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

Disseminated Cryptococcosis Following Eculizumab Therapy: Insight Into Pathogenesis

Olivier Lortholary  1   2   3 , Carine El-Sissy  4   5 , Jérémie Leporrier  1 , Sarah Sze Wah Wong  2 , Eric Dannaoui  6 , Véronique Fremeaux-Bacchi  4   5 , Vishukumar Aimanianda  2
Affiliations

Disseminated Cryptococcosis Following Eculizumab Therapy: Insight Into Pathogenesis

Olivier Lortholary et al. Open Forum Infect Dis. .

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.

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Conflict of interest statement

Potential conflicts of interest. For all the authors, there is no conflict to declare.

Figures

Figure 1.
Figure 1.
A, Complement assay results. B and C, C5a and C5 levels in the serum of a patient who underwent eculizumab therapy and healthy donors (n = 4). D and E, Interleukin 8 released by peripheral blood mononuclear cells and neutrophils, respectively, isolated from patient blood samples (collected twice, 18 November 2021 and 21 February 2022), stimulated with Cryptococcus neoformans for 1–5 days in RPMI with autologous serum (AuS) or normal human serum; AuS obtained from patient's blood collected on 18 November 2021 was used for the assay, with technical replication. ***P < .001; ****P < .0001. Abbreviations: AuS, autologous serum; CH50, 50% hemolytic complement activity assay; Crypto, Cryptococcus neoformans; FH, factor H; FI, factor I; IL, interleukin; ND, not determined; Neutro, neutrophils; NHS, normal human serum; PBMC, peripheral blood mononuclear cells.
Figure 2.
Figure 2.
A, C5a generated from human C5 treated with Cryptococcus neoformans (H99 strain) at specified interaction times. B, Heat-killed C neoformans (H99) failed to release C5a from C5. C, Lytic activity of the culture supernatant (CS) of C neoformans (H99) incubated in collagen medium for 24 hours, against different complement proteins. D, C5a generating activity of C neoformans isolated from the patient. E, Postulated mechanism of C neoformans infection following eculizumab treatment. ****P < .0001.
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