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Article ; Online: Pain sensitisation and joint inflammation in patients with active rheumatoid arthritis.

Chaabo, Khaldoun / Chan, Estee / Garrood, Toby / Rutter-Locher, Zoe / Vincent, Alex / Galloway, James / Norton, Sam / Kirkham, Bruce W

RMD open

2024 Volume 10, Issue 1

Abstract: Introduction: Despite better therapies and strategies, many people with rheumatoid arthritis (RA) have persistent pain, often from abnormal pain processing, now termed nociplastic pain. However, RA patients with fibromyalgia (FM), a central nociplastic ... ...

Abstract	Introduction: Despite better therapies and strategies, many people with rheumatoid arthritis (RA) have persistent pain, often from abnormal pain processing, now termed nociplastic pain. However, RA patients with fibromyalgia (FM), a central nociplastic pain syndrome, also have power doppler ultrasound (PDUS+) joint inflammation. To understand the complex causes of pain, we performed clinical examination and patient-reported outcome measures (PROMs) plus comprehensive PDUS evaluation not previously combined. Methods: In a cross-sectional study of sequential RA patients with at least moderate DAS28 erythrocyte sedimentation rate disease activity, we assessed 66/68 joints for swelling and tenderness, respectively, FM American College of Rheumatology 2010 diagnostic criteria, completed PROMs for function, quality of life and mood, alongside PDUS examination of 44 joints. Statistical analysis included logistic regression modelling and regularised (lasso) logistic regression methods. Results: From 158 patients, 72 (46%) patients met FM criteria, with significantly worse tender joint counts and PROMs, but no differences in PDUS compared with the non-FM group. Categorising patients by PDUS+ joint presence and/or FM criteria, we identified four distinct groups: 43 (27.2%) patients with -FM-PD, 43 (27.2%) with -FM+PD, 42 (26.6%) with +FM-PD and 30 (19%) with +FM+PD. Both FM+ groups had worse PROMs for fatigue, mood and pain, compared with the FM- groups. We were unable to develop algorithms to identify different groups. Conclusion: The unexpected group -FM-PD group may have peripheral nociplastic pain, not commonly recognised in rheumatology. Only 46% of patients demonstrated PDUS+ inflammation. However clinical examination and PROMs did not reliably differentiate groups, emphasising PDUS remains an important tool.
MeSH term(s)	Humans ; Quality of Life ; Cross-Sectional Studies ; Arthritis, Rheumatoid/complications ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/drug therapy ; Pain/etiology ; Fibromyalgia/complications ; Fibromyalgia/diagnosis ; Inflammation
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2023-003784
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Article ; Online: A systematic review and meta-analysis of questionnaires to screen for pain sensitisation and neuropathic like pain in inflammatory arthritis.

Rutter-Locher, Zoe / Arumalla, Nikita / Norton, Sam / Taams, Leonie S / Kirkham, Bruce W / Bannister, Kirsty

Seminars in arthritis and rheumatism

2023 Volume 61, Page(s) 152207

Abstract: Background: Targeted pain relief is a major unmet medical need for patients with inflammatory arthritis (IA), where approximately 40% of patients experience persistent pain. Self-reported questionnaires which report on pain sensitivity and neuropathic ... ...

