Division of Pharmacology and Pathophysiology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.
Ann Rheum Dis. 2010 Dec;69(12):2137-44. doi: 10.1136/ard.2009.126441. Epub 2010 Aug 2.
Immunoglobulin (Ig) free light chains (FLCs) are short-lived B cell products that contribute to inflammation in several experimental disease models. In this study, FLC concentrations in inflamed joints of patients with rheumatoid arthritis (RA) as compared to patients with osteoarthritis were investigated. In addition, the relationship of FLCs and disease activity upon B cell depletion (rituximab) in patients with RA was studied.
Synovial fluid (SF) and tissue from patients with RA were analysed for local presence of FLCs using ELISA and immunohistochemistry. In addition, FLC concentrations were measured (at baseline, 3 and 6 months after treatment) in 50 patients with RA with active disease who were treated with rituximab. Changes in FLCs were correlated to changes in disease activity and compared to alterations in IgM, IgG, IgA, IgM-rheumatoid factor (RF) and IgG-anti-citrullinated protein antibody (ACPA) concentrations.
FLCs were detected in synovial tissue from patients with RA, and high FLC concentrations were found in SF from inflamed joints, which positively correlate with serum FLC concentrations. Serum FLC concentrations significantly correlated with disease activity score using 28 joint counts, erythrocyte sedimentation rate (ESR) and C reactive protein, and changes in FLC correlated with clinical improvement after rituximab treatment. Moreover, effect of treatment on FLC concentrations discriminated clinical responders from non-responders, whereas IgM-RF and IgG-ACPA significantly decreased in both patient groups.
FLCs are abundantly present in inflamed joints and FLC levels correlate with disease activity. The correlation of FLC concentrations and disease activity indicates that FLCs may be relevant biomarkers for treatment response to rituximab in patients with RA and suggests that targeting FLC may be of importance in the therapy of RA.
免疫球蛋白（Ig）游离轻链（FLC）是短寿命的 B 细胞产物，在几种实验性疾病模型中可引起炎症。在这项研究中，比较了类风湿关节炎（RA）患者与骨关节炎患者的炎症关节中 FLC 浓度。此外，还研究了 RA 患者 B 细胞耗竭（利妥昔单抗）后 FLC 与疾病活动度的关系。
采用 ELISA 和免疫组化法分析 RA 患者的滑膜液（SF）和组织中 FLC 的局部存在。此外，还对 50 例活动期 RA 患者进行了治疗，在基线、治疗后 3 个月和 6 个月时测量了 FLC 浓度，这些患者接受了利妥昔单抗治疗。FLC 的变化与疾病活动度的变化相关，并与 IgM、IgG、IgA、IgM-类风湿因子（RF）和 IgG-抗瓜氨酸蛋白抗体（ACPA）浓度的变化进行了比较。
在 RA 患者的滑膜组织中检测到 FLC，在炎症关节的 SF 中发现了高浓度的 FLC，其与血清 FLC 浓度呈正相关。血清 FLC 浓度与 28 个关节计数、红细胞沉降率（ESR）和 C 反应蛋白的疾病活动评分显著相关，并且在利妥昔单抗治疗后临床改善时 FLC 的变化也与之相关。此外，治疗对 FLC 浓度的影响可将临床应答者与非应答者区分开来，而在两组患者中，IgM-RF 和 IgG-ACPA 均显著降低。
FLC 在炎症关节中大量存在，并且 FLC 水平与疾病活动度相关。FLC 浓度与疾病活动度的相关性表明，FLC 可能是 RA 患者对利妥昔单抗治疗反应的相关生物标志物，并提示靶向 FLC 可能对 RA 的治疗具有重要意义。
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