类风湿因子各亚型与 IgG 抗环瓜氨酸肽抗体的关系。

Relationship between rheumatoid factor isotypes and IgG anti-cyclic citrullinated peptide antibodies.

机构信息

Associated Regional and University Pathologists, Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, Utah 84108, USA.

出版信息

J Rheumatol. 2010 Aug 1;37(8):1582-8. doi: 10.3899/jrheum.091236. Epub 2010 Jun 1.

DOI:10.3899/jrheum.091236

PMID:20516016

Abstract

OBJECTIVE

To validate in a general patient population (GPP) the clinical value of measuring rheumatoid factor (RF) isotypes in relationship to IgG anti-cyclic citrullinated peptide (CCP) antibodies (CCP2 and CCP3).

METHODS

Serum samples were obtained as follows: 1021 GPP, for whom RF was ordered for diagnosis, 137 with rheumatoid arthritis (RA), 100 healthy blood donors (HBD), and 50 with systemic lupus erythematosus. Turbidimetry and ELISA were utilized for RF screening, and individual RF isotypes and IgG anti-CCP antibodies were measured by ELISA; RF IgG was measured after pepsin digestion.

RESULTS

We validated the generally accepted 90%-98% positive predictive value (PPV) and about 68% sensitivity of the anti-CCP2 test on our diagnosed cohorts as 96% (95% CI 89-99) and 65% (95% CI 56-73), respectively. The 282 RF IgM+ specimens identified in the GPP were subdivided into 3 subsets: (1) 83 as RF IgM+ IgG+ IgA+ with 63% (95% CI 51-73) anti-CCP2+ (i.e., sensitivity similar to the RA cohort); (2) 50 as RF IgM+ IgG- IgA+ with significantly fewer anti-CCP2+ (22%; 95% CI 12-36); and (3) about half as IgM+ IgG- IgA- with just 3% (95% CI 1-8) anti-CCP2+, i.e., not significantly different from the 1% (95% CI 0-5) in HBD. Thus, the chance for a specimen in the GPP to be anti-CCP2+ (i.e., to come from an RA patient) was increased by 7- and 21-fold, respectively, by identifying RF IgA and IgG in addition to IgM. About one-third of anti-CCP- RA patients in our cohort were RF IgM+ IgG+ IgA+, reflected as 3.4% in the anti-CCP2- GPP. The agreement between anti-CCP2 and anti-CCP3 was significantly higher for RF+ RA and GPP patients, 86% (95% CI 78-93) and 83% (95% CI 73-91), respectively, than for the RF- RA (27%; 95% CI 6-61), RF- GPP (4%; 95% CI 0-19), and non-RA controls. Anti-CCP2 but not anti-CCP3 significantly distinguished the HBD from the GPP (95% CI).

CONCLUSION

Measurement of the 3 isotypes of RF may increase by 7- to 21-fold the chance of making the serologic diagnosis of RA; a testing algorithm is proposed. The anti-CCP antibody response appears significantly less peptide-specific in the presence of IgM RF than in its absence.

摘要

目的

在一般患者人群（GPP）中验证测量类风湿因子（RF）同种型与 IgG 抗环瓜氨酸肽（CCP）抗体（CCP2 和 CCP3）之间的临床价值。

方法

采集以下血清样本：1021 例 GPP，这些患者因诊断需要而检测 RF；137 例类风湿关节炎（RA）患者；100 例健康献血者（HBD）；50 例系统性红斑狼疮患者。采用比浊法和 ELISA 法进行 RF 筛查，并用 ELISA 法测量各 RF 同种型和 IgG 抗 CCP 抗体；采用胃蛋白酶消化法测量 RF IgG。

结果

我们在确诊队列中验证了抗 CCP2 检测通常被接受的 90%-98%阳性预测值（PPV）和约 68%的灵敏度，其结果分别为 96%（95%CI 89-99）和 65%（95%CI 56-73）。在 GPP 中鉴定出的 282 份 RF IgM+标本分为 3 个亚组：（1）83 份为 RF IgM+ IgG+ IgA+，其中 63%（95%CI 51-73）为抗 CCP2+（即，与 RA 队列的敏感性相似）；（2）50 份为 RF IgM+ IgG- IgA+，抗 CCP2+的比例明显较低（22%；95%CI 12-36）；（3）约一半为 RF IgM+ IgG- IgA-，仅有 3%（95%CI 1-8）为抗 CCP2+，即与 HBD 中的 1%（95%CI 0-5）无显著差异。因此，与仅检测 IgM 相比，同时检测 IgA 和 IgG 可分别使 GPP 标本为抗 CCP2+（即来自 RA 患者）的机会增加 7 倍和 21 倍。在我们的队列中，约三分之一的抗 CCP-RA 患者为 RF IgM+ IgG+ IgA+，这在抗 CCP2- GPP 中反映为 3.4%。与 RF-RA（27%；95%CI 6-61）、RF-GPP（4%；95%CI 0-19）和非 RA 对照组相比，RF+RA 和 GPP 患者的抗 CCP2 与抗 CCP3 的一致性显著更高，分别为 86%（95%CI 78-93）和 83%（95%CI 73-91）。抗 CCP2 而非抗 CCP3 可显著区分 HBD 和 GPP（95%CI）。