Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis

Author:

Arango-Franco Carlos A.,Migaud Mélanie,Ramírez-Sánchez Isabel Cristina,Arango-Bustamante Karen,Moncada-Vélez Marcela,Rojas Julián,Gervais Adrian,Patiño-Giraldo Santiago,Perez-Zapata Lizeth J.,Álvarez Álvarez Jesús A.,Orrego Julio César,Roncancio-Villamil Gustavo,Boisson-Dupuis Stéphanie,Jouanguy Emmanuelle,Abel Laurent,Casanova Jean-Laurent,Bustamante Jacinta,Arias Andrés A.,Franco José Luis,Puel AnneORCID

Abstract

Abstract Background Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte–macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. Methods We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. Results Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. Conclusions We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.

Funder

Departamento Administrativo de Ciencia, Tecnología e Innovación

ECOS-NORD

Comité para el desarrollo de la investigación CODI UdeA

ESID European Society for Immunodeficiencies

Fundación “Diana-García de Olarte” para las Inmunodeficiencias Primarias (FIP

National Institutes of Health

NIH Clinical and Translational Science Award

French National Research Agency

Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence

Cross Lab Imagine Grant

French Foundation for Medical Research

Publisher

Springer Science and Business Media LLC

Subject

Immunology,Immunology and Allergy

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