**6. Biomarkers**

The search for diagnostic and prognostic biomarkers is based on the above-mentioned physio pathological mechanisms. Finding biomarkers able to identify, at an early stage, patients at risk of renal progression, those who will need treatment, is a challenge.

Most of these studies focused on either IgAN or IgAV, but rarely both in the same study, as shown in Table 2.


**Table 2.** Potent value of biomarkers correlated to clinical and/or histological activity and outcome evaluated in IgAN and IgAV or both [ref].

Nevertheless, it is now accepted that the aberrantly glycosylated IgA1 (GdIgA1) plays a central role. Several methods are available to highlight and quantify GdIgA1. Mass spectrometry is the reference method, but it is difficult to use in current practice. The Helix aspersa agglutinin (HAA) lectin method is the most commonly used but lacks sensitivity, specificity and reproductivity [87]. Recently, the Japanese Suzuki team has developed a novel lectin-independent method with a specific monoclonal antibody (KM55 mAb) for measuring serum level of GdIgA1, that is clearly more performant and robust [88]. This team first showed that serum IgA, GdIgA1, and immune complexes containing GdIgA1 were increased in patients with IgAN but not in healthy subjects. The IgG anti-GdIgA1 antibody was particularly efficient in this study to make the diagnosis of IgAN since its sensitivity was 89% and its specificity was 92% (compare to the reference test HAA lectin method).

In IgAV, GdIgA1 (measured by HAA lectin method) and immunes complexes containing GdIgA1 are also increased in case of nephritis in children [78] and adults [77]. The team then used their GdIgA1-specific monoclonal antibody KM55 to highlight GdIgA1 in the glomeruli of 48 patients with IgAN and 14 patients with IgAV while it remains undetectable in the glomeruli of 35 with other glomerulopathies in which glomerular IgA deposit is frequent (lupus nephritis, HCV-related nephropathy, mesangio-proliferative glomerulonephritis, membranous nephropathy, hepatic glomerulosclerosis) [74].

Another team analyzed adult patients with renal-biopsy proven IgAN and IgAV. Serum GdIgA1 levels and glomerular GdIgA1 staining, using enzyme-linked immunosorbent essay (ELISA) with the same anti-human GdIgA1 specific monoclonal antibody (KM55), were comparable among patients with IgAN and IgAV [40].
