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.

Interleukin 34 (IL-34) is a recently discovered cytokine that binds macrophage colony-stimulating factor (M-CSF) receptor. Rheumatoidarthritis (RA) is characterized by increased osteoclastogenesis. To identify the significance of IL-34 in RA, the IL-34 concentration was measured in serum and synovial fluid (SF).

METHODS:

IL-34 concentrations were measured in serum from patients with RA (n = 113), patients with osteoarthritis (OA; n = 56), and controls (n = 36), and in SF isolated from patients with RA (n = 36) or OA (n = 24). Correlations between serum IL-34 levels and clinical features in RA were assessed. The levels of IL-1β, IL-6, IL-17α, interferon-γ-induced protein 10, receptor activator of nuclear factor κB ligand (RANKL), and Dickkopf-1 were also measured.

RESULTS:

Patients with RA had a higher mean serum level of IL-34 than did patients with OA and controls (188.0 ± 550.3, 36.6 ± 38.0, and 49.1 ± 78.5 pg/ml, respectively). Similarly, SF IL-34 concentration was higher in patients with RA than in those with OA. IL-34 levels were positively associated with IL-6 levels in serum from patients with RA and OA. SF IL-34 concentration correlated significantly with IL-6 and RANKL levels only in RA. The serum level of IL-34 was not correlated with systemic osteoporosis and radiographic joint damage in RA. IL-34 levels in the serum from patients with RA were positively correlated with rheumatoid factor and anticyclic citrullinated peptide antibody titers (r = 0.282 and 0.491, respectively).

CONCLUSION:

Circulating IL-34 levels in RA correlated with autoantibody production. Further investigations of localized and systemic effects of IL-34 are warranted to elucidate RA pathogenesis.

最近一期J Rheumatol杂志发表了上述文章，作者通过比较类风湿性关节炎患者，骨关节炎患者和健康人群血清和关节液中的IL-34水平，发现该因子在类风湿性关节炎患者血清和关节液中高表达，并与患者IL-6水平，RANKL水平，类风湿因子和ACAP抗体滴度相关，表明IL-34在类风湿性关节炎发生发展中可能发挥一定的病理作用。

类风湿性关节炎是一种以关节侵蚀为特点的自身免疫性疾病。其病变特点主要为滑膜炎，然后导致关节软骨破坏，从而影响患者的关节功能和生活质量。目前，对类风湿性关节炎的发病机制尚不完全了解，很多研究表明，其发生可能与白介素相关，如白介素1，白介素17等。白介素是一种细胞因子，最早发现在白细胞中表达，作为细胞间信号传递的手段。人体免疫系统功能的正常发挥，在很大程度上依赖于白介素的功能，当白介素功能异常时，可导致自身免疫性疾病。

白介素34是白介素家族中的一个细胞因子，主要在人体脾脏中表达，也在胸腺，肝脏，小肠，结肠等位置表达，可在单核细胞中发挥作用。有意思的是，IL-34可以结合到M-CSF受体上。因此M-CSF/M-CSF受体系统是人体破骨细胞分化的关键通路之一，所以，IL-34在类风湿性关节炎中表达的异常，以及其与M-CSF受体结合，可能关系到类风湿性关节炎患者体内的破骨细胞形成，从而影响关节软骨下骨，进而影响关节功能。但IL-34在类风湿性关节炎患者中的病理机制，仍有待进一步研究。