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Anti-factor B antibodies in atypical hemolytic uremic syndrome

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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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Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, ICMR Center for Advanced Research in Nephrology, All India Institute of Medical Sciences, New Delhi, India

    Priyanka Khandelwal, Shreesha Nambiar, Rahul Saini, Savita Saini, Aditi Sinha, Pankaj Hari & Arvind Bagga

  2. Department of Transfusion Medicine and Blood Bank, All India Institute of Medical Sciences, New Delhi, India

    Poonam Coshic

  3. Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India

    Jayanth Kumar Palanichamy

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  1. Priyanka Khandelwal
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Contributions

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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Correspondence to Arvind Bagga.

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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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