Atzeni Fabiola, Sarzi-Puttini Piercarlo, Dell' Acqua Donata, de Portu Simona, Cecchini Germana, Cruini Carola, Carrabba Mario, Meroni Pier Luigi
Rheumatology Unit, Department of Medicine, L Sacco University Hospital, 74 Via GB Grassi, 20157 Milano, Italy.
Arthritis Res Ther. 2006;8(1):R3. doi: 10.1186/ar1851.
Studies on autoantibody production in patients treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors reported contradictory results. We investigated in a prospective study the efficacy of a treatment with human monoclonal anti-TNF-alpha antibody (adalimumab) in patients with rheumatoid arthritis (RA) and we evaluated the relationship between treatment efficacy and the incidence and titers of disease-associated and non-organ-specific autoantibodies. Fifty-seven patients with RA not responsive to methotrexate and treated with adalimumab were enrolled. Antinuclear, anti-double-stranded(ds)DNA, anti-extractable nuclear antigens, anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI) autoantibodies, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies were investigated at baseline and after 6 and 12 months of follow-up. Comparable parameters were evaluated in a further 55 patients treated with methotrexate only. Treatment with adalimumab induced a significant decrease in RF and anti-CCP serum levels, and the decrease in antibody titers correlated with the clinical response to the therapy. A significant induction of antinuclear autoantibodies (ANA) and IgG/IgM anti-dsDNA autoantibodies were also found in 28% and 14.6% patients, respectively, whereas aCL and anti-beta2GPI autoantibodies were not detected in significant quantities. No association between ANA, anti-dsDNA, aCL and anti-beta2GPI autoantibodies and clinical manifestations was found. Clinical efficacy of adalimumab is associated with the decrease in RF and anti-CCP serum levels that was detected after 24 weeks and remained stable until the 48th week of treatment. Antinuclear and anti-dsDNA autoantibodies, but not anti-phospholipid autoantibodies, can be induced by adalimumab but to a lower extent than in studies with other anti-TNF blocking agents.
关于肿瘤坏死因子-α（TNF-α）抑制剂治疗患者自身抗体产生的研究报告了相互矛盾的结果。我们在一项前瞻性研究中调查了人源单克隆抗TNF-α抗体（阿达木单抗）治疗类风湿关节炎（RA）患者的疗效，并评估了治疗疗效与疾病相关及非器官特异性自身抗体的发生率和滴度之间的关系。纳入了57例对甲氨蝶呤无反应且接受阿达木单抗治疗的RA患者。在基线以及随访6个月和12个月后，检测了抗核抗体、抗双链（ds）DNA抗体、抗可提取核抗原抗体、抗心磷脂（aCL）抗体、抗β2糖蛋白I（抗β2GPI）抗体、类风湿因子（RF）和抗环瓜氨酸肽（抗CCP）抗体。另外55例仅接受甲氨蝶呤治疗的患者也评估了类似参数。阿达木单抗治疗使RF和抗CCP血清水平显著降低，抗体滴度的降低与治疗的临床反应相关。分别在28%和14.6%的患者中还发现了抗核自身抗体（ANA）和IgG/IgM抗dsDNA自身抗体的显著诱导，而未大量检测到aCL和抗β2GPI自身抗体。未发现ANA、抗dsDNA、aCL和抗β2GPI自身抗体与临床表现之间存在关联。阿达木单抗的临床疗效与24周后检测到并在治疗第48周前保持稳定的RF和抗CCP血清水平降低有关。阿达木单抗可诱导ANA和抗dsDNA自身抗体，但不能诱导抗磷脂自身抗体，且诱导程度低于其他抗TNF阻断剂的研究。
