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Open Access 01-10-2024 | Cryptococcosis | Research

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

Authors: Carlos A. Arango-Franco, Julian Rojas, Carolina Firacative, Mélanie Migaud, Clara Inés Agudelo, José Luis Franco, Jean-Laurent Casanova, Anne Puel, Jairo Lizarazo, Elizabeth Castañeda, Andrés A. Arias

Published in: Journal of Clinical Immunology | Issue 7/2024

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.

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Kwon-Chung KJ, Fraser JA, Doering TL, Wang Z, Janbon G, Idnurm A, et al. Cryptococcus neoformans and Cryptococcus gattii, the etiologic agents of cryptococcosis. Cold Spring Harb Perspect Med. 2014;4(7):a019760. https://doi.org/10.1101/cshperspect.a019760.CrossRefPubMedPubMedCentral

MacDougall L, Fyfe M, Romney M, Starr M, Galanis E. Risk factors for Cryptococcus gattii infection, British Columbia, Canada. Emerg Infect Dis. 2011;17(2):193–9. https://doi.org/10.3201/eid1702.101020.CrossRefPubMedPubMedCentral

Chen SC, Meyer W, Sorrell TC. Cryptococcus gattii infections. Clin Microbiol Rev. 2014;27(4):1024–980. https://doi.org/10.1128/CMR.00126-13.CrossRefPubMedPubMedCentral

Kwon-Chung KJ, Saijo T. Is Cryptococcus gattii a primary pathogen? J Fungi (Basel). 2015;1(2):154–67. https://doi.org/10.3390/jof1020154.CrossRefPubMed

Puel A, Bastard P, Bustamante J, Casanova JL. Human autoantibodies underlying infectious diseases. J Exp Med. 2022;219(4). https://doi.org/10.1084/jem.20211387.

Ku CL, Chi CY, von Bernuth H, Doffinger R. Autoantibodies against cytokines: phenocopies of primary immunodeficiencies? Hum Genet. 2020;139(6–7):783–94. https://doi.org/10.1007/s00439-020-02180-0.CrossRefPubMedPubMedCentral

Vinh DC. Of mycelium and men: inherent human susceptibility to fungal diseases. Pathogens. 2023;12(3). https://doi.org/10.3390/pathogens12030456.

Casanova JL, Peel J, Donadieu J, Neehus AL, Puel A, Bastard P. The ouroboros of autoimmunity. Nat Immunol. 2024;25(5):743–54. https://doi.org/10.1038/s41590-024-01815-y.CrossRefPubMed

Chetchotisakd P, Anunnatsiri S, Nithichanon A, Lertmemongkolchai G. Cryptococcosis in anti-interferon-gamma autoantibody-positive patients: a different clinical manifestation from HIV-infected patients. Jpn J Infect Dis. 2017;70(1):74–69. https://doi.org/10.7883/yoken.JJID.2015.340.CrossRefPubMed

10.

Pithukpakorn M, Roothumnong E, Angkasekwinai N, Suktitipat B, Assawamakin A, Luangwedchakarn V, et al. HLA-DRB1 and HLA-DQB1 are associated with adult-onset immunodeficiency with acquired anti-interferon-gamma autoantibodies. PLoS ONE. 2015;10(5):e0128481. https://doi.org/10.1371/journal.pone.0128481.CrossRefPubMedPubMedCentral

11.

Trapnell BC, Nakata K, Bonella F, Campo I, Griese M, Hamilton J, et al. Pulmonary alveolar proteinosis. Nat Rev Dis Primers. 2019;5(1):16. https://doi.org/10.1038/s41572-019-0066-3.CrossRefPubMed

12.

Lee E, Miller C, Ataya A, Wang T. Opportunistic infection associated with elevated GM-CSF autoantibodies: a case series and review of the literature. Open Forum Infect Dis. 2022;9(5):ofac146. https://doi.org/10.1093/ofid/ofac146.CrossRefPubMedPubMedCentral

13.

Rosen LB, Freeman AF, Yang LM, Jutivorakool K, Olivier KN, Angkasekwinai N, et al. Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis. J Immunol. 2013;190(8):3959–66. https://doi.org/10.4049/jimmunol.1202526.CrossRefPubMed

14.

Salvator H, Cheng A, Rosen LB, Williamson PR, Bennett JE, Kashyap A, et al. Neutralizing GM-CSF autoantibodies in pulmonary alveolar proteinosis, cryptococcal meningitis and severe nocardiosis. Respir Res. 2022;23(1):280. https://doi.org/10.1186/s12931-022-02103-9.CrossRefPubMedPubMedCentral

15.

