Biomarkers of IgA vasculitis nephritis in children

Abstract

Henoch–Schönlein purpura is a systemic vasculitis characterized by IgA deposits, which target the skin, joints, and kidneys, among other organs. In children, prognosis is often good but little is known about biomarkers of pediatric nephritis. We hypothesized that biological markers, including cytokines, immunoglobulins, IgA-immune complexes, IgA glycosylation and neutrophil gelatinase-associated lipocalin (NGAL), may discriminate IgA vasculitis (IgAV) pediatric patients with renal involvement from those without renal involvement. Fifty children at the time of IgAV rash between 2010 and 2015 were prospectively enrolled and compared to 21 controls. All patients were assessed for clinical and biological parameters at the time of diagnosis, including the levels of cytokines, immunoglobulins, immune complexes, IgA glycosylation and NGAL in serum and urine. Among IgAV patients, 33 patients exhibited nephritis (IgAV-N) and 17 children were without nephritis (IgAV-woN). The serum level of galactose-deficient (Gd)-IgA1 (p<0.01) and the urinary concentrations of IgA, IgG, IgM, IL-6, IL-8, IL-10, IgA-IgG complexes and IgA-sCD89 complexes (p<0.001 for all) were higher in the IgAV-N patients than in the IgAV-woN patients. Among those markers, urinary IgA and IgM had the highest AUC (0.86 and 0.87 respectively, p<0.0001). This prospective cohort study furthers our understanding of the pathophysiology of IgAV. We identified biomarkers that are able to distinguish patients initially with or without nephritis. To conclude, serum Gd-IgA1 and urinary IgA, IgG, IgM, IL-6, IL-8, IL-10, and IgA-IgG and IgA-sCD89 complexes could identify IgAV pediatric patients with renal involvement at the time of diagnosis.

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

“…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].…”

“…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].…”

Rituximab treatment for IgA vasculitis: A systematic review

“…Various authors have reported higher serum IgA levels in IgA vasculitis patients than in control patients [11]. In our review it was difficult to make a comparison with these results, since most of our patients had no immunoglobulin analytical data, and in the 6 patients with the data only 2 showed elevated levels.…”

Association between histopathological changes and expression of selected microRNAs in skin of adult patients with IgA vasculitis

“…Various predictors of disease recurrence and severity, including GIT and kidney involvement, age, gender, and extent of purpura, have been identified in IgAV, but they cannot be regularly applied to an individual patient . In recent years, the search for biological markers has revealed that the abnormal levels of cytokines and immunoglobulins, the presence of immune complexes and aberrant IgA glycosylation in serum and urine of patients could aid in the diagnosis, monitoring and identification of patients with the severe form of IgAV …”

“…[5][6][7] In recent years, the search for biological markers has revealed that the abnormal levels of cytokines and immunoglobulins, the presence of immune complexes and aberrant IgA glycosylation in serum and urine of patients could aid in the diagnosis, monitoring and identification of patients with the severe form of IgAV. 8,9 Tissue infiltration by neutrophils is a major feature of IgAV. The higher percentage of neutrophils found in the peripheral blood of IgAV patients 9 might thus be related to the presence of neutrophils in skin and other affected organs.…”