Serum autoantibodies predict IgA nephropathy disease progression

By Ingrid Grasmo, medwireNews Reporter

Study findings reveal that increasing serum levels of immunoglobulin (Ig)G and IgA autoantibodies act as markers for progression of IgA nephropathy (IgAN).

The findings, published in the Journal of the American Society of Nephrology, may help in the diagnosis and management of this common kidney disease, since it is often difficult to predict the long-term clinical outcome for patients with IgAN.

"This paper is a first step, and in the future we have to refine these tests to check the impact of different treatments on these serum biomarkers, and to imagine new therapies with direct impact on modified IgA1 or on the specific antibody responses against it," said lead study author Francois Berthoux (University North Hospital, Saint Etienne, France) in a press release.

Galactose-deficient (Gd)-IgA1, also referred to as autoantigen, analysis of serum samples obtained at diagnosis from 97 IgAN patients, aged on average 43.6 years, and 60 healthy controls revealed that patients had significantly higher mean serum levels of IgA (2.88 vs 2.10 mg/mL), Gd-IgA1 (92.6 vs 69.9 U/mL), normalized IgG autoantibody (1.48 vs 1.24 once daily (OD) per 0.5 µg), and total IgA autoantibody (2.33 vs 1.42 U/mL).

The study also showed that serum levels of Gd-IgA, normalized IgG autoantibody, and total IgA autoantibody increased progressively with worsening clinical outcomes, with relative levels of 71.4-107.8 U/ml, 1.08-2.05 OD per 0.5 µg, and 1.59-2.88 U/ml for absolute renal risk (ARR) scores from 0 to 3.

Berthoux and team note this is the first report of an association of serum IgG and IgA autoantibodies with ARR scoring, which "is consistent with a multi-hit hypothesis for the disease mechanisms of IgAN, wherein an increased serum level of autoantigen alone is not sufficient to induce renal injury."

Over an average 13.8-year follow up, regression analysis showed that both IgA and IgG autoantibody levels prospectively predicted dialysis or death. Further analysis showed that worse survival was seen in IgAN patients with serum IgG autoantibody levels of 1.33 OD per 0.5 µg or above compared with those with lower levels, at 76% and 56% versus 94% and 80% at 5 and 10 years' postdiagnosis, respectively.

However, the discriminating power for high or very high risk for progression to dialysis or death was greater for IgG autoantibody compared with IgA autoantibody, with a net reclassification index of more than 93%.

The researchers caution that a direct causal relationship between serum levels of autoantigen or autoantibodies with disease progression cannot be inferred from the study, and requires a longitudinal study with serial biomarker measurements.

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