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类风湿关节炎患者累积关节损伤模式的特征：临床、血清学及基因多态性视角

Characterization of cumulative joint damage patterns in patients with rheumatoid arthritis: a clinical, serological, and gene polymorphism perspective.

作者信息

Alarcon Renata Trigueirinho, Fernandes Artur da Rocha Corrêa, Laurindo Ieda Maria, Bértolo Manoel Barros, Pinheiro Geraldo Castelar, Andrade Luís Eduardo

机构信息

From the Rheumatology Division, Universidade Federal de São Paulo (UNIFESP), São Paulo; Rheumatology Division, Universidade Estadual do Rio de Janeiro (UERJ), Rio de Janeiro; Rheumatology Division, Universidade de São Paulo (USP); Rheumatology Division, Universidade Estadual de Campinas (UNICAMP), São Paulo, Brazil.Dr. Alarcon received an academic grant from CAPES (Brazilian Agency for Scientific Development) and Dr. Andrade receives a research grant from CNPq (Brazilian Agency for Research Development). Partially supported by grant # 07/50523-9 from the São Paulo Research Foundation.R.T. Alarcon, PhD, Research Fellow, Biol.; A.R.C. Fernandes, MD, PhD, Associate Professor, UNIFESP; I.M. Laurindo, MD, PhD, Associate Researcher, USP; M.B. Bértolo, MD, PhD, Associate Professor, UNICAMP; G.C. Pinheiro, MD, PhD, Associate Professor, UERJ; L.E. Andrade, MD, PhD, Associate Professor, UNIFESP.

出版信息

J Rheumatol. 2015 Mar;42(3):405-12. doi: 10.3899/jrheum.131177. Epub 2015 Feb 1.

DOI:10.3899/jrheum.131177

PMID:25641888

Abstract

OBJECTIVE

To characterize cumulative joint damage (CJD) patterns in rheumatoid arthritis (RA) and determine their associations with demographic/clinical features and HLA-DRB1 gene polymorphism.

METHODS

Hand and foot radiographs were obtained from 404 patients with RA. CJD patterns were determined by 3 derivations from Sharp/van der Heijde scores, obtained by the mathematical division of scores for hands/feet (Sharp-h/f score), fingers/wrists (Sharp-f/w score), and erosion/space narrowing (Sharp-e/sn score), respectively. DNA and serum were obtained for determination of HLA-DRB1 polymorphism, rheumatoid factor (RF), and anticitrullinated protein antibodies (ACPA).

RESULTS

Patients with wrist-dominant CJD pattern were more likely to have severe RA than those with finger-dominant pattern (68.4% vs 46.0%; p = 0.036) as were those with foot-dominant vs hand-dominant CJD pattern (76.5% vs 56.4%; p = 0.044). HLA-DRB1 shared epitope (SE) alleles were associated with erosion-dominant CJD pattern (p = 0.021). Patients with erosion-dominant CJD pattern had higher levels of RF and ACPA than those with space-narrowing-dominant CJD pattern (median RF 71.35 U/ml vs 22.05 U/ml, respectively; p = 0.003; median ACPA 187.9 U/ml vs 143.2 U/ml, respectively; p < 0.001). The majority of triple-positive patients (SE+, RF+, ACPA+) had erosion-dominant CJD pattern (62.3%) while the majority of triple-negative patients (SE-, FR-, ACPA-) had space narrowing-dominant CJD pattern (75%; p = 0.017). ACPA was associated with HLA-DRB1 SE alleles (p < 0.05). Patients with foot-dominant CJD pattern were taller than those with hand-dominant CJD pattern (p = 0.002); those with erosion-dominant CJD pattern