Abstract	Background: Targeted pain relief is a major unmet medical need for patients with inflammatory arthritis (IA), where approximately 40% of patients experience persistent pain. Self-reported questionnaires which report on pain sensitivity and neuropathic like pain may provide an insight into certain pain types to guide targeted treatment. Objective: In this systematic review and meta-analysis we evaluated self-reported pain sensitivity and neuropathic like pain in subjects with IA, as defined by questionnaires. Methods: MEDLINE, Embase, Web of Science, PsycINFO and google scholar were searched for publications and conference abstracts, reporting on pain sensitivity and neuropathic pain using painDETECT, DN4, LANSS, CSI, PSQ and McGill pain questionnaire in adult patients with IA. Risk of bias was assessed using National Institute of Health Quality Assessment Tool. Meta-analysis according to individual questionnaire criteria, was undertaken. Results: 63 studies (38 full text and 25 conference abstracts) were included in the review, reporting on a total of 13,035 patients. On meta-analysis, prevalence of pain sensitivity/neuropathic like pain in IA was 36% (95% CI 31-41%) according to painDETECT, 31% (95% CI 26-37%) according to the DN4, 40% (95% CI 32-49%) according to the LANSS and 42% (95% CI 34-51%) according to the CSI. On meta-regression, prevalence of pain sensitivity/neuropathic pain in RA was significantly lower than SpA (p = 0.01) and PsA (p = 0.002) using the painDETECT questionnaire. Across all questionnaires, pain sensitivity and neuropathic like pain were significantly associated with worse pain severity, disease activity, disability, quality of life and anxiety and depression measures. Studies reporting on whether neuropathic like pain is a predictor of treatment outcome were inconsistent. Conclusion: Pain sensitivity and neuropathic like pain contribute to pain perception in up to 42% of patients with IA. Despite substantial heterogeneity between studies on meta-analysis, this review highlights the large proportion of patients with IA who may experience pain due to underlying mechanisms other than, or in addition to, synovial inflammation.
MeSH term(s)	Adult ; Humans ; Quality of Life ; Arthritis, Psoriatic ; Neuralgia/diagnosis ; Neuralgia/etiology ; Surveys and Questionnaires ; Pain Measurement
Language	English
Publishing date	2023-04-26
Publishing country	United States
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	120247-9
ISSN	1532-866X ; 0049-0172
ISSN (online)	1532-866X
ISSN	0049-0172
DOI	10.1016/j.semarthrit.2023.152207
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Article ; Online: Human in vitro-induced IL-17A+ CD8+ T-cells exert pro-inflammatory effects on synovial fibroblasts.

Gray, Elizabeth H / Srenathan, Ushani / Durham, Lucy E / Lalnunhlimi, Sylvine / Steel, Kathryn J A / Catrina, Anca / Kirkham, Bruce W / Taams, Leonie S

Clinical and experimental immunology

2023 Volume 214, Issue 1, Page(s) 103–119

Abstract: IL-17A+ CD8+ T-cells, termed Tc17 cells, have been identified at sites of inflammation in several immune-mediated inflammatory diseases. However, the biological function of human IL-17A+ CD8+ T-cells is not well characterized, likely due in part to the ... ...

Abstract	IL-17A+ CD8+ T-cells, termed Tc17 cells, have been identified at sites of inflammation in several immune-mediated inflammatory diseases. However, the biological function of human IL-17A+ CD8+ T-cells is not well characterized, likely due in part to the relative scarcity of these cells. Here, we expanded IL-17A+ CD8+ T-cells from healthy donor PBMC or bulk CD8+ T-cell populations using an in vitro polarization protocol. We show that T-cell activation in the presence of IL-1β and IL-23 significantly increased the frequencies of IL-17A+ CD8+ T-cells, which was not further enhanced by IL-6, IL-2, or anti-IFNγ mAb addition. In vitro-generated IL-17A+ CD8+ T-cells displayed a distinct type-17 profile compared with IL-17A- CD8+ T-cells, as defined by transcriptional signature (IL17A, IL17F, RORC, RORA, MAF, IL23R, CCR6), high surface expression of CCR6 and CD161, and polyfunctional production of IL-17A, IL-17F, IL-22, IFNγ, TNFα, and GM-CSF. A significant proportion of in vitro-induced IL-17A+ CD8+ T-cells expressed TCRVα7.2 and bound MR1 tetramers indicative of MAIT cells, indicating that our protocol expanded both conventional and unconventional IL-17A+ CD8+ T-cells. Using an IL-17A secretion assay, we sorted the in vitro-generated IL-17A+ CD8+ T-cells for functional analysis. Both conventional and unconventional IL-17A+ CD8+ T-cells were able to induce pro-inflammatory IL-6 and IL-8 production by synovial fibroblasts from patients with psoriatic arthritis, which was reduced upon addition of anti-TNFα and anti-IL-17A neutralizing antibodies. Collectively, these data demonstrate that human in vitro-generated IL-17A+ CD8+ T-cells are biologically functional and that their pro-inflammatory function can be targeted, at least in vitro, using existing immunotherapy.
MeSH term(s)	Humans ; Interleukin-17 ; Interleukin-6/metabolism ; Leukocytes, Mononuclear/metabolism ; CD8-Positive T-Lymphocytes ; Tumor Necrosis Factor-alpha/metabolism ; Fibroblasts/metabolism
Chemical Substances	Interleukin-17 ; Interleukin-6 ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2023-06-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxad068
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Article ; Online: Drivers of Inflammation in Psoriatic Arthritis: the Old and the New.

