用于诊断抗环瓜氨酸肽(CCP)抗体阴性患者类风湿关节炎及监测英夫利昔单抗治疗的抗突变瓜氨酸波形蛋白抗体

Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy.

作者信息

Nicaise Roland Pascale, Grootenboer Mignot Sabine, Bruns Alessandra, Hurtado Margarita, Palazzo Elisabeth, Hayem Gilles, Dieudé Philippe, Meyer Olivier, Chollet Martin Sylvie

机构信息

Immunology and Haematology Department, Bichat-Claude Bernard Teaching Hospital, AP-HP, Paris Cedex 18, France.

出版信息

Arthritis Res Ther. 2008;10(6):R142. doi: 10.1186/ar2570. Epub 2008 Dec 10.

Abstract

INTRODUCTION

Antibodies against cyclic citrullinated peptides (CCPs) are useful for diagnosing rheumatoid arthritis (RA). Antibodies to mutated citrullinated vimentin (MCV) were described recently in RA. The aims of this study were to evaluate the usefulness of anti-MCV for diagnosing RA in anti-CCP-negative patients and to monitor anti-MCV titres during infliximab therapy for RA.

METHODS

We studied two groups of RA patients, one with (n = 80) and one without (n = 76) anti-CCP antibodies. The specificity of anti-MCV was evaluated by investigating 50 healthy controls and 158 patients with other rheumatic diseases (51 psoriatic rheumatism, 58 primary Sjögren syndrome, and 49 ankylosis spondylitis). Serum anti-MCV and anti-CCP titres were measured in 23 patients after 6, 12, 18, and 24 months of infliximab treatment. Anti-CCP2 and anti-MCV levels were assayed using a commercial enzyme-linked immunosorbent assay. IgM rheumatoid factor was determined by nephelometry.

RESULTS

In accordance with the cutoff values recommended by the manufacturer, the specificity of anti-MCV antibodies was 90.9%. We adjusted the cutoff values to obtain the same specificity as that of anti-CCP antibodies (94.2%). With this optimal cutoff, anti-MCV antibodies were found in 11.8% (9/76) of RA patients without anti-CCP, and similarly, anti-CCP antibodies were found in 11.2% (9/80) of RA patients without anti-MCV. Anti-MCV antibodies were positive in 6 patients who tested negative for both anti-CCP and rheumatoid factor. Anti-MCV titres were significantly decreased after 18 and 24 months of infliximab therapy compared with baseline (P < 0.01) as a significant decrease of anti-CCP levels occurred only at 24 months (P < 0.04). Moreover, an anti-MCV decrease was significantly associated with DAS28 (disease activity score using 28 joint counts) improvements 12 months into therapy.

CONCLUSIONS

Our results suggest that anti-MCV antibodies may be valuable for diagnosing RA in anti-CCP-negative patients without replacing them as an equivalent number of anti-CCP-positive RA patients test negative for anti-MCV. Moreover, anti-MCV antibodies could be useful for monitoring the effects of infliximab therapy.

摘要

引言

抗环瓜氨酸肽(CCP)抗体对类风湿关节炎(RA)的诊断很有用。最近在类风湿关节炎中发现了抗突变型瓜氨酸波形蛋白(MCV)抗体。本研究的目的是评估抗MCV抗体在抗CCP阴性患者中对类风湿关节炎诊断的有用性,并监测类风湿关节炎患者英夫利昔单抗治疗期间抗MCV抗体滴度。

方法

我们研究了两组类风湿关节炎患者,一组有抗CCP抗体(n = 80),另一组无抗CCP抗体(n = 76)。通过调查50名健康对照者和158名其他风湿性疾病患者(51例银屑病关节炎、58例原发性干燥综合征和49例强直性脊柱炎)来评估抗MCV抗体的特异性。在23例患者接受英夫利昔单抗治疗6、12、18和24个月后,检测血清抗MCV和抗CCP抗体滴度。使用商业酶联免疫吸附测定法检测抗CCP2和抗MCV水平。通过散射比浊法测定IgM类风湿因子。

结果

根据制造商推荐的临界值,抗MCV抗体的特异性为90.9%。我们调整临界值以获得与抗CCP抗体相同的特异性(94.2%)。采用这个最佳临界值,在无抗CCP抗体的类风湿关节炎患者中,11.8%(9/76)检测到抗MCV抗体;同样,在无抗MCV抗体的类风湿关节炎患者中,11.2%(9/80)检测到抗CCP抗体。在抗CCP和类风湿因子检测均为阴性的6例患者中,抗MCV抗体呈阳性。与基线相比,英夫利昔单抗治疗18和24个月后抗MCV抗体滴度显著降低(P < 0.01),而抗CCP水平仅在24个月时显著降低(P < 0.04)。此外,治疗12个月时抗MCV抗体降低与疾病活动评分(使用28个关节计数的疾病活动评分)改善显著相关。

结论

我们的结果表明,抗MCV抗体对诊断抗CCP阴性的类风湿关节炎患者可能有价值,但不能替代抗CCP抗体,因为相当数量的抗CCP阳性类风湿关节炎患者抗MCV检测为阴性。此外,抗MCV抗体可能有助于监测英夫利昔单抗治疗的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f0c/2656247/6ab01baa5298/ar2570-1.jpg

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