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

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

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