O'Brien-Gore, Charlotte / Gray, Elizabeth H / Durham, Lucy E / Taams, Leonie S / Kirkham, Bruce W

Current rheumatology reports

2021 Volume 23, Issue 6, Page(s) 40

Abstract: Purpose of review: The recognition that IL-17 is produced by many lymphoid-like cells other than CD4+ T helper (Th17) cells raises the potential for new pathogenic pathways in IBD/psoriasis/SpA. We review recent knowledge concerning the role of ... ...

Abstract	Purpose of review: The recognition that IL-17 is produced by many lymphoid-like cells other than CD4+ T helper (Th17) cells raises the potential for new pathogenic pathways in IBD/psoriasis/SpA. We review recent knowledge concerning the role of unconventional and conventional lymphocytes expressing IL-17 in human PsA and axSpA. Recent findings: Innate-like lymphoid cells, namely gamma delta (γδ) T-cells, invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells, together with innate lymphoid cells (ILCs) are found at sites of disease in PsA/SpA. These cells are often skewed to Type-17 profiles and may significantly contribute to IL-17 production. Non-IL-23 dependent IL-17 production pathways, utilising cytokines such as IL-7 and IL-9, also characterise these cells. Both conventional CD4 and CD8 lymphocytes show pathogenic phenotypes at sites of disease. A variety of innate-like lymphoid cells and conventional lymphocytes contribute towards IL-17-mediated pathology in PsA/SpA. The responses of these cells to non-conventional immune and non-immune stimuli may explain characteristic clinical features of these diseases and potential therapeutic mechanisms of therapies such as Jak inhibitors.
MeSH term(s)	Arthritis, Psoriatic ; Cytokines/immunology ; Humans ; Immunity, Innate ; Inflammation ; Interleukin-17/immunology ; T-Lymphocyte Subsets/immunology
Chemical Substances	Cytokines ; Interleukin-17
Language	English
Publishing date	2021-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2057357-1
ISSN	1534-6307 ; 1523-3774
ISSN (online)	1534-6307
ISSN	1523-3774
DOI	10.1007/s11926-021-01005-x
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Article ; Online: Type 17-specific immune pathways are active in early spondyloarthritis.

Hughes, Catherine D / Ryan, Sarah E / Steel, Kathryn J A / van den Beukel, Michelle D / Trouw, L A / van Schie, Karin A J / Toes, René E M / Menon, Bina / Kirkham, Bruce W / Taams, Leonie S

RMD open

2023 Volume 9, Issue 4

Abstract: Objective: Undifferentiated, early inflammatory arthritis (EIA) can differentiate into seropositive or seronegative rheumatoid arthritis (RA), peripheral spondyloarthritis (SpA) or remain as seronegative undifferentiated inflammatory arthritis (UIA). ... ...