Kuo CY, Wang SY, Shih HP, Tu KH, Huang WC, Ding JY, et al. Disseminated cryptococcosis due to anti-granulocyte-macrophage colony-stimulating factor autoantibodies in the absence of pulmonary alveolar proteinosis. J Clin Immunol. 2017;37(2):143–52. https://doi.org/10.1007/s10875-016-0364-4.CrossRefPubMed

16.

Chen GH, Teitz-Tennenbaum S, Neal LM, Murdock BJ, Malachowski AN, Dils AJ, et al. Local GM-CSF-dependent differentiation and activation of pulmonary dendritic cells and macrophages protect against progressive cryptococcal lung infection in mice. J Immunol. 2016;196(4):1810–21. https://doi.org/10.4049/jimmunol.1501512.CrossRefPubMed

17.

Prevel R, Guillotin V, Imbert S, Blanco P, Delhaes L, Duffau P. Central nervous system cryptococcosis in patients with sarcoidosis: comparison with non-sarcoidosis patients and review of potential pathophysiological mechanisms. Front Med (Lausanne). 2022;9:836886. https://doi.org/10.3389/fmed.2022.836886.CrossRefPubMed

18.

Escandon P, Lizarazo J, Agudelo CI, Castaneda E. Cryptococcosis in Colombia: compilation and analysis of data from laboratory-based surveillance. J Fungi (Basel). 2018;4(1). https://doi.org/10.3390/jof4010032.

19.

Lizarazo J, Escandón P, Agudelo CI, Firacative C, Meyer W, Castañeda E. Retrospective study of the epidemiology and clinical manifestations of Cryptococcus gattii infections in Colombia from 1997–2011. PLoS Negl Trop Dis. 2014;8(11):e3272. https://doi.org/10.1371/journal.pntd.0003272.CrossRefPubMedPubMedCentral

20.

Arango-Franco CA, Migaud M, Ramirez-Sanchez IC, Arango-Bustamante K, Moncada-Velez M, Rojas J, et al. Anti-GM-CSF neutralizing autoantibodies in Colombian patients with disseminated cryptococcosis. J Clin Immunol. 2023;43(5):921–32. https://doi.org/10.1007/s10875-023-01451-5.CrossRefPubMedPubMedCentral

21.

Firacative C, Escandón P. Antifungal susceptibility of clinical Cryptococcus gattii isolates from Colombia varies among molecular types. Med Mycol. 2021;59(11):1122–5. https://doi.org/10.1093/mmy/myab041.CrossRefPubMedPubMedCentral

22.

Becerra-Álvarez P, Escandón P, Lizarazo J, Quirós-Gómez Ó, Firacative C. Cryptococcus neoformans- and Cryptococcus gattii-specific IgG, IgA and IgM differ among children and adults with and without cryptococcosis from Colombia. Med Mycol. 2022;60(9). https://doi.org/10.1093/mmy/myac067.

23.

(INS) INdSdC. Tuberculosis en, Colombia. 2024. Proceso vigilancia y analisis del riesgo en salud pública [Internet]. https://www.ins.gov.co/buscador-eventos/Informesdeevento/TUBERCULOSIS%20PE%20III%202024.pdf.

24.

Bryson BD, Rosebrock TR, Tafesse FG, Itoh CY, Nibasumba A, Babunovic GH, et al. Heterogeneous GM-CSF signaling in macrophages is associated with control of Mycobacterium tuberculosis. Nat Commun. 2019;10(1):2329. https://doi.org/10.1038/s41467-019-10065-8.CrossRefPubMedPubMedCentral

25.

Rothchild AC, Stowell B, Goyal G, Nunes-Alves C, Yang Q, Papavinasasundaram K, et al. Role of granulocyte-macrophage colony-stimulating factor production by T cells during Mycobacterium tuberculosis infection. mBio. 2017;8(5). https://doi.org/10.1128/mBio.01514-17.

26.

Gonzalez-Juarrero M, Hattle JM, Izzo A, Junqueira-Kipnis AP, Shim TS, Trapnell BC, et al. Disruption of granulocyte macrophage-colony stimulating factor production in the lungs severely affects the ability of mice to control Mycobacterium tuberculosis infection. J Leukoc Biol. 2005;77(6):914–22. https://doi.org/10.1189/jlb.1204723.CrossRefPubMed

27.

Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020;370(6515). https://doi.org/10.1126/science.abd4585.

28.

