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22-01-2024 | Hemolytic Uremic Syndrome | Original Article

Anti-factor B antibodies in atypical hemolytic uremic syndrome

Authors: Priyanka Khandelwal, Shreesha Nambiar, Rahul Saini, Savita Saini, Poonam Coshic, Aditi Sinha, Pankaj Hari, Jayanth Kumar Palanichamy, Arvind Bagga

Published in: Pediatric Nephrology | Issue 6/2024

Abstract

Background

The etiology of atypical hemolytic uremic syndrome (aHUS) is unknown in 30–40% of patients. Anti-factor B (FB) antibodies are reported in C3 glomerulopathy (C3G) and immune-complex membranoproliferative glomerulonephritis (IC-MPGN), though not in aHUS.

Methods

We screened patients < 18-year-old from cohorts of aHUS and C3G/idiopathic IC-MPGN. Anti-FB IgG antibodies were measured by ELISA and confirmed by Western blot. Normative levels were based on antibody levels in 103 healthy blood donors.

Results

Prevalence of anti-FB antibodies was 9.7% (95% CI 6.1–14.5%; n = 21) in 216 patients with aHUS, including 11.5% (95% CI 6.4–18.5%; n = 14) in anti-FH associated aHUS and 11.8% (95% CI 4.4–23.9%; n = 6) in patients without a definitive genetic or autoimmune etiology. Patients with significant genetic variants did not show anti-FB antibodies. In patients with concomitant anti-FB and anti-FH antibodies, median anti-FH titers were higher (11,312 AU/mL vs. 4920 AU/mL; P = 0.04). Anti-FB antibody titer correlated with disease severity (hemoglobin and platelets; P < 0.05), declined following plasma exchange and increased during relapse. While 4/64 patients with C3G (6.3%) and 1/17 with IC-MPGN showed anti-FB antibodies, titers were higher in aHUS (544.8 AU/mL vs. 1028.8 AU/mL; P = 0.003).

Conclusion

Anti-FB antibodies are present in 6–10% of patients with aHUS and C3G/IC-MPGN, with higher titers in the former. The diagnostic and therapeutic implication of anti-FB antibodies in aHUS needs confirmation and further studies. The study shows propensity for autoantibody generation and co-existence of multiple risk factors for aHUS in Indian children.

Graphical abstract

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Title: Anti-factor B antibodies in atypical hemolytic uremic syndrome
Authors: Priyanka Khandelwal
Shreesha Nambiar
Rahul Saini
Savita Saini
Poonam Coshic
Aditi Sinha
Pankaj Hari
Jayanth Kumar Palanichamy
Arvind Bagga
Publication date: 22-01-2024
Publisher: Springer Berlin Heidelberg
Keywords: Hemolytic Uremic Syndrome
Glomerulonephritis
Thrombotic Microangiopathy
Published in: Pediatric Nephrology / Issue 6/2024
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-024-06284-x

At a glance: The STEP trials

Springer Medicine

Anti-factor B antibodies in atypical hemolytic uremic syndrome

Abstract

Background

Methods

Results

Conclusion

Graphical abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Graphical abstract

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