Abstract	Objective: Undifferentiated, early inflammatory arthritis (EIA) can differentiate into seropositive or seronegative rheumatoid arthritis (RA), peripheral spondyloarthritis (SpA) or remain as seronegative undifferentiated inflammatory arthritis (UIA). Little is known about immune pathways active in the early stages of SpA and seronegative UIA, in contrast to detailed knowledge of seropositive RA. The aim of this study was to examine if specific immune pathways were active in synovial CD4+ and CD8+ T cells in EIA. Methods: Synovial fluid (SF) samples from 30 patients with EIA were analysed for expression of IL-17A, IFNγ and TNFα in CD8+ or CD4+ T cells. Final clinical diagnoses were made at least 12 months after sample collection, by two independent clinicians blind to the study data. Results: Flow cytometry analysis of all EIA samples indicated considerable variation in synovial IL-17A+CD8+ T cells (Tc17) cell frequencies between patients. The group with a final diagnosis of SpA (psoriatic arthritis or peripheral SpA, n=14) showed a significant enrichment in the percentage of synovial Tc17 cells compared with the group later diagnosed with seronegative UIA (n=10). The small number of patients later diagnosed with seropositive RA (n=6) patients had few Tc17 cells, similar to our previous findings in established disease. In contrast, RA SF contained a significantly higher percentage of CD8+IFNγ+ T cells compared with SpA or seronegative UIA. Conclusion: These results suggest that adaptive T cell cytokine pathways differ not only between RA and SpA but also seronegative UIA early in the disease process, with a particular activation of Tc17 pathways in early SpA.
MeSH term(s)	Humans ; Interleukin-17 ; Synovial Fluid/metabolism ; Spondylarthritis/diagnosis ; Arthritis, Rheumatoid ; Arthritis, Psoriatic/metabolism
Chemical Substances	Interleukin-17
Language	English
Publishing date	2023-12-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2023-003328
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Article: A Comprehensive Review of Ixekizumab Efficacy in Nail Psoriasis from Clinical Trials for Moderate-to-Severe Psoriasis and Psoriatic Arthritis.

Kirkham, Bruce W / Egeberg, Alexander / Behrens, Frank / Pinter, Andreas / Merola, Joseph F / Holzkämper, Thorsten / Gallo, Gaia / Ng, Khai Jing / Bolce, Rebecca / Schuster, Christopher / Nash, Peter / Puig, Luis

Rheumatology and therapy

2023 Volume 10, Issue 5, Page(s) 1127–1146

Abstract: Nail psoriasis is a difficult-to-treat manifestation of psoriatic disease affecting up to 80% of patients with psoriatic arthritis (PsA) and 40-60% of patients with plaque psoriasis (PsO). Ixekizumab (IXE), a high-affinity monoclonal antibody that ... ...

Abstract	Nail psoriasis is a difficult-to-treat manifestation of psoriatic disease affecting up to 80% of patients with psoriatic arthritis (PsA) and 40-60% of patients with plaque psoriasis (PsO). Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of patients with PsA and patients with moderate-to-severe PsO. This narrative review aims to summarize nail psoriasis data generated from IXE clinical trials in patients with PsA (SPIRIT-P1, SPIRIT-P2, and SPIRIT-H2H) and/or moderate-to-severe PsO (UNCOVER-1, -2, -3, IXORA-R, IXORA-S, and IXORA-PEDS) with an emphasis on head-to-head clinical trial data. Across numerous trials explored, IXE treatment was associated with greater improvement in resolution of nail disease versus comparators at week 24, results which were maintained up to and beyond week 52. Additionally, patients experienced higher rates of resolution of nail disease versus comparators at week 24 and maintained high levels of resolution up to week 52 and beyond. In both PsA and PsO, IXE demonstrated efficacy in treating nail psoriasis, and therefore may be an effective therapy option. Trial Registration: ClinicalTrials.gov identifier UNCOVER-1 (NCT01474512), UNCOVER-2 (NCT01597245), UNCOVER-3 (NCT01646177), IXORA-PEDS (NCT03073200), IXORA-S (NCT02561806), IXORA-R (NCT03573323), SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295), SPIRIT-H2H (NCT03151551).
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2783278-8
ISSN	2198-6584 ; 2198-6576
ISSN (online)	2198-6584
ISSN	2198-6576
DOI	10.1007/s40744-023-00553-1
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Article ; Online: Psoriatic and rheumatoid arthritis joints differ in the composition of CD8+ tissue-resident memory T cell subsets.