Bastard P, Michailidis E, Hoffmann HH, Chbihi M, Le Voyer T, Rosain J, et al. Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine. J Exp Med. 2021;218(4). https://doi.org/10.1084/jem.20202486.

29.

Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020;370(6515). https://doi.org/10.1126/science.abd4570.

30.

Le Voyer T, Parent AV, Liu X, Cederholm A, Gervais A, Rosain J, et al. Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency. Nature. 2023;623(7988):803–13. https://doi.org/10.1038/s41586-023-06717-x.CrossRefPubMedPubMedCentral

31.

Rajasingham R, Govender NP, Jordan A, Loyse A, Shroufi A, Denning DW, et al. The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect Dis. 2022;22(12):1748–55. https://doi.org/10.1016/S1473-3099(22)00499-6.CrossRefPubMedPubMedCentral

32.

Coussement J, Heath CH, Roberts MB, Lane RJ, Spelman T, Smibert OC, et al. Current epidemiology and clinical features of cryptococcus infection in patients without human immunodeficiency virus: a multicenter Study in 46 hospitals in Australia and New Zealand. Clin Infect Dis. 2023;77(7):976–86. https://doi.org/10.1093/cid/ciad321.CrossRefPubMed

33.

Brizendine KD, Baddley JW, Pappas PG. Predictors of mortality and differences in clinical features among patients with cryptococcosis according to immune status. PLoS ONE. 2013;8(3):e60431. https://doi.org/10.1371/journal.pone.0060431.CrossRefPubMedPubMedCentral

34.

Hevey MA, George IA, Raval K, Powderly WG, Spec A. Presentation and mortality of cryptococcal infection varies by predisposing illness: a retrospective cohort study. Am J Med. 2019;132(8):977–e831. https://doi.org/10.1016/j.amjmed.2019.04.026.CrossRefPubMedPubMedCentral

35.

Fang W, Fa Z, Liao W. Epidemiology of Cryptococcus and cryptococcosis in China. Fungal Genet Biol. 2015;78:7–15. https://doi.org/10.1016/j.fgb.2014.10.017.CrossRefPubMed

36.

de Azambuja AZ, Wissmann Neto G, Watte G, Antoniolli L, Goldani LZ. Cryptococcal meningitis: a retrospective cohort of a Brazilian reference hospital in the post-HAART era of universal access. Can J Infect Dis Med Microbiol. 2018;2018:6512468. https://doi.org/10.1155/2018/6512468.CrossRefPubMedPubMedCentral

37.

Nunes JO, Tsujisaki RAS, Nunes MO, Lima GME, Paniago AMM, Pontes ERJC, et al. Cryptococcal meningitis epidemiology: 17 years of experience in a state of the Brazilian pantanal. Rev Soc Bras Med Trop. 2018;51(4):485–92. https://doi.org/10.1590/0037-8682-0050-2018.CrossRefPubMed

38.

Lomes NR, Melhem MS, Szeszs MW, Martins MA, Buccheri R. Cryptococcosis in non-HIV/non-transplant patients: a Brazilian case series. Med Mycol. 2016;54(7):669–76. https://doi.org/10.1093/mmy/myw021.CrossRefPubMed

39.

Debourgogne A, Iriart X, Blanchet D, Veron V, Boukhari R, Nacher M, et al. Characteristics and specificities of cryptococcus infections in French Guiana, 1998–2008. Med Mycol. 2011;49(8):864–71. https://doi.org/10.3109/13693786.2011.584198.CrossRefPubMed

40.

Yang DH, England MR, Salvator H, Anjum S, Park YD, Marr KA, et al. Cryptococcus gattii species complex as an opportunistic pathogen: underlying medical conditions associated with the infection. mBio. 2021;12(5):e0270821. https://doi.org/10.1128/mBio.02708-21.CrossRefPubMed

Title: Autoantibodies Neutralizing GM-CSF in HIV-Negative Colombian Patients Infected with Cryptococcus gattii and C. neoformans
Authors: Carlos A. Arango-Franco
Julian Rojas
Carolina Firacative
Mélanie Migaud
Clara Inés Agudelo
José Luis Franco
Jean-Laurent Casanova
Anne Puel
Jairo Lizarazo
Elizabeth Castañeda
Andrés A. Arias
Publication date: 01-10-2024
Publisher: Springer US
Keywords: Cryptococcosis
Human Immunodeficiency Virus
Cytokines
Published in: Journal of Clinical Immunology / Issue 7/2024
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-024-01757-y

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

Abstract

Background

Methods

Results

Conclusions

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Abstract

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