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TLR1/2 and 5 induce elevated cytokine levels from rheumatoid arthritis monocytes independent of ACPA or RF autoantibody status

TLR1/2 and 5 induce elevated cytokine levels from rheumatoid arthritis monocytes independent of ACPA or RF autoantibody status
TLR1/2 and 5 induce elevated cytokine levels from rheumatoid arthritis monocytes independent of ACPA or RF autoantibody status
Objective: Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease. Both rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are associated with more progressive disease and higher levels of systemic inflammation. Monocyte activation of toll-like receptors (TLRs) by endogenous ligands is a potential source of increased production of systemic cytokines. RA monocytes have elevated TLRs, some of which are associated with the disease activity score using 28 joints (DAS28). The aim of this study was to measure TLR-induced cytokine production from monocytes, stratified by autoantibody status, to assess if their capacity to induce cytokines is related to autoantibody status or DAS28.

Methods: Peripheral blood monocytes isolated from RA patients and healthy controls were stimulated with TLR1/2, TLR2/6, TLR4, TLR5, TLR7, TLR8 and TLR9 ligands for 18 hours before measuring interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα) and IL-10. Serum was used to confirm the autoantibody status. Cytokine levels were compared with RF, ACPA and DAS28.

Results: RA monocytes demonstrated significantly increased IL-6 and TNFα upon TLR1/2 stimulation and IL-6 and IL-10 upon TLR5 activation. TLR7 and TLR9 activation did not induce cytokines and no significant differences were observed between RA and healthy control monocytes upon TLR2/6, TLR4 or TLR8 activation. When stratified by ACPA or RF status there were no correlations between autoantibody status and elevated cytokine levels. However, TLR1/2-induced IL-6 did correlate with DAS28.

Conclusions: Elevated TLR-induced cytokines in RA monocytes were not related to ACPA or RF status. However, TLR1/2-induced IL-6 was associated with disease activity.
1462-0324
3533–3539
Thwaites, R.S
bf3c492b-f939-4066-b3e1-0a3f3a66bdd6
Unterberger, S.
3ba48a52-7692-4f3d-adb5-e354afb7dbf4
Chamberlain, G.
162cc10b-6840-47be-aa44-84ee776b784b
Walker-Bone, K.
ad7d1336-ed2c-4f39-ade5-da84eb412109
Davies, K.A.
f403cf7f-7a51-4523-aab5-0991e1fb5c23
Sacre, S.
b71cc07c-d081-4c6f-b2f7-cdac7b7bb94b
Thwaites, R.S
bf3c492b-f939-4066-b3e1-0a3f3a66bdd6
Unterberger, S.
3ba48a52-7692-4f3d-adb5-e354afb7dbf4
Chamberlain, G.
162cc10b-6840-47be-aa44-84ee776b784b
Walker-Bone, K.
ad7d1336-ed2c-4f39-ade5-da84eb412109
Davies, K.A.
f403cf7f-7a51-4523-aab5-0991e1fb5c23
Sacre, S.
b71cc07c-d081-4c6f-b2f7-cdac7b7bb94b

Thwaites, R.S, Unterberger, S., Chamberlain, G., Walker-Bone, K., Davies, K.A. and Sacre, S. (2020) TLR1/2 and 5 induce elevated cytokine levels from rheumatoid arthritis monocytes independent of ACPA or RF autoantibody status. Rheumatology, 59 (11), 3533–3539. (doi:10.1093/rheumatology/keaa220).

Record type: Article

Abstract

Objective: Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease. Both rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) are associated with more progressive disease and higher levels of systemic inflammation. Monocyte activation of toll-like receptors (TLRs) by endogenous ligands is a potential source of increased production of systemic cytokines. RA monocytes have elevated TLRs, some of which are associated with the disease activity score using 28 joints (DAS28). The aim of this study was to measure TLR-induced cytokine production from monocytes, stratified by autoantibody status, to assess if their capacity to induce cytokines is related to autoantibody status or DAS28.

Methods: Peripheral blood monocytes isolated from RA patients and healthy controls were stimulated with TLR1/2, TLR2/6, TLR4, TLR5, TLR7, TLR8 and TLR9 ligands for 18 hours before measuring interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα) and IL-10. Serum was used to confirm the autoantibody status. Cytokine levels were compared with RF, ACPA and DAS28.

Results: RA monocytes demonstrated significantly increased IL-6 and TNFα upon TLR1/2 stimulation and IL-6 and IL-10 upon TLR5 activation. TLR7 and TLR9 activation did not induce cytokines and no significant differences were observed between RA and healthy control monocytes upon TLR2/6, TLR4 or TLR8 activation. When stratified by ACPA or RF status there were no correlations between autoantibody status and elevated cytokine levels. However, TLR1/2-induced IL-6 did correlate with DAS28.

Conclusions: Elevated TLR-induced cytokines in RA monocytes were not related to ACPA or RF status. However, TLR1/2-induced IL-6 was associated with disease activity.

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Accepted/In Press date: 30 March 2020
e-pub ahead of print date: 28 June 2020
Published date: November 2020

Identifiers

Local EPrints ID: 439122
URI: http://eprints.soton.ac.uk/id/eprint/439122
ISSN: 1462-0324
PURE UUID: 55c87320-7095-44dc-a1b6-a4063ea5b202
ORCID for K. Walker-Bone: ORCID iD orcid.org/0000-0002-5992-1459

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Date deposited: 03 Apr 2020 16:31
Last modified: 17 Mar 2024 05:27

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Contributors

Author: R.S Thwaites
Author: S. Unterberger
Author: G. Chamberlain
Author: K. Walker-Bone ORCID iD
Author: K.A. Davies
Author: S. Sacre

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