Povoleri, Giovanni A M / Durham, Lucy E / Gray, Elizabeth H / Lalnunhlimi, Sylvine / Kannambath, Shichina / Pitcher, Michael J / Dhami, Pawan / Leeuw, Thomas / Ryan, Sarah E / Steel, Kathryn J A / Kirkham, Bruce W / Taams, Leonie S

Cell reports

2023 Volume 42, Issue 5, Page(s) 112514

Abstract: CD69+CD103+ tissue-resident memory T ( ... ...

Abstract	CD69+CD103+ tissue-resident memory T (T
MeSH term(s)	Humans ; Arthritis, Psoriatic/metabolism ; Memory T Cells ; T-Lymphocyte Subsets/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Arthritis, Rheumatoid/metabolism ; Immunologic Memory
Language	English
Publishing date	2023-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112514
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Article ; Online: The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies.

McGonagle, Dennis G / McInnes, Iain B / Kirkham, Bruce W / Sherlock, Jonathan / Moots, Robert

Annals of the rheumatic diseases

2019 Volume 78, Issue 9, Page(s) 1167–1178

Abstract: Although the pathogenic mechanisms underlying axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are not fully elucidated, several lines of evidence suggest that immune responses mediated by interleukin 17A (IL-17A) play a pivotal role in both ...

Abstract	Although the pathogenic mechanisms underlying axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are not fully elucidated, several lines of evidence suggest that immune responses mediated by interleukin 17A (IL-17A) play a pivotal role in both diseases. This is best highlighted by the significant clinical efficacy shown with inhibitors of IL-17A in treating axSpA and PsA. Nevertheless, a number of knowledge gaps exist regarding the role of IL-17A in the pathophysiology of spondyloarthritis in man, including its cellular origin, its precise role in discrete disease processes such enthesitis, bone erosion, and bone formation, and the reasons for the discrepant responses to IL-17A inhibition observed in certain other spondyloarthritis manifestations. In this review, we focus on the latest data from studies investigating the role of IL-17A in ankylosing spondylitis (AS) and PsA that build on existing and emerging scientific knowledge in the field. Key remaining research questions are also highlighted to guide future research.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Arthritis, Psoriatic/drug therapy ; Arthritis, Psoriatic/metabolism ; Biomarkers/metabolism ; Humans ; Interleukin-17/antagonists & inhibitors ; Interleukin-17/physiology ; Spondylarthritis/drug therapy ; Spondylarthritis/metabolism
Chemical Substances	Antibodies, Monoclonal, Humanized ; Biomarkers ; IL17A protein, human ; Interleukin-17 ; secukinumab (DLG4EML025)
Language	English
Publishing date	2019-07-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	7090-7
ISSN	1468-2060 ; 0003-4967
ISSN (online)	1468-2060
ISSN	0003-4967
DOI	10.1136/annrheumdis-2019-215356
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Article ; Online: Optimising psoriatic arthritis therapy with immunological methods to increase standard evaluation: the protocol of an open-label multicentre, parallel-group, two-arm randomised controlled study evaluation precision medicine approach in the treatment of psoriatic arthritis.

Ooms, Alexander / Al-Mossawi, Hussein / Bennett, Louise / Bogale, Mimi / Bowness, Paul / Francis, Anne / Goodyear, Carl / Kirkham, Bruce W / Lalnunhlimi, Sylvine / McInnes, Iain B / Richards, Duncan / Siebert, Stefan / Taams, Leonie S / Tulunay Virlan, Aysin / Yager, Nicole / Coates, Laura C

BMJ open

2023 Volume 13, Issue 9, Page(s) e078539

Abstract: Introduction: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients ... ...

