期刊
JOURNAL OF CLINICAL IMMUNOLOGY
卷 37, 期 2, 页码 143-152出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10875-016-0364-4
关键词
Granulocyte-macrophage colony-stimulating factor; anti-cytokine autoantibodies; cryptococcal infection; opportunistic infection
类别
资金
- Ministry of Science and Technology [MOST 104-2314-B-182A-042]
- Chang Gung Memorial Hospital [CMRPG3D0281, BMRPE44]
Introduction Autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can cause acquired pulmonary alveolar proteinosis (PAP). Cases of acquired PAP susceptible to typical respiratory pathogens and opportunistic infections have been reported. Anti-GM-CSF autoantibodies have been reported in a few patients with cryptococcal meningitis. This study evaluated the presence of neutralizing antiGM- CSF autoantibodies in patients without known congenital or acquired immunodeficiency with severe pulmonary or extrapulmonary cryptococcal infection but without PAP. Methods We took a clinical history and performed an immunologic evaluation and screening of anti-cytokine autoantibodies in patients with cryptococcal meningitis. The impact of autoantibodies to GM-CSF on immune function was assessed by intracellular staining of GM-CSF-induced STAT5 phosphorylation and MIP-1 alpha production in normal peripheral blood mononuclear cells incubated with plasma from patients or normal control subjects. Results Neutralizing anti-GM-CSF autoantibodies were identified in four patients with disseminated cryptococcosis, none of whom exhibited PAP. Plasma from patients blocked GMCSF signaling and inhibited STAT5 phosphorylation and production of MIP-1 alpha. One patient died of disseminated cryptococcosis involving the central nervous system, which was associated with defective GM-CSF activity. Conclusions Anti-GM-CSF autoantibodies increase susceptibility to cryptococcal infection in adults without PAP. Cryptococcal central nervous system infection associated with anti-GM-CSF autoantibodies could result in neurological sequelae or be life-threatening. Therefore, timely detection of neutralizing anti-GM-CSF autoantibodies and development of an effective therapy are necessary to prevent deterioration of cryptococcal infection in these patients.
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