Background: Autophagy has emerged as a key mechanism in the survival and function of T and B lymphocytes, and its activation was involved in apoptosis resistance in rheumatoid arthritis (RA). To investigate whether the relationship between autophagy and apoptosis may impact the response to the therapy, we analyzed ex vivo spontaneous autophagy and apoptosis in patients with RA subjected to treatment with anti-tumor necrosis factor (TNF) drugs and in vitro the effects of TNFα and anti-TNF drugs on cell fate. Methods: Peripheral blood mononuclear cells (PBMCs) from 25 RA patients treated with anti-TNF drugs were analyzed for levels of autophagy marker LC3-II by western blot and for the percentage of annexin V-positive apoptotic cells by flow cytometry. The same techniques were used to assess autophagy and apoptosis after in vitro treatment with TNFα and etanercept in both PBMCs and fibroblast-like synoviocytes (FLS) from patients with RA. Results: PBMCs from patients with RA responsive to treatment showed a significant reduction in LC3-II levels, associated with an increased apoptotic activation after 4 months of therapy with anti-TNF drugs. Additionally, the expression of LC3-II correlated with DAS28. TNFα was able to induce autophagy in a dose-dependent manner after 24 h of culture in RA PBMCs and FLS. Moreover, etanercept caused a significant reduction of autophagy and of levels of citrullinated proteins. Conclusions: Our results show how the crosstalk between autophagy and apoptosis can sustain the survival of immune cells, thus influencing RA progression. This suggests that inhibition of autophagy represents a possible therapeutic target in RA.

Reduction of autophagy and increase in apoptosis correlates with a favorable clinical outcome in patients with rheumatoid arthritis treated with anti-TNF drugs / Vomero, M.; Manganelli, V.; Barbati, C.; Colasanti, T.; Capozzi, A.; Finucci, A.; Spinelli, F. R.; Ceccarelli, F.; Perricone, C.; Truglia, S.; Morrone, S.; Maggio, R.; Misasi, R.; Bombardieri, M.; Di Franco, M.; Conti, F.; Sorice, M.; Valesini, G.; Alessandri, C.. - In: ARTHRITIS RESEARCH & THERAPY. - ISSN 1478-6354. - 21:1(2019), p. 39. [10.1186/s13075-019-1818-x]

Reduction of autophagy and increase in apoptosis correlates with a favorable clinical outcome in patients with rheumatoid arthritis treated with anti-TNF drugs

Vomero, M.;Manganelli, V.;Barbati, C.
Membro del Collaboration Group
;
Colasanti, T.;Capozzi, A.
Membro del Collaboration Group
;
Finucci, A.;Spinelli, F. R.;Ceccarelli, F.
Membro del Collaboration Group
;
Truglia, S.;Morrone, S.;Misasi, R.;Di Franco, M.
Membro del Collaboration Group
;
Conti, F.
Membro del Collaboration Group
;
Sorice, M.
Membro del Collaboration Group
;
Valesini, G.;Alessandri, C.
Supervision
2019

Abstract

Background: Autophagy has emerged as a key mechanism in the survival and function of T and B lymphocytes, and its activation was involved in apoptosis resistance in rheumatoid arthritis (RA). To investigate whether the relationship between autophagy and apoptosis may impact the response to the therapy, we analyzed ex vivo spontaneous autophagy and apoptosis in patients with RA subjected to treatment with anti-tumor necrosis factor (TNF) drugs and in vitro the effects of TNFα and anti-TNF drugs on cell fate. Methods: Peripheral blood mononuclear cells (PBMCs) from 25 RA patients treated with anti-TNF drugs were analyzed for levels of autophagy marker LC3-II by western blot and for the percentage of annexin V-positive apoptotic cells by flow cytometry. The same techniques were used to assess autophagy and apoptosis after in vitro treatment with TNFα and etanercept in both PBMCs and fibroblast-like synoviocytes (FLS) from patients with RA. Results: PBMCs from patients with RA responsive to treatment showed a significant reduction in LC3-II levels, associated with an increased apoptotic activation after 4 months of therapy with anti-TNF drugs. Additionally, the expression of LC3-II correlated with DAS28. TNFα was able to induce autophagy in a dose-dependent manner after 24 h of culture in RA PBMCs and FLS. Moreover, etanercept caused a significant reduction of autophagy and of levels of citrullinated proteins. Conclusions: Our results show how the crosstalk between autophagy and apoptosis can sustain the survival of immune cells, thus influencing RA progression. This suggests that inhibition of autophagy represents a possible therapeutic target in RA.
2019
Apoptosis; Autophagy; Rheumatoid arthritis; TNF inhibitors; TNFα; Rheumatology; Immunology and Allergy; Immunology
01 Pubblicazione su rivista::01a Articolo in rivista
Reduction of autophagy and increase in apoptosis correlates with a favorable clinical outcome in patients with rheumatoid arthritis treated with anti-TNF drugs / Vomero, M.; Manganelli, V.; Barbati, C.; Colasanti, T.; Capozzi, A.; Finucci, A.; Spinelli, F. R.; Ceccarelli, F.; Perricone, C.; Truglia, S.; Morrone, S.; Maggio, R.; Misasi, R.; Bombardieri, M.; Di Franco, M.; Conti, F.; Sorice, M.; Valesini, G.; Alessandri, C.. - In: ARTHRITIS RESEARCH & THERAPY. - ISSN 1478-6354. - 21:1(2019), p. 39. [10.1186/s13075-019-1818-x]
File allegati a questo prodotto
File Dimensione Formato  
Vomero_Reduction_2019.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.44 MB
Formato Adobe PDF
1.44 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1235394
Citazioni
  • ???jsp.display-item.citation.pmc??? 22
  • Scopus 38
  • ???jsp.display-item.citation.isi??? 36
social impact