Acute postinfectious glomerulonephritis (APIGN) and C3 glomerulopathy (C3G) are both characterized by low serum C3 levels at diagnosis. However, this decrease is transient in patients with APIGN, whereas C3 levels are persistently low in patients with C3G, who also have a worse prognosis. Anti-factor B (anti-FB) autoantibodies might be involved in the pathogenesis of APIGN, according to new findings by Véronique Frémeaux-Bacchi and colleagues.

The researchers analysed a cohort of 34 children with APIGN and noted that at diagnosis, anti-FB antibodies were detectable in 91% of patients, compared with 14% of children diagnosed with C3G (n = 28); C3 levels were similarly low in both groups. “We believe that screening for anti-FB antibodies in all patients diagnosed with APIGN might help discriminate patients at risk of developing C3G from those with APIGN,” remarks Frémeaux-Bacchi.

In patients with APIGN, anti-FB levels, which decreased over time, correlated negatively with C3 levels and positively with soluble C5b-9 levels. Incubation of normal human serum with IgG from patients or healthy individuals indicated that anti-FB antibodies enhance the activation of C3 and C5 convertases. Epitope mapping identified hotspot antibody-binding sequences in FB and revealed that antibodies specific for epitopes near the catalytic domain of FB were associated with less-severe disease. “These observations might explain the deposition of C3 that we observe in the kidneys of patients with APIGN,” concludes Frémeaux-Bacchi.

Streptococcus was the most common cause of infection in patients with APIGN. “We failed to identify molecular mimicry between streptococcal antigens and FB, which suggests that a more complex mechanism underlies the pathogenesis of APIGN,” explains Frémeaux-Bacchi. “We aim to identify which nephritogenic streptococcal strains are associated with anti-FB antibody formation and test their ability to activate complement in the presence of these antibodies.”