Baricitinib is a Janus kinase (JAK) 1 and 2 inhibitor approved for treating rheumatoid arthritis (RA). The JAK/STAT system is essential in the intracellular signaling of different cytokines and in the activation process of the monocyte lineage. This study verifies the effects of baricitinib on STAT phosphorylation in monocytes of RA patients and evaluates the correlation between STAT phosphorylation and response to therapy. We evaluated the disease activity of patients (DAS28CRP) at baseline (T0) and after 4 and 12 weeks (T1-T3) of treatment with baricitinib, dividing them into responders (n = 7) and non-responders (n = 7) based on the reduction of DAS28CRP between T0 and T1 of at least 1.2 points. Through flow cytometry, STAT1 phosphorylation was analyzed at T0/T1/T3 in monocytes, at basal conditions and after IL2, IFN alpha, and IL6 stimulation. We showed that monocyte frequency decreased from T0 to T1 only in responders. Regarding the phosphorylation of STAT1, we observed a tendency for higher basal pSTAT1 in monocytes of non-responder patients and, after 4 weeks, a significant reduction of cytokine-induced pSTAT1 in monocytes of responders compared with non-responders. The single IFN alpha stimulation only partially recapitulated the differences in STAT1 phosphorylation between the two patient subgroups. Finally, responders showed an increased IFN signature at baseline compared with non-responders. These results may suggest that monocyte frequency and STAT1 phosphorylation in circulating monocytes could represent early markers of response to baricitinib therapy.

Baricitinib therapy response in rheumatoid arthritis patients associates to STAT1 phosphorylation in monocytes / Tucci, G; Garufi, C; Pacella, I; Zagaglioni, M; Pinzon Grimaldos, A; Ceccarelli, F; Conti, F; Spinelli, Fr; Piconese, S. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 13:(2022). [10.3389/fimmu.2022.932240]

Baricitinib therapy response in rheumatoid arthritis patients associates to STAT1 phosphorylation in monocytes

Tucci, G;Garufi, C
Co-primo
;
Pacella, I;Pinzon Grimaldos, A;Ceccarelli, F;Conti, F;Spinelli, FR;Piconese, S
2022

Abstract

Baricitinib is a Janus kinase (JAK) 1 and 2 inhibitor approved for treating rheumatoid arthritis (RA). The JAK/STAT system is essential in the intracellular signaling of different cytokines and in the activation process of the monocyte lineage. This study verifies the effects of baricitinib on STAT phosphorylation in monocytes of RA patients and evaluates the correlation between STAT phosphorylation and response to therapy. We evaluated the disease activity of patients (DAS28CRP) at baseline (T0) and after 4 and 12 weeks (T1-T3) of treatment with baricitinib, dividing them into responders (n = 7) and non-responders (n = 7) based on the reduction of DAS28CRP between T0 and T1 of at least 1.2 points. Through flow cytometry, STAT1 phosphorylation was analyzed at T0/T1/T3 in monocytes, at basal conditions and after IL2, IFN alpha, and IL6 stimulation. We showed that monocyte frequency decreased from T0 to T1 only in responders. Regarding the phosphorylation of STAT1, we observed a tendency for higher basal pSTAT1 in monocytes of non-responder patients and, after 4 weeks, a significant reduction of cytokine-induced pSTAT1 in monocytes of responders compared with non-responders. The single IFN alpha stimulation only partially recapitulated the differences in STAT1 phosphorylation between the two patient subgroups. Finally, responders showed an increased IFN signature at baseline compared with non-responders. These results may suggest that monocyte frequency and STAT1 phosphorylation in circulating monocytes could represent early markers of response to baricitinib therapy.
2022
interferon; STAT; JAKi; monocytes; rheumatoid arthritis; ISGs
01 Pubblicazione su rivista::01a Articolo in rivista
Baricitinib therapy response in rheumatoid arthritis patients associates to STAT1 phosphorylation in monocytes / Tucci, G; Garufi, C; Pacella, I; Zagaglioni, M; Pinzon Grimaldos, A; Ceccarelli, F; Conti, F; Spinelli, Fr; Piconese, S. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 13:(2022). [10.3389/fimmu.2022.932240]
File allegati a questo prodotto
File Dimensione Formato  
Tucci_Baricitinib_2022.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 4.03 MB
Formato Adobe PDF
4.03 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/11573/1659889
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 6
social impact