Deficient spontaneous in vitro apoptosis and increased tmTNF reverse signaling-induced apoptosis of monocytes predict suboptimal therapeutic response of rheumatoid arthritis to TNF inhibition

Arthritis Research & Therapy
Undine MeuschUlf Wagner

Abstract

In vitro apoptosis of peripheral monocytes in rheumatoid arthritis (RA) is disturbed and influenced by cytokine production and transmembrane TNF (tmTNF) reverse signaling. The goal of the study was the analysis of the predictive value of the rate of in vitro apoptosis for the therapeutic response to anti-TNF treatment. Spontaneous and tmTNF reverse signaling-induced apoptosis were determined in vitro in monocytes from 20 RA patients prior to initiation of therapeutic TNF inhibition with etanercept, and the subsequent clinical response was monitored. Spontaneous in vitro apoptosis was significantly reduced in RA patients compared to controls. Deficiency in spontaneous apoptosis was associated with an insufficient therapeutic response according to the European League Against Rheumatism (EULAR) response criteria and less reduction of the disease activity determined by disease activity score (DAS) 28. High susceptibility to reverse signaling-induced apoptosis was also associated with less efficient reduction in the DAS28. Of note, a strong negative correlation between the two apoptotic parameters was discernible, possibly indicative of two pathogenetically relevant processes counter-regulating each other. tmTNF reverse signaling in...Continue Reading

References

Jun 1, 1984·Annals of the Rheumatic Diseases·M M StevenC G Gemmell
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Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·L P Perera, T A Waldmann
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Citations

Sep 9, 2015·Zeitschrift für Rheumatologie·B StuhlmüllerT Häupl
Dec 17, 2017·Immunological Reviews·Martina MolgoraCecilia Garlanda
Oct 6, 2018·European Journal of Clinical Investigation·Jonas BystromRizgar A Mageed
Sep 2, 2019·Apoptosis : an International Journal on Programmed Cell Death·Baodi RenDan Liu

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Methods Mentioned

BETA
RSA
ESR

Software Mentioned

FlowJo
graphPad Prism

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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