Recurrent IgA nephropathy is predicted by altered glycosylated IgA, autoantibodies and soluble CD89 complexes

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, frequently leads to end-stage renal disease and kidney transplantation. However, disease recurrence often occurs after transplantation. Here we evaluated the predictive value of three markers for IgAN recurrence: the presence of galactose-deficient IgA1, IgG anti-IgA autoantibodies, and IgA-soluble (s) CD89 complexes. This was analyzed in 38 kidney transplant recipients with IgAN recurrence and compared with 22 patients transplanted for IgAN but without recurrence and with 17 healthy controls. Pre-transplantation galactose-deficient IgA1 serum levels were significantly higher in the recurrence compared with the no recurrence or control groups. IgA–IgG complexes were significantly elevated in the recurrence group. Both the recurrence and no recurrence groups had increased values of IgA–sCD89 complexes compared with healthy controls, but values were significantly lower in patients with recurrence compared with no recurrence. Areas under the receiver operating curve of the markers in pre-transplantation sera were 0.86 for galactose-deficient-IgA, 0.82 for IgA–IgG, and 0.78 for sCD89–IgA; all significant. Disease recurrence was associated with decreased serum galactose-deficient IgA1 and appearance of mesangial-galactose-deficient IgA1 deposits, whereas increased serum IgA–sCD89 complexes were associated with mesangial sCD89 deposits. Thus, galactose-deficient-IgA1, IgG autoantibodies, and IgA–sCD89 complexes are valuable biomarkers to predict disease recurrence, highlighting major pathogenic mechanisms in IgAN.

Laureline Berthelot, Thomas Robert, Vincent Vuiblet, Thierry Tabary, Antoine Braconnier, Moustapha Dram?, Olivier Toupance, Philippe Rieu, Renato C Monteiro and Fatouma Tour?

Reference: Kidney Int 88: 815-822; advance online publication, June 10, 2015; doi:10.1038/ki.2015.158

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