A set of serum markers detecting systemic inflammation in psoriatic skin, entheseal, and joint disease in the absence of C-reactive protein and its link to clinical disease manifestations.


Journal

Arthritis research & therapy
ISSN: 1478-6362
Titre abrégé: Arthritis Res Ther
Pays: England
ID NLM: 101154438

Informations de publication

Date de publication:
12 02 2020
Historique:
received: 04 11 2019
accepted: 23 01 2020
entrez: 14 2 2020
pubmed: 14 2 2020
medline: 25 11 2020
Statut: epublish

Résumé

C-reactive protein (CRP) is often normal in patients with psoriatic disease. Herein, we aimed to define markers of systemic inflammation in patients with monomorphic and polymorphic psoriatic skin, entheseal, and joint disease. Three-step approach: (i) selection of serum markers elevated in psoriatic arthritis compared healthy controls from a panel of 10 different markers reflecting the pathophysiology of psoriatic disease; (ii) testing of these selected markers as well as C-reactive protein (CRP) in a larger cohort of 210 individuals- 105 healthy controls and 105 patients with psoriatic disease with either monomorphic skin (S), entheseal (E) or joint (A) involvement or polymorphic disease with various combinations of skin, entheseal and joint disease (SE, SA, EA, SEA); (iii) testing whether tumor necrosis factor (TNF) and interleukin (IL)-17 inhibitor therapy normalizes these markers. CRP was not elevated or was rarely elevated in the subgroups (S 0%, E 0%, A 20%, SE 7%, SA 33%, EA 27%, SEA 33%) despite active psoriatic disease. In sharp contrast, beta-defensin 2 and lipocalin-2 levels were elevated in the majority of patients with monomorphic skin (93% and 73%) and entheseal (both 53%), but not joint disease (27% and 20%). Conversely, elevations of calprotectin and IL-8 were found in the majority of patients with monomorphic joint disease (both 73%). IL-22 was elevated in all three monomorphic disease manifestations (S 60%, E 46%; A 60%). Furthermore, the vast majority of patients with polymorphic psoriatic disease (SE, SA, EA, SEA) showed widespread marker elevation. IL-17- and TNF inhibitor treatment significantly lowered all 5 markers of inflammation in PsA patients. Systemic inflammation is detectable in the majority of patients with psoriatic disease, even if CRP is normal. The respective marker pattern depends on the manifestation of psoriatic disease with respect to skin, entheseal, and joint involvement.

Sections du résumé

BACKGROUND
C-reactive protein (CRP) is often normal in patients with psoriatic disease. Herein, we aimed to define markers of systemic inflammation in patients with monomorphic and polymorphic psoriatic skin, entheseal, and joint disease.
METHODS
Three-step approach: (i) selection of serum markers elevated in psoriatic arthritis compared healthy controls from a panel of 10 different markers reflecting the pathophysiology of psoriatic disease; (ii) testing of these selected markers as well as C-reactive protein (CRP) in a larger cohort of 210 individuals- 105 healthy controls and 105 patients with psoriatic disease with either monomorphic skin (S), entheseal (E) or joint (A) involvement or polymorphic disease with various combinations of skin, entheseal and joint disease (SE, SA, EA, SEA); (iii) testing whether tumor necrosis factor (TNF) and interleukin (IL)-17 inhibitor therapy normalizes these markers.
RESULTS
CRP was not elevated or was rarely elevated in the subgroups (S 0%, E 0%, A 20%, SE 7%, SA 33%, EA 27%, SEA 33%) despite active psoriatic disease. In sharp contrast, beta-defensin 2 and lipocalin-2 levels were elevated in the majority of patients with monomorphic skin (93% and 73%) and entheseal (both 53%), but not joint disease (27% and 20%). Conversely, elevations of calprotectin and IL-8 were found in the majority of patients with monomorphic joint disease (both 73%). IL-22 was elevated in all three monomorphic disease manifestations (S 60%, E 46%; A 60%). Furthermore, the vast majority of patients with polymorphic psoriatic disease (SE, SA, EA, SEA) showed widespread marker elevation. IL-17- and TNF inhibitor treatment significantly lowered all 5 markers of inflammation in PsA patients.
CONCLUSIONS
Systemic inflammation is detectable in the majority of patients with psoriatic disease, even if CRP is normal. The respective marker pattern depends on the manifestation of psoriatic disease with respect to skin, entheseal, and joint involvement.

Identifiants

pubmed: 32051028
doi: 10.1186/s13075-020-2111-8
pii: 10.1186/s13075-020-2111-8
pmc: PMC7017480
doi:

Substances chimiques

Biomarkers 0
C-Reactive Protein 9007-41-4

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

26

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Auteurs

Maria V Sokolova (MV)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.
Deutsches Zentrum fur Immuntherapie (DZI), Erlangen, Germany.

David Simon (D)

Deutsches Zentrum fur Immuntherapie (DZI), Erlangen, Germany.
Division of Rheumatology and Immunology, Sakarya University School of Medicine, Sakarya, Turkey.

Kemal Nas (K)

Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China.

Mario M Zaiss (MM)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.
Deutsches Zentrum fur Immuntherapie (DZI), Erlangen, Germany.

Yubin Luo (Y)

Division of Rheumatology and Immunology, Sakarya University School of Medicine, Sakarya, Turkey.

Yi Zhao (Y)

Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China.

Jürgen Rech (J)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Germany.
Deutsches Zentrum fur Immuntherapie (DZI), Erlangen, Germany.

Georg Schett (G)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Germany. georg.schett@uk-erlangen.de.
Deutsches Zentrum fur Immuntherapie (DZI), Erlangen, Germany. georg.schett@uk-erlangen.de.

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Classifications MeSH