Disseminated Cryptococcosis Following Eculizumab Therapy: Insight Into Pathogenesis

Olivier Lortholary; Carine El-Sissy; Jérémie Leporrier; Sarah Sze Wah Wong; Eric Dannaoui; Véronique Fremeaux-Bacchi; Vishukumar Aimanianda

doi:10.1093/ofid/ofad159

Disseminated Cryptococcosis Following Eculizumab Therapy: Insight Into Pathogenesis

Open Forum Infect Dis. 2023 Mar 24;10(4):ofad159. doi: 10.1093/ofid/ofad159. eCollection 2023 Apr.

Authors

Olivier Lortholary^{1

2

3}, Carine El-Sissy^{4

5}, Jérémie Leporrier¹, Sarah Sze Wah Wong², Eric Dannaoui⁶, Véronique Fremeaux-Bacchi^{4

5}, Vishukumar Aimanianda²

Affiliations

¹ Department of Infectious Diseases and Tropical Medicine, Necker-Enfants Malades University Hospital, Centre d'Infectiologie Necker-Pasteur, Assistance Publique-Hôpitaux de Paris, Université de Paris Cité, Paris, France.
² Institut Pasteur, Molecular Mycology Unit, Department of Mycology, Université Paris Cité, Paris, France.
³ Institut Pasteur, National Reference Center for Invasive Mycoses and Antifungals, Paris, France.
⁴ Inserm UMRS1138, Centre de Recherche des Cordeliers, Team "Inflammation, Complement and Cancer," Paris, France.
⁵ Department of Immunology, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁶ Parasitology-Mycology Unit, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris Cité, Paris, France.

Abstract

Eculizumab, a recombinant humanized monoclonal antibody (mAb), is used for the treatment of patients (both adults and children) with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. This mAb binds to complement protein 5 (C5), thereby inhibiting its cleavage. On the other hand, one of the C5 cleavage products, C5a, is a potent anaphylatoxin with proinflammatory properties, involved in antimicrobial surveillance. Administration of eculizumab has been reported to make patients more susceptible to infection by encapsulated bacteria. Here, we are reporting an adult case of disseminated infection due to the encapsulated yeast Cryptococcus neoformans following eculizumab therapy and discuss its pathogenesis.

Keywords: aHUS; atypical hemolytic uremic syndrome; complement component c5; cryptococcosis; eculizumab; pathogenesis.