) [12].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Previous studies in adult and pediatric IgAV that have reported serum GD-IgA1 levels have used a lectin-based assay which is known to vary between laboratories [12,16,17]. In one study in children with IgAV with and without nephritis no significant difference in the median serum GD-IgA1 levels was seen at the onset of IgAV [18], while Berthelot et al found i) higher serum levels of GD-IgA1 in 60 adult patients with IgAVN when compared with 25 patients with skin-limited IgAV (they did not explicitly use this term and definition), and ii) slightly, but not significantly increased serum levels in skin-limited IgAV compared to healthy subjects (as in our study) [12]. Similarly, two other studies reported that IgA1 from 24 and 33 children with renal involvement showed significantly higher lectin binding (indicating high GD-IgA1 levels) than IgA1 from 22 and 17 children lacking renal involvement [16,17], while lectin binding of IgA1 from children with IgAV without renal involvement did not differ from healthy subjects [16].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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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

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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.

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IgA vasculitis

Pillebout

Sunderkötter

2021

Semin Immunopathol

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Value of biomarkers for predicting immunoglobulin A vasculitis nephritis outcome in an adult prospective cohort

Abstract: Taken together, these results showed that serum Gd-IgA1 and urinary IgA, IgG, IgM, NGAL, IL-1β, IL-6, IL-8, IL-10, IgA-IgG and IgA-sCD89 complexes were associated with nephritis in IgAV patients. Urinary IgA level may improve patient risk stratification for poor outcome.

Cited by 35 publications

References 27 publications

A cross-sectional analysis of clinicopathologic similarities and differences between Henoch-Schönlein purpura nephritis and IgA nephropathy

A cross-sectional analysis of clinicopathologic similarities and differences between Henoch-Schönlein purpura nephritis and IgA nephropathy

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

IgA vasculitis

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