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The CD4+ Lymphopenic Sarcoidosis Phenotype Is Highly Responsive to Anti-Tumor Necrosis Factor-α Therapy

Elliott D. Crouser, MD; Gerard Lozanski, MD; Charity C. Fox, MD; David W. Hauswirth, MD; Rekha Raveendran, MD; Mark W. Julian, MS
Author and Funding Information

From the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine (Drs Crouser, Fox, and Hauswirth, and Mr Julian), Dorothy M. Davis Heart and Lung Research Institute; the Department of Medicine (Drs Crouser, Fox, Hauswirth, and Raveendran, and Mr Julian), and the Department of Pathology (Dr Lozanski), The Ohio State University Medical Center, Columbus, OH.

Correspondence to: Elliott D. Crouser, MD, 201 Davis Heart and Lung Research Institute, The Ohio State University Medical Center, 473 W 12th Ave, Columbus, OH 43210; e-mail: elliott.crouser@medctr.osu.edu


Presented in abstract form at the annual meeting of the American Thoracic Society in San Diego, CA, on May 17, 2009.

Funding/Support: This work was supported by a joint grant from the American Thoracic Society and Sarcoidosis Research Foundation.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;137(6):1432-1435. doi:10.1378/chest.09-2576
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The treatment options for patients with sarcoidosis are presently limited, and it is unclear which treatments are most effective for any given patient. We have identified a sarcoidosis phenotype characterized by CD4+ lymphopenia and resistance to conventional immunosuppressants, such as corticosteroids and methotrexate. Based on recent reports linking tumor necrosis factor (TNF)-α to regulatory T-cell (Treg) dysfunction, we hypothesized that sarcoidosis-associated CD4+ lymphopenia would resolve with anti-TNFα treatment. Five consecutive patients with CD4+ lymphopenia were treated with a chimeric anti-TNFα antibody (infliximab). Clinical disease manifestations and peripheral blood T-cell subsets were assessed before and after infliximab treatment. All patients experienced significant increases in absolute peripheral blood lymphocyte and CD4+ T-cell counts and demonstrated improvement in clinical disease manifestations in response to infliximab. No change in the distribution of T-cell subsets was noted. The presence of CD4+ lymphopenia identifies a distinct sarcoidosis phenotype that is particularly responsive to anti-TNFα therapy.


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