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Kidney Week

Abstract: FR-PO651

Nephritic Factor-Like Autoantibodies Are Present in Unaffected Children

Session Information

  • Pediatric Nephrology - II
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1900 Pediatric Nephrology

Authors

  • Culek, Christopher, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
  • Nester, Carla Marie, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
Background

We previously reported that C3-convertase targeted autoantibodies (nephritic factor-like antibodies) were highly prevalent in normal young adults (publication pending). In this study, we explore the prevalence of these convertase-directed antibodies in the pediatric population.

Methods

We measured the binding and stabilization of the C3-convertase and it’s proenzyme by normal human IgG purified from plasma samples. We selected samples for three age cohorts: one, five, and ten-year-olds. Binding was determined using surface plasmon resonance with C3b was immobilized as the surface ligand. Each purified antibody was tested in four analyte conditions: IgG alone, IgG with FB (proconvertase), IgG with FD, and IgG with FB and FD (convertase). These conditions were compared to four control conditions: buffer alone, FB alone, FD alone, and FB with FD. Response (in RUs) was recorded at 20 seconds post-injection to measure binding and at 200 seconds post-injection to evaluate stabilization.

Results

Binding and stabilization results were mixed. All three age cohorts (1, 5, 10 years) show a statistically significant increase in binding for IgG+FB (proconvertase) vs FB alone at 20 seconds post-injection (two-tailed students t-test values of 0.002, 0.004, and 0.007, respectively). However, none of the cohorts show statistical significance at 200 seconds (t-test results of 0.49, 0.13, and 0.41). Significant binding was observed in the IgG+FB+FD samples compared to FB+FD at both 20- and 200-seconds post-injection for all age groups. Review of the data shows strong positive results (increasing reagent response by >20%) in 16 individuals for the convertase and 20 individuals for the proconvertase.

Conclusion

Our data suggests that convertase- and proconvertase-directed antibodies exist in pediatric cohorts. The prevalence is less than what we previously reported in adults (29/30 individuals were positive for both antigens). Whether this indicates the de novo emergence of this antibody over time or class switching of an IgM to an IgG over time is currently under investigation. Determining an origin for nephritic factors is an important research goal in complement-mediated kidney disease. Identifying non-pathogenic antibodies that share the convertase antigen may provide an origin for nephritic factors.

Funding

  • NIDDK Support