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. 2024 Jul 15;44(7):163.
doi: 10.1007/s10875-024-01757-y.

Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans

Carlos A Arango-Franco #  1   2 , Julian Rojas #  3 , Carolina Firacative  4 , Mélanie Migaud  5 , Clara Inés Agudelo  6 , José Luis Franco  3 , Jean-Laurent Casanova  5   7   8   9   10 , Anne Puel #  5   7   8 , Jairo Lizarazo #  11 , Elizabeth Castañeda #  6 , Andrés A Arias #  12   13
Affiliations

Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans

Carlos A Arango-Franco et al. J Clin Immunol. .

Abstract

Background: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016.

Methods: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans).

Results: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans.

Conclusions: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.

Keywords: Cryptococcus gattii; Cryptococcus neoformans; Anti-cytokine autoantibodies; Cryptococcosis; Granulocyte-macrophage colony-stimulating factor (GM-CSF); Human immunodeficiency virus (HIV), Neutralizing auto-abs against GM-CSF.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Detection of IgG auto-Abs in patients with cryptococcosis. Multiplex particle-based assay for auto-Abs against GM-CSF, IL-17 A, IL-6, IFN-α, IFN-β, IFN-γ, IFN-ω, IL-23, and IL-12p40 in serum from patients with cryptococcosis (n = 30) (P1 to P30), healthy controls (n = 4), and a patient positive for auto-Ab against each cytokine. HC, healthy controls; C, positive controls for each cytokine; P, patients with cryptococcosis
Fig. 2
Fig. 2
Neutralizing anti GM-CSF auto-Abs in patients with cryptococcosis caused by Cryptococcus gattii or Cryptococcus neoformans. Monoparametric histogram showing the STAT5 phosphorylation (pSTAT5), as assessed by flow cytometry, upon the stimulation with recombinant human (rh)GM-CSF (red) or rhIL-3 (grey) of control PBMCs, in the absence of serum, or in the presence of a 1:10 dilution of serum from two healthy individuals (HC-1 and HC-2), from two individuals previously described to carry neutralizing auto-Abs against GM-CSF (C-1 and C-2) or from thirty patients with cryptococcosis (P1 to P30). a Patients with cryptococcosis caused by C. gattii or, b patients with cryptococcosis caused by C. neoformans. Not stimulated (NS) PBMCs were used as the basal STAT5 phosphorylation (black line). c Dot Plot showing p-STAT5 mean fluorescence intensity (MFI) of PBMCs, NS or stimulated with rhGM-CSF or rhIL-3 in the presence of 10% of plasma from healthy controls, individuals with or without anti-GM-CSF auto-Abs from a and b. HC, healthy controls; C, positive control for anti-GM-CSF neutralizing auto-Abs; P, patients with cryptococcosis; NS, not stimulated. The figure is representative of three independent experiments
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