Abstract	Introduction: Psoriatic arthritis (PsA) affects around 150 000 people in the UK of whom around 50% require treatment with biologics. The most used biologics for PsA target tumour necrosis factor (TNF) or interleukin-17A (IL-17A). About 50% of patients respond to each, but it is not currently possible to predict response for individual patients, necessitating sequential treatment steps. A recent proof of concept study in PsA suggested that using peripheral immunophenotype to choose therapy could improve time to treatment response.This study will test the hypothesis, within an open-label parallel-group biomarker-stratified multicentre randomised controlled trial, which the baseline proportion of CD4+T cells with an activated type 17 immunophenotype (Th17 levels) predicts response to IL-17A or TNF inhibitors in PsA. Additional analyses will identify if the model can be refined by combining additional clinical and immunophenotypic factors. Statistical modelling will be used to predict the likely effectiveness of these approaches compared with standard care. Methods and analysis: Patients with PsA eligible to start their first biologic as part of standard care are recruited and baseline blood tests are taken for immunophenotyping. Participants are stratified equally by Th17 levels and randomised 1:1 to receive either TNF (adalimumab) or IL-17A (secukinumab) inhibitors. The primary analysis will establish the interaction between baseline immunophenotype and treatment on the primary outcome (achievement of minimal disease activity criteria at week 24). In secondary analysis, modelling will identify if this prediction model can be optimised further by incorporating clinical phenotypes and additional immunophenotyping techniques. Ethics and dissemination: Ethical approval for the study was granted by the North West Preston Research Ethics Committee (ref 21/NW/0016). Dissemination will be via conference presentations and peer-reviewed publications, aiming to impact on treatment guidelines. Trial registration number: ISRCTN17228602.
MeSH term(s)	Humans ; Arthritis, Psoriatic/drug therapy ; Arthritis, Psoriatic/pathology ; Antirheumatic Agents/therapeutic use ; Interleukin-17/therapeutic use ; Precision Medicine ; Biological Products/therapeutic use ; Treatment Outcome ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic
Chemical Substances	Antirheumatic Agents ; Interleukin-17 ; Biological Products
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-078539
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Article ; Online: IL-17 in the immunopathogenesis of spondyloarthritis.

Taams, Leonie S / Steel, Kathryn J A / Srenathan, Ushani / Burns, Lachrissa A / Kirkham, Bruce W

Nature reviews. Rheumatology

2018 Volume 14, Issue 8, Page(s) 453–466

Abstract: Spondyloarthritis (SpA) is a term that refers to a group of inflammatory diseases that includes psoriatic arthritis, axial SpA and nonradiographic axial SpA, reactive arthritis, enteropathic arthritis and undifferentiated SpA. The disease subtypes share ... ...

Abstract	Spondyloarthritis (SpA) is a term that refers to a group of inflammatory diseases that includes psoriatic arthritis, axial SpA and nonradiographic axial SpA, reactive arthritis, enteropathic arthritis and undifferentiated SpA. The disease subtypes share clinical and immunological features, including joint inflammation (peripheral and axial skeleton); skin, gut and eye manifestations; and the absence of diagnostic autoantibodies (seronegative). The diseases also share genetic factors. The aetiology of SpA is still the subject of research by many groups worldwide. Evidence from genetic, experimental and clinical studies has accumulated to indicate a clear role for the IL-17 pathway in the pathogenesis of SpA. The IL-17 family consists of IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F, of which IL-17A is the best studied. IL-17A is a pro-inflammatory cytokine that also has the capacity to promote angiogenesis and osteoclastogenesis. Of the six family members, IL-17A has the strongest homology with IL-17F. In this Review, we discuss how IL-17A and IL-17F and their cellular sources might contribute to the immunopathology of SpA.
MeSH term(s)	Animals ; Antirheumatic Agents/pharmacology ; Antirheumatic Agents/therapeutic use ; CD8-Positive T-Lymphocytes/immunology ; Gene Expression Regulation/drug effects ; Genetic Testing ; Humans ; Interleukin-17/genetics ; Interleukin-17/metabolism ; Interleukin-23/metabolism ; Signal Transduction/drug effects ; Spondylarthritis/drug therapy ; Spondylarthritis/genetics ; Spondylarthritis/immunology
Chemical Substances	Antirheumatic Agents ; IL17A protein, human ; IL17F protein, human ; Interleukin-17 ; Interleukin-23
Language	English
Publishing date	2018-07-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2491532-4
ISSN	1759-4804 ; 1759-4790
ISSN (online)	1759-4804
ISSN	1759-4790
DOI	10.1038/s41584-018-0044-2
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