The CD4+ lymphopenic sarcoidosis phenotype is highly responsive to anti-tumor necrosis factor-{alpha} therapy.
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)-alpha to regulatory T-cell (Treg) dysfunction, we hypothesized that sarcoidosis-associated CD4(+) lymphopenia would resolve with anti-TNFalpha treatment. Five consecutive patients with CD4(+) lymphopenia were treated with a chimeric anti-TNFalpha 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-TNFalpha therapy.
Crouser
Elliott D
ED
201 Davis Heart and Lung Research Institute, The Ohio State University Medical Center, 473 W 12th Ave, Columbus, OH 43210, USA. elliott.crouser@medctr.osu.edu
Lozanski
Gerard
G
Fox
Charity C
CC
Hauswirth
David W
DW
Raveendran
Rekha
R
Julian
Mark W
MW
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000188:drug therapy* / Q000276:immunology; D010641:Phenotype; D012507:Sarcoidosis / Q000188:drug therapy* / Q000276:immunology; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000069285:Infliximab