title: Circulating T cells to infliximab are detectable mainly in treated patients developing anti-drug antibodies and hypersensitivity reactions.
abstract: Antibodies recognizing infliximab (IFX) may develop in a proportion of treated patients, leading to loss of response or hypersensitivity reactions (HRs). T cell response to IFX has been poorly investigated. This paper was addressed to detect IFX-specific T cells in treated patients with inflammatory diseases developing, or not, anti-drug antibodies (ADA) and to correlate the presence of specific T cells with the clinical outcomes of the treatment. A co-culture system of IFX-loaded dendritic cells and purified autologous CD4+T cells was used to detect memory T cells in 32 ADA+and 39 ADA-IFX-treated patients and control groups. The cytokine profile of IFX-specific T cells was also studied in culture supernatants. IFX-specific cell proliferation was detected mainly in cells from ADA+patients, irrespective of their different diseases. HR patients displayed higher T cell proliferation than non-responder and tolerant patients. A mixed [interferon (IFN)-γ, interleukin (IL)-13, IL-10] cytokine profile was shown in cells from ADA+patients, while IL-10 was the most frequently detected cytokine in the supernatants of cultures from ADA- patients. Immunoglobulin (Ig)E+ADA+patients with previous HRs exhibited a more pronounced type 2 profile than IgE-ADA+patients. This work provides evidence that IFX-specific circulating T cells are detectable mainly in ADA+patients with HRs, regardless of their disease. The IFX-induced cytokine pattern partially correlates with the ADA isotype.
authors: Centre of Research DENOTHE and Department of Experimental and Clinical Medicine, University of Florence, Italy.|Immunoallergology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors: A
authors: A
authors: Vultaggio
authors: Centre of Research DENOTHE and Department of Experimental and Clinical Medicine, University of Florence, Italy.
authors: G
authors: G
authors: Petroni
authors: Centre of Research DENOTHE and Department of Experimental and Clinical Medicine, University of Florence, Italy.
authors: S
authors: S
authors: Pratesi
authors: Centre of Research DENOTHE and Department of Experimental and Clinical Medicine, University of Florence, Italy.
authors: F
authors: F
authors: Nencini
authors: Immunoallergology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors: D
authors: D
authors: Cammelli
authors: Gastroenterology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors: M
authors: M
authors: Milla
authors: Dermatology Clinic, Azienda Sanitaria Firenze, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
authors: F
authors: F
authors: Prignano
authors: Gastroenterology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors: V
authors: V
authors: Annese
authors: Centre of Research DENOTHE and Department of Experimental and Clinical Medicine, University of Florence, Italy.
authors: S
authors: S
authors: Romagnani
authors: Centre of Research DENOTHE and Department of Experimental and Clinical Medicine, University of Florence, Italy.
authors: E
authors: E
authors: Maggi
authors: Centre of Research DENOTHE and Department of Experimental and Clinical Medicine, University of Florence, Italy.|Immunoallergology Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
authors: A
authors: A
authors: Matucci
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000097:blood* / Q000276:immunology*; D005260:Female; D006801:Humans; D007154:Immune System Diseases / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D000069285:Infliximab / Q000009:adverse effects* / Q000627:therapeutic use; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines; D007518:Isoantibodies; D007073:Immunoglobulin E; D000069285:Infliximab
keywords: T cells; allergy; arthritis; cytokines