Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2024 Jan 19:rs.3.rs-3873029.
doi: 10.21203/rs.3.rs-3873029/v1.

Autoantibodies neutralizing GM-CSF in HIV-negative Colombian patients infected with Cryptococcus gattii and C. neoformans

Carlos A Arango-Franco  1 , Julián Rojas  1 , Carolina Firacative  2 , Clara Inés Agudelo  3 , José Luis Franco  1 , Jean-Laurent Casanova  4 , Anne Puel  4 , Jairo Lizarazo  5 , Elizabeth Castañeda  3 , Andrés A Arias  1
Affiliations

Autoantibodies neutralizing GM-CSF in HIV-negative Colombian patients infected with Cryptococcus gattii and C. neoformans

Carlos A Arango-Franco et al. Res Sq. .

Update in

Abstract

Background: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Autoantibodies (auto-Abs) neutralizing 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 from Colombian patients with non-HIV related cryptococcosis in a retrospective national cohort collected from 1997 to 2016.

Methods: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs in 30 HIV (-) adults presenting cryptococcosis (13 by C. gattii, and 17 by C. neoformans).

Results: We detected auto-Abs neutralizing GM-CSF in the plasma of 9 out of 13 (69%) patients infected with C. gattii and 1 out of 17 (6%) patients with C. neoformans.

Conclusions: We report ten Colombian patients with cryptococcosis due to auto-Abs neutralizing GM-CSF. Nine of the ten patients were infected with C. gattii, and only one with C. neoformans.

Keywords: Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; GM-CSF autoantibodies; Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF); HIV-negative patients; Mycobacterium tuberculosis (Mtb); Pulmonary tuberculosis (Tb); anti-cytokine autoantibodies; autoantibodies (auto-Abs) neutralizing GM-CSF; human immunodeficiency virus (HIV).

PubMed Disclaimer

Conflict of interest statement

Potential conflicts of interest. The authors do not reported conflicts of interest. A.A.A, C.A.A.F, A.P, J.-L.C, J.L.F, J.R.S, J.L, C.I.A, C.F and E.C conceived the research. C.I.A, J.L and E.C collect the samples. C.A.A.F designed and performed the experiments. A.A.A, C.A.A.F, J.R.S, C.F, C.I.A, J.L and E.C interpreted and analyze data, wrote the manuscript, generated figures, and tables. All the authors discussed and reviewed the manuscript and approved its submission. The authors have no competing interest to declare.

Figures

Figure 1
Figure 1. Neutralizing GM-CSF auto-Abs in patients with cryptococcosis by Cryptococcus gattii.
STAT5 phosphorylation (p-STAT5), assessed by flow cytometry, upon the stimulation with recombinant human rhGM-CSF (red) or rhIL-3 (black) of control PBMCs, in the absence of sera, or in the presence of 1:10 dilution of sera from two healthy individuals (HC-1 and HC-2), sera of two individuals previously described carrying GM-CSF auto-Abs (C-1 and C-2) or from thirteen patients with cryptococcosis by C. gattii. NS: non-stimulated with rhGM-CSF or rhIL-3.
Figure 2
Figure 2. Neutralizing GM-CSF auto-Abs in patients with cryptococcosis by Cryptococcus neoformans.
STAT5 phosphorylation (p-STAT5), assessed by flow cytometry, upon the stimulation with recombinant human rhGM-CSF (red) or rhIL-3 (black) of control PBMCs, in the absence of sera, or in the presence of a 1:10 dilution of serum from two healthy individuals (HC-1 and HC-2), sera of two individuals previously described carrying GM-CSF auto-Abs (C-1 and C-2) or from seventeen patients with cryptococcosis by C. neoformans. NS: non-stimulated with rhGM-CSF or rhIL-3.
See this image and copyright information in PMC

References

    1. Kwon-Chung KJ, et al. Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis. Cold Spring Harb Perspect Med. 2014;4(7):a019760. - PMC - PubMed
    1. MacDougall L, et al. Risk factors for Cryptococcus gattii infection, British Columbia, Canada. Emerg Infect Dis. 2011;17(2):193–9. - PMC - PubMed
    1. Kwon-Chung KJ, Saijo T. Is J Fungi (Basel). 2015;1(2):154–67. - PMC - PubMed
    1. Chen SC, Meyer W, Sorrell TC. Cryptococcus gattii infections. Clin Microbiol Rev. 2014;27(4):980–1024. - PMC - PubMed
    1. Puel A et al. Human autoantibodies underlying infectious diseases. J Exp Med, 2022. 219(4). - PMC - PubMed

Publication types

LinkOut - more resources