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.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
Funding support by the Indian Council of Medical Research [Advanced Center for Research in Pediatric Kidney Diseases; 5/7/1090/2013-RHN and 5/4/7–18/Nephro/2020-NCDII (2020-4727)] and Department of Biotechnology, Government of India [BT/PR11030/MED/30/1644/2016].
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Indira Agarwal, Christian Medical College, Vellore; Vinay Aggarwal, BL Kapoor Hospital, New Delhi; Uma Ali, Bai Jerbai Wadia Hospital for Children, Mumbai; Kanav Anand, Sir Ganga Ram Hospital, New Delhi; Arvind Bagga, All India Institute of Medical Sciences, New Delhi; Chinmay Behera, Kalinga Institute of Medical Sciences, Bhubaneswar; Gurdeep Singh Dhooria, Dayanand Medical College & Hospital, Ludhiana; Sriram Krishnamurthy, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry; Manish Kumar and Kirtisudha Mishra, Chacha Nehru Bal Chikitsalaya, Delhi; Amarjeet Mehta, Sawai Man Singh Hospital, Jaipur; Narayan Prasad, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow; Padmaraj Rajendran, Institute of Child Health, Chennai; VK Sairam, Kanchi Kamacoti Child Trust Hospital, Chennai; Sidharth Kumar Sethi, Medanta The Medicity, Gurugram; Rajiv Sinha, Institute of Child Health, Kolkata; Nilam Thaker, Ahmedabad; Anil Vasudevan, St. John’s Medical College and Hospital, Bangalore; Susan Uthup, Trivandrum Medical College, Thiruvananthapuram.
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Khandelwal, P., Nambiar, S., Saini, R. et al. Anti-factor B antibodies in atypical hemolytic uremic syndrome. Pediatr Nephrol 39, 1909–1916 (2024). https://doi.org/10.1007/s00467-024-06284-x
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DOI: https://doi.org/10.1007/s00467-024-06284-x