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Anti-GM-CSF Neutralizing Autoantibodies in Colombian Patients with Disseminated Cryptococcosis
Carlos A Arango-Franco1,2, Mélanie Migaud1,3, Isabel Cristina Ramírez-Sánchez4,5
1Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale (INSERM) U1163, Necker Hospital for Sick Children, 24 Boulevard du Montparnasse, Paris, France.
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.
Insights
Three Colombian patients with disseminated cryptococcosis had high levels of neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). This finding suggests a potential role for anti-GM-CSF autoantibodies in this fungal infection.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Cryptococcosis is a serious fungal infection caused by Cryptococcus yeasts.
- Cryptococcal meningitis is the most common human manifestation.
- Neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) are linked to cryptococcal meningitis.
Conclusions:
- Disseminated cryptococcosis in these patients was associated with neutralizing autoantibodies against GM-CSF.
- Further research is needed on the genetic basis of autoantibody production and the GM-CSF pathway's role in Cryptococcus infections.
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