Anti-cytokine autoantibodies have been shown to be an important mediator of certain serious diseases including immunodeificncy due to anti-IFNg autoantibodies and pulmonary alveolar proteinosis due to anti-GM-CSF autoantibodies. Some patients are refractory to optimized conventional therapy or have serious intolerance to standard approaches. We will be enrolling patients with anticytokine autoantibody syndromes who have have progressive disease despite optimized conventional treatment. We will treat patients and collect their blood and evaluate disease-affected regions however appropriate, i.e. imaging for anti-IFNg-autonantibody associated deep-seated infections, endoscopy for anti-IL-17-autoantibody-associated candidiasis, bronchoscopy or CT imaging for GM-CSF autoantibody associated pulmonary alveolar proteinosis. We will evaluate blood for changes in autoantibody levels using out luminex-based method for antibody screening, inflammatory markers using the clinical lab, and immunological parameters such as CD40 Ligand expression and B lymphocyte subsets using flow cytometry. We will also apherese patients prestudy and identify antigen-specific B cells (that recognize specific cytokines) by flow cytometry and ELIspot. We will also perform a quality of life survey pre and post study and clinically score disease activity to evaluate for evidence of efficacy. This study has been written and passed through the NIH IRB. We have garnered support from Genetech who will provide drug for the study as well as PK and PD data, and search for human anti-chimeric antibodies (HACAs). We have not yet enrolled patients to this study as it has just been activated by Genentech this month (8/2013).

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Project End
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Budget End
Support Year
1
Fiscal Year
2013
Total Cost
$74,221
Indirect Cost
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Wu, Un-In; Holland, Steven M (2016) A genetic perspective on granulomatous diseases with an emphasis on mycobacterial infections. Semin Immunopathol 38:199-212
Ku, Cheng-Lung; Lin, Chia-Hao; Chang, Su-Wei et al. (2016) Anti-IFN-γ autoantibodies are strongly associated with HLA-DR*15:02/16:02 and HLA-DQ*05:01/05:02 across Southeast Asia. J Allergy Clin Immunol 137:945-8.e8
Gupta, Sarthak; Tatouli, Ioanna P; Rosen, Lindsey B et al. (2016) Distinct Functions of Autoantibodies Against Interferon in Systemic Lupus Erythematosus: A Comprehensive Analysis of Anticytokine Autoantibodies in Common Rheumatic Diseases. Arthritis Rheumatol 68:1677-87
Xie, Yingda L; Chen, Ray Y; Sereti, Irini et al. (2016) Reply to Tham et al. Clin Infect Dis 63:573-4
Xie, Yingda L; Rosen, Lindsey B; Sereti, Irini et al. (2016) Severe Paradoxical Reaction During Treatment of Disseminated Tuberculosis in a Patient With Neutralizing Anti-IFNγ Autoantibodies. Clin Infect Dis 62:770-3
Wu, Un-In; Holland, Steven M (2015) Host susceptibility to non-tuberculous mycobacterial infections. Lancet Infect Dis 15:968-80
Bayat, Ahmad; Burbelo, Peter D; Browne, Sarah K et al. (2015) Anti-cytokine autoantibodies in postherpetic neuralgia. J Transl Med 13:333
Burbelo, Peter D; Keller, Jason; Wagner, Jason et al. (2015) Serological diagnosis of pulmonary Mycobacterium tuberculosis infection by LIPS using a multiple antigen mixture. BMC Microbiol 15:205
Rosen, Lindsey B; Rocha Pereira, Nuno; Figueiredo, Cristóvão et al. (2015) Nocardia-induced granulocyte macrophage colony-stimulating factor is neutralized by autoantibodies in disseminated/extrapulmonary nocardiosis. Clin Infect Dis 60:1017-25
Martinez, Bianca; Browne, Sarah K (2014) Good syndrome, bad problem. Front Oncol 4:307

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