Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

IL-40: A New B Cell-Associated Cytokine Up-Regulated in Rheumatoid Arthritis Decreases Following the Rituximab Therapy and Correlates With Disease Activity, Autoantibodies, and NETosis

A. Navrátilová, L. Andrés Cerezo, H. Hulejová, V. Bečvář, M. Tomčík, M. Komarc, D. Veigl, D. Tegzová, J. Závada, M. Olejárová, K. Pavelka, J. Vencovský, L. Šenolt

. 2021 ; 12 (-) : 745523. [pub] 20211021

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22012074

Background: Interleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated the function of IL-40 in rheumatoid arthritis (RA). Methods: IL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined. Results: IL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (p<0.0001). Similarly, IL-40 was increased in the serum of RA patients compared to HC, OA, or SLE (p<0.0001 for all) and decreased after 16 and 24 weeks (p<0.01 and p<0.01) following rituximab treatment. No significant effect of adalimumab on IL-40 was observed. IL-40 levels in RA patients correlated with rheumatoid factor-IgM and anti-cyclic citrullinated peptides (anti-CCP) in the serum (p<0.0001 and p<0.01), as well as in the synovial fluid (p<0.0001 and p<0.001). Synovial fluid IL-40 was also associated with disease activity score DAS28 (p<0.05), synovial fluid leukocyte count (p<0.01), neutrophil attractants IL-8 (p<0.01), MIP-1α (p<0.01), and markers of neutrophil extracellular traps externalization (NETosis) such as proteinase 3 (p<0.0001) and neutrophil elastase (p<0.0001). Synovial fibroblasts exposed to IL-40 increased the secretion of IL-8 (p<0.01), MCP-1 (p<0.05), and MMP-13 (p<0.01) compared to the unstimulated cells. Conclusions: We show the up-regulation of IL-40 in RA and its decrease following B cell depleting therapy. The association of IL-40 with autoantibodies, chemokines, and markers of NETosis may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 in synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22012074
003      
CZ-PrNML
005      
20220506131106.0
007      
ta
008      
220425s2021 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3389/fimmu.2021.745523 $2 doi
035    __
$a (PubMed)34745117
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Navrátilová, Adela $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia
245    10
$a IL-40: A New B Cell-Associated Cytokine Up-Regulated in Rheumatoid Arthritis Decreases Following the Rituximab Therapy and Correlates With Disease Activity, Autoantibodies, and NETosis / $c A. Navrátilová, L. Andrés Cerezo, H. Hulejová, V. Bečvář, M. Tomčík, M. Komarc, D. Veigl, D. Tegzová, J. Závada, M. Olejárová, K. Pavelka, J. Vencovský, L. Šenolt
520    9_
$a Background: Interleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated the function of IL-40 in rheumatoid arthritis (RA). Methods: IL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined. Results: IL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (p<0.0001). Similarly, IL-40 was increased in the serum of RA patients compared to HC, OA, or SLE (p<0.0001 for all) and decreased after 16 and 24 weeks (p<0.01 and p<0.01) following rituximab treatment. No significant effect of adalimumab on IL-40 was observed. IL-40 levels in RA patients correlated with rheumatoid factor-IgM and anti-cyclic citrullinated peptides (anti-CCP) in the serum (p<0.0001 and p<0.01), as well as in the synovial fluid (p<0.0001 and p<0.001). Synovial fluid IL-40 was also associated with disease activity score DAS28 (p<0.05), synovial fluid leukocyte count (p<0.01), neutrophil attractants IL-8 (p<0.01), MIP-1α (p<0.01), and markers of neutrophil extracellular traps externalization (NETosis) such as proteinase 3 (p<0.0001) and neutrophil elastase (p<0.0001). Synovial fibroblasts exposed to IL-40 increased the secretion of IL-8 (p<0.01), MCP-1 (p<0.05), and MMP-13 (p<0.01) compared to the unstimulated cells. Conclusions: We show the up-regulation of IL-40 in RA and its decrease following B cell depleting therapy. The association of IL-40 with autoantibodies, chemokines, and markers of NETosis may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 in synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.
650    _2
$a adalimumab $x terapeutické užití $7 D000068879
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a revmatoidní artritida $x genetika $x imunologie $x metabolismus $7 D001172
650    _2
$a autoprotilátky $x krev $7 D001323
650    _2
$a B-lymfocyty $x účinky léků $x imunologie $7 D001402
650    _2
$a biologické markery $7 D015415
650    _2
$a kultivované buňky $7 D002478
650    _2
$a kohortové studie $7 D015331
650    _2
$a cytokiny $x analýza $7 D016207
650    _2
$a extracelulární pasti $x imunologie $7 D065206
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a fibroblasty $7 D005347
650    _2
$a regulace genové exprese $x účinky léků $7 D005786
650    _2
$a lidé $7 D006801
650    _2
$a systémový lupus erythematodes $x imunologie $x metabolismus $7 D008180
650    _2
$a lymfocytární deplece $7 D008212
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a matrixová metaloproteinasa 13 $x analýza $7 D053509
650    _2
$a lidé středního věku $7 D008875
650    _2
$a artróza kolenních kloubů $x imunologie $x metabolismus $7 D020370
650    _2
$a rituximab $x farmakologie $x terapeutické užití $7 D000069283
650    _2
$a synoviální tekutina $x chemie $x imunologie $7 D013582
650    _2
$a synoviální membrána $x chemie $x imunologie $7 D013583
650    _2
$a TNF-alfa $x antagonisté a inhibitory $7 D014409
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Andrés Cerezo, Lucie $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia
700    1_
$a Hulejová, Hana $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia
700    1_
$a Bečvář, Viktor $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia
700    1_
$a Tomčík, Michal $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia
700    1_
$a Komarc, Martin $u Department of Methodology, Faculty of Physical Education and Sport, Charles University, Prague, Czechia
700    1_
$a Veigl, David $u First Orthopaedic Clinic, 1st Faculty of Medicine, Charles University, Prague, Czechia
700    1_
$a Tegzová, Dana $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia
700    1_
$a Závada, Jakub $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia
700    1_
$a Olejárová, Marta $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia
700    1_
$a Pavelka, Karel $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia
700    1_
$a Vencovský, Jiří $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia
700    1_
$a Šenolt, Ladislav $u Department of Experimental Rheumatology, Institute of Rheumatology, Prague, Czechia $u Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czechia
773    0_
$w MED00181405 $t Frontiers in immunology $x 1664-3224 $g Roč. 12, č. - (2021), s. 745523
856    41
$u https://pubmed.ncbi.nlm.nih.gov/34745117 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20220425 $b ABA008
991    __
$a 20220506131058 $b ABA008
999    __
$a ok $b bmc $g 1789600 $s 1163275
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 12 $c - $d 745523 $e 20211021 $i 1664-3224 $m Frontiers in immunology $n Front Immunol $x MED00181405
LZP    __
$a Pubmed-20220425
Zpět

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace