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. 2018 Aug 3;12(2):232-238.
doi: 10.1093/ckj/sfy068. eCollection 2019 Apr.

Higher serum galactose-deficient immunoglobulin A1 concentration is associated with stronger mesangial cellular inflammatory response and more severe histologic findings in immunoglobulin A nephropathy

Celine Nguyen  1 , Katrin König  2 , Frederick W K Tam  3 , Helmut Hopfer  4 , Karen Molyneux  5 , Francoise-Isabelle Binet  6 , Min Jeong Kim  1   6
Affiliations

Higher serum galactose-deficient immunoglobulin A1 concentration is associated with stronger mesangial cellular inflammatory response and more severe histologic findings in immunoglobulin A nephropathy

Celine Nguyen et al. Clin Kidney J. .

Abstract

Background: Galactose-deficient immunoglobulin A1 (Gd-IgA1) is known to play a key role in the pathogenesis of IgA nephropathy (IgAN). We aimed to evaluate whether serum Gd-IgA1 is associated with in vitro activation of mesangial cells in individual patients and how this affects the clinical and histologic parameters.

Methods: Serum samples and clinical and histologic data were collected in the University Hospital Basel and Hammersmith Hospital, London. Serum levels of IgA1 and Gd-IgA1 were measured by enzyme-linked immunosorbent assay (ELISA) and lectin-binding assay using lectin Helix aspersa (HA). Primary human mesangial cells were stimulated with IgA1 isolated from serum from individual patients and the concentrations of monocyte chemoattractant protein-1 and interleukin-6 were measured in cell culture supernatant by ELISA.

Results: Thirty-three patients were enrolled. A significant correlation was observed between serum Gd-IgA1 levels and the concentration of MCP-1 in the culture supernatant in individual patients (Spearman r = 0.5969, P = 0.0002). There was no significant correlation between serum Gd-IgA1 levels and proteinuria or estimated glomerular filtration rate at diagnosis. However, the serum Gd-IgA1 level was significantly higher in patients with segmental glomerulosclerosis (S0 versus S1, P = 0.0245) and tubular atrophy/interstitial fibrosis (T0 versus T1 and T2, P = 0.0336; T0 versus T2, P = 0.0225).

Conclusions: Higher serum Gd-IgA1 concentration is associated with stronger mesangial cell inflammatory response with production of a greater amount of MCP-1 in vitro. This in turn is associated with severe histologic changes. The disease progression with worse renal outcome in patients with higher serum Gd-IgA1 may be therefore mediated by more pronounced mesangial cell inflammatory response leading to more severe histologic changes.

Keywords: Gd-IgA1; IgA nephropathy; MCP-1; Oxford classification MEST; mesangial cellular inflammatory response.

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Figures

FIGURE 1
FIGURE 1
Correlation of Gd-IgA1 values from two independent measurements.
FIGURE 2
FIGURE 2
Correlation of serum Gd-IgA1 with (a) MCP-1 and (b) IL-6 from HMCs treated with IgA1 isolates from patients.
FIGURE 3
FIGURE 3
Correlation of serum Gd-IgA1 with proteinuria: (a) PCR and (b) eGFR at the time of diagnosis.
FIGURE 4
FIGURE 4
Serum Gd-IgA1 concentration according to Oxford classification MEST score, (a) M, (b) E, (c) S and (d) T.
FIGURE 5
FIGURE 5
MCP-1 concentration in cell culture supernatant according to Oxford classification MEST score: (a) M, (b) E, (c) S and (d) T.
See this image and copyright information in PMC

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