RECURRENT CRYPTOCOCCAL MENINGITIS IN PATIENT WITH ANTI-GM-CSF AUTOANTIBODIES

Abstract

<h3>Introduction</h3> Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor and pro-inflammatory cytokine. The involvement of anti-GM-CSF autoantibodies in the development of protein alveolar proteinosis (PAP) has been previously elucidated, however its role in increasing susceptibility to opportunistic infections remains less clear. <h3>Case Description</h3> A 33 year-old previously healthy man developed recurrent disseminated cryptococcal infections. He was hospitalized several times due to severe headaches and detection of cryptococcal antigen in his serum and CSF. He underwent multiple courses of antifungal induction therapy followed by antifungal prophylaxis and dexamethasone taper, yet remained symptomatic with persistent cryptococcal antigen in his CSF. Blood work was notable for the presence of anti-GM-CSF autoantibodies, low IgG (463), low IgM (26), normal IgA (69), 3/23 protective pneumococcal titers, and normal tetanus/diphtheria antibodies. Flow cytometry is currently pending. <h3>Discussion</h3> Anti-GM-CSF autoantibodies neutralize cell signaling resulting in impaired phagocytosis and host immune responses. Autoantibodies against GM-CSF increase susceptibility to opportunistic infections, particularly cryptococcal meningitis, in otherwise immunocompetent patients via the inhibition of GM-CSF STAT5 phosphorylation and GM-CSF-induced MIP-1alpha protein production. This is a rare case of a patient who developed recurrent cryptococcal meningitis in the setting of anti-GM-CSF autoantibodies and hypogammaglobulinemia. Further workup is underway to explore the possibility of concurrent CVID versus secondary hypogammaglobulinemia due to prolonged dexamethasone tapers. Patients with recurrent cryptococcal infections should be screened for anti-GM-CSF autoantibodies, which can help tailor treatment including GM-CSF therapy and anti-CD20 therapy. Patients would also benefit from a basic immunologic workup and routine screening for PAP.