Innala Lena, Kokkonen Heidi, Eriksson Catharina, Jidell Erik, Berglin Ewa, Dahlqvst Solbritt Rantapää
Department of Rheumatology, Department of Clinical Immunology, and Department of Transfusion Medicine, University Hospital, Umeå, Sweden.
J Rheumatol. 2008 Jun;35(6):1002-8. Epub 2008 Apr 1.
To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA).
The ACPA, e.g., antibodies against mutated citrullinated vimentin (MCV), cyclic citrullinated peptides (CCP) type 2 and 3 (both of IgG isotype) and 3.1 (of both IgG and IgA isotypes), were analyzed at baseline in patients with early RA (n = 210) and in population controls (n = 102) using an enzyme immunoassay. A receiver-operating characteristic curve was constructed for each antibody. Disease activity [swollen and tender joints, visual analog scale for global health, and erythrocyte sedimentation rate (ESR)] was evaluated at baseline and regularly for 24 months. Radiographs of hands and feet were graded using the Larsen score.
Patients with anti-MCV antibodies had significantly less reduction in Disease Activity Score (DAS28) over time (p < 0.01), and significantly increased area under the curve (AUC) for DAS28 (p < 0.05), ESR (p < 0.01), C-reactive protein (p < 0.01), and swollen joint count (p = 0.057) compared to those without. Corresponding differences were not found in patients with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression (p < 0.0001-0.01) and radiological outcome (p < 0.0001-0.01) at 24 months were significantly predicted by all ACPA after baseline adjustments. PTPN22 T variant and HLA-DRB1 alleles were not related to radiological progression or inflammatory activity over time.
Anti-MCV antibodies are associated with a more severe RA disease, as measured by DAS28, ESR, and swollen joint count over time, compared with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression was predicted equally by all 4 autoantibodies.
评估各种抗瓜氨酸化肽蛋白（ACPA）抗体对早期类风湿关节炎（RA）疾病进展的预测价值及其与蛋白酪氨酸磷酸酶非受体型22（PTPN22）1858C/T多态性和人类白细胞抗原DRB1（HLA - DRB1）等位基因的关系。
采用酶免疫分析法，在早期RA患者（n = 210）和人群对照（n = 102）的基线水平分析ACPA，例如抗突变型瓜氨酸波形蛋白（MCV）抗体、2型和3型环状瓜氨酸肽（CCP，均为IgG同种型）以及3.1型（IgG和IgA同种型均有）抗体。为每种抗体构建受试者工作特征曲线。在基线水平以及定期随访24个月时评估疾病活动度[肿胀和压痛关节数、整体健康视觉模拟评分以及红细胞沉降率（ESR）]。使用 Larsen 评分对手和足的X线片进行分级。
与未检测到抗MCV抗体的患者相比，检测到抗MCV抗体的患者随时间推移疾病活动评分（DAS28）降低幅度显著更小（p < 0.01），且DAS28、ESR（p < 0.01）、C反应蛋白（p < 0.01）和肿胀关节计数（p = 0.057）的曲线下面积（AUC）显著增加。在检测到抗CCP2、CCP3和CCP3.1抗体的患者中未发现相应差异。在基线调整后，所有ACPA均能显著预测24个月时的放射学进展（p < 0.0001 - 0.01）和放射学结局（p < 0.0001 - 0.01）。PTPN22 T变异体和HLA - DRB1等位基因与随时间的放射学进展或炎症活动无关。
与抗CCP2、CCP3和CCP第3.1抗体相比，通过随时间的DAS28、ESR和肿胀关节计数衡量，抗MCV抗体与更严重的RA疾病相关。所有4种自身抗体对放射学进展的预测能力相同。
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