Anti-TNF immunotherapy and tuberculosis reactivation: another mechanism revealed.
Anti-TNF immunotherapy has revolutionized the treatment of some inflammatory diseases, such as RA. However, a major concern is that patients receiving this therapy have an increased risk of fungal and bacterial infection, particularly of reactivating latent tuberculosis (TB). In this issue of the JCI, in an effort to understand how anti-TNF immunotherapy affects host mechanisms required to control TB, Bruns and colleagues examined the effects of the anti-TNF therapeutic infliximab on Mycobacterium tuberculosis-specific human lymphocytes (see the related article beginning on page 1167). The authors report that a granulysin-expressing CD45RA+ subset of effector memory CD8+ T cells that contributes to the killing of intracellular M. tuberculosis is depleted in vivo by infliximab in patients with RA, and that these cells are susceptible to complement-mediated lysis in the presence of infliximab in vitro. The study provides insight into host defense mechanisms that act to control TB infection and how they are affected during anti-TNF immunotherapy for autoimmune disease.
Miller
Elizabeth A
EA
Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
Ernst
Joel D
JD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects*; D000069285:Infliximab; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000209:etiology / Q000276:immunology* / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; C512779:SYTL4 protein, human; D014409:Tumor Necrosis Factor-alpha; D033921:Vesicular Transport Proteins; D054353:Perforin; D003165:Complement System Proteins; D000069285:Infliximab