Interleukin-34 in the Serum and Synovial Fluid of Rheumatoid Arthritis Patients: Relation to Disease Activity and Radiographic Damage

Zahraa I. Selim; Sonya M. Rashad; Marwa Mahmoud Abdelaziz; Shaimaa Salah; Doaa Mohammad Fouad; Helal F. Hetta

doi:10.1055/a-0606-4982

Aktuelle Rheumatologie, Inhaltsverzeichnis

Aktuelle Rheumatologie 2019; 44(01): 65-70
DOI: 10.1055/a-0606-4982

Originalarbeit

Interleukin-34 in the Serum and Synovial Fluid of Rheumatoid Arthritis Patients: Relation to Disease Activity and Radiographic Damage

Interleukin-34 in Serum und Synovialflüssigkeit von Patienten mit rheumatoider Arthritis: Beziehung zu Krankheitsaktivität und radiologischer Schädigung

Zahraa I. Selim

¹Rheumatology and Rehabilitation Department, Faculty of Medicine, Assiut University, Assiut, Egypt

,

Sonya M. Rashad

¹Rheumatology and Rehabilitation Department, Faculty of Medicine, Assiut University, Assiut, Egypt

,

Marwa Mahmoud Abdelaziz

¹Rheumatology and Rehabilitation Department, Faculty of Medicine, Assiut University, Assiut, Egypt

,

Shaimaa Salah

¹Rheumatology and Rehabilitation Department, Faculty of Medicine, Assiut University, Assiut, Egypt

,

Doaa Mohammad Fouad

²Radiology Department, South Egypt cancer institute

,

Helal F. Hetta

³Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt

› Institutsangaben

Abstract

Background Interleukin 34 (IL-34) is a recently discovered proinflammatory cytokine that can promote inflammation and osteoclastogenesis in arthritic joints. In this study, we tried to assess the serum and synovial fluid (SF) levels of IL-34 in rheumatoid arthritis (RA) patients, and to determine its relationship with disease activity and radiographic damage.

Patients and methods ELISA was used to evaluate IL-34 levels in the serum of RA patients (n=50), osteoarthritis (OA) patients (n=28), and healthy control subjects (n=20) and in SF isolated from RA and OA patients. Disease activity in RA patients was assessed using the disease activity score-28 (DAS 28). The extent of radiographic joint damage, narrowing, and erosions was assessed.

Results Serum IL-34 level was significantly elevated in RA patients compared to that in OA patients and healthy controls (P<0.0001). Synovial IL-34 level was also significantly elevated in RA patients compared to that in OA patients (P=0.0004). Serum and synovial IL-34 levels were significantly higher in cases that were rheumatoid factor (RF) positive (n=28) compared to the levels in RF-negative RA cases (n=22) (P=0.03 and P=0.04, respectively). Serum and synovial IL-34 levels were positively correlated with RF (r=0.43, P=0.02 and r=0.39, P=0.03, respectively), and with the extent of radiological damage (SENS) (P=0.0002 and P<0.0001, respectively). However, no significant correlation between IL-34 levels and disease activity was found.

Conclusion IL-34 appears to play a key role in the pathogenesis of RA and contribute to bone destruction, making it a potential therapeutic target in the management armamentarium of the disease.

Zusammenfassung

Hintergrund Interleukin 34 (IL-34) ist ein vor Kurzem entdecktes proinflammatorisches Zytokin, das die Entzündung und die Osteoklastogenese in arthritischen Gelenken begünstigen kann. In dieser Studie wurde versucht, die IL-34-Spiegel von Patienten mit rheumatoider Arthritis (RA) in Serum und Synovialflüssigkeit (SF) zu bestimmen und deren Beziehung zu Krankheitsaktivität und radiologischen Schäden zu ermitteln.

Patienten und Methoden Mithilfe eines ELISA-Assays untersuchten wir die IL-34-Spiegel im Serum von RA-Patienten (n=50), Patienten mit Arthrose (Osteoarthritis, OA) (n=28) und gesunden Kontrollprobanden (n=20) sowie in der von RA- und OA-Patienten isolierten SF. Mithilfe des Disease Activity Score-28 (DAS 28) wurde die Krankheitsaktivität bei RA-Patienten bestimmt. Ferner wurde das Ausmaß radiologischer Gelenkschäden, Einengungen und Erosionen beurteilt.

Ergebnisse Der Serum-IL-34-Spiegel war bei den RA-Patienten im Vergleich zu OA-Patienten und gesunden Probanden signifikant erhöht (p<0,0001). Ebenso fand sich eine signifikante Erhöhung des synovialen IL-34-Spiegels bei den RA-Patienten im Vergleich zu den OA-Patienten (p=0,0004). Die IL-34-Spiegel in Serum und Synovialflüssigkeit waren bei Rheumafaktor(RF)-positiven Patienten (n=28) signifikant höher als bei RF-negativen RA-Patienten (n=22) (p=0,03 bzw. p=0,04). Die IL-34-Spiegel in Serum und Synovialflüssigkeit korrelierten positiv mit dem RF (r=0,43; p=0,02 bzw. r=0,39; p=0,03) und mit dem Ausmaß der radiologischen Schädigung (SENS) (p=0,0002 bzw. p<0,0001). Allerdings zeigte sich keine signifikante Korrelation zwischen den IL-34-Spiegeln und der Krankheitsaktivität.

Schlussfolgerung IL-34 scheint eine wichtige Rolle bei der Pathogenese von RA zu spielen und zur Osteodestruktion beizutragen. Daher ist IL-34 ein potenzielles therapeutisches Angriffsziel im Behandlungsinstrumentarium der Erkrankung.

Key words

Interleukin-34 - Rheumatoid arthritis - DAS-28 - radiographic damage

Schlüsselwörter

Rheumatoide Arthritis - Arthrose - radiologische Schäden

Volltext

Referenzen

References
1 Hayashi K, Satoi K, Sato-Mito N. et al. Nutritional status in relation to adipokines and oxidative stress is associated with disease activity in patients with rheumatoid arthritis. Nutrition 2012; 28: 1109-1114
2 Al-Saadany HM, Hussein MS, Gaber RA. et al. Th-17 cells and serum IL-17 in rheumatoid arthritis patients: Correlation with disease activity and severity. Egyptian Rheumatologist 2015 6
3 Gheita TA, Azkalany GS, Gaber W et al. Clinical significance of serum TNFa and-308 G/A promoter polymorphism in rheumatoid arthritis. Egyptian Rheumatologist 2014; 37: doi:10.1016/j.ejr.2014.07.001
4 Helal AMH, Shahine EM, Hassan MM. et al. Fatigue in rheumatoid arthritis and its relation to interleukin-6 serum level. The Egyptian Rheumatologist 2012; 34: 153-157
5 Korayem HK, Rezk MM, Hassan MM. et al. Relation between serum IL-17 level and risk of osteoporotic fracture in premenopausal rheumatoid arthritis patients: Clinical, radiological and laboratory studies. The Egyptian Rheumatologist 2016; 38: 85-90
6 Abdel-Wahab SM, Tharwat I, Atta DS. et al. Serum level of interleukin-33 in rheumatoid arthritis patients and its association with bone erosion and interstitial lung disease. The Egyptian Rheumatologist 2016; 38: 99-104
7 Redlich K, Hayer S, Ricci R. et al. Osteoclasts are essential for TNF-α–mediated joint destruction. The Journal of clinical investigation 2002; 110: 1419
8 Pettit AR, Ji H, von Stechow D. et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. The American journal of pathology 2001; 159: 1689-1699
9 Takayanagi H. Osteoimmunology: Shared mechanisms and crosstalk between the immune and bone systems. Nature Reviews Immunology 2007; 7: 292-304
10 Danks L, Sabokbar A, Gundle R. et al. Synovial macrophage-osteoclast differentiation in inflammatory arthritis. Annals of the rheumatic diseases 2002; 61: 916-921
11 Lin H, Lee E, Hestir K. et al. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 2008; 320: 807-811
12 Chen Z, Buki K, Vääräniemi J. et al. The critical role of IL-34 in osteoclastogenesis. PloS one 2011; 6: e18689
13 Baud'Huin M, Renault R, Charrier C. et al. Interleukin -34 is expressed by giant cell tumours of bone and plays a key role in RANKL-induced osteoclastogenesis. The Journal of pathology 2010; 221: 77-86
14 Chemel M, Le Goff BI, Brion R et al. Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients. Annals of the rheumatic diseases 2011 p. annrheumdis-2011-200096
15 Hwang S-J, Choi B, Kang S-S. et al. Interleukin-34 produced by human fibroblast-like synovial cells in rheumatoid arthritis supports osteoclastogenesis. Arthritis research & therapy 2012; 14: R14
16 Eda H, Zhang J, Keith RH. et al. Macrophage-colony stimulating factor and interleukin-34 induce chemokines in human whole blood. Cytokine 2010; 52: 215-220
17 Tian Y, Shen H, Xia L. et al. Elevated serum and synovial fluid levels of interleukin-34 in rheumatoid arthritis: Possible association with disease progression via interleukin-17 production. Journal of Interferon & Cytokine Research 2013; 33: 398-401
18 Aletaha D, Neogi T, Silman AJ. et al. Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis & Rheumatology 2010; 62: 2569-2581
19 Zhang W, Doherty M, Peat G. et al. EULAR evidence based recommendations for the diagnosis of knee osteoarthritis. Annals of the rheumatic diseases 2009; 69
20 Prevoo M, Van'T Hof MA, Kuper H. et al. Modified disease activity scores that include twenty-eight-joint counts development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis & Rheumatology 1995; 38: 44-48
21 Aletaha D, Ward MM, Machold KP. et al. Remission and active disease in rheumatoid arthritis: Defining criteria for disease activity states. Arthritis & Rheumatology 2005; 52: 2625-2636
22 Van der Heijde D, Dankert T, Nieman F. et al. Reliability and sensitivity to change of a simplification of the Sharp/van der Heijde radiological assessment in rheumatoid arthritis. Rheumatology 1999; 38: 941-947
23 Brömme D, Lecaille F. Cathepsin K inhibitors for osteoporosis and potential off-target effects. Expert opinion on investigational drugs 2009; 18: 585-600
24 Smolen JS, Redlich K, Zwerina J. et al. Pro-inflammatory cytokines in rheumatoid arthritis. Clinical reviews in allergy & immunology 2005; 28: 239-248
25 Moon S-J, Hong Y-S, Ju JH. et al. Increased levels of interleukin 34 in serum and synovial fluid are associated with rheumatoid factor and anticyclic citrullinated peptide antibody titers in patients with rheumatoid arthritis. The Journal of rheumatology 2013; 40: 1842-1849
26 He W, Xu X-D, Dong Y-M. et al. Interleukin-34: A potential diagnostic and therapeutic target for rheumatoid arthritis. The Journal of rheumatology 2015; 42: 553-553
27 Zhang F, Ding R, Li P. et al. Interleukin-34 in rheumatoid arthritis: Potential role in clinical therapy. International journal of clinical and experimental medicine 2015; 8: 7809
28 Chang SH, Choi BY, Choi J. et al. Baseline serum interleukin-34 levels independently predict radiographic progression in patients with rheumatoid arthritis. Rheumatology international 2015; 35: 71-79
29 Kapoor M, Martel-Pelletier J, Lajeunesse D. et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011; 7: 33-42
30 Ciccia F, Alessandro R, Rodolico V. et al. IL-34 is overexpressed in the inflamed salivary glands of patients with Sjögren’s syndrome and is associated with the local expansion of pro-inflammatory CD14brightCD16+ monocytes. Rheumatology 2013; 52: 1009-1017
31 Li Z, Jin D, Wu Y. et al. Increased serum interleukin-34 in patients with coronary artery disease. Journal of International Medical Research 2012; 40: 1866-1870
32 Farrag DA, Asaad MK, Ghobrial CK. Evaluation of IL-34 in psoriasis and psoriatic arthritis patients: Correlation with disease activity and severity. The Egyptian Rheumatologist 2017; 39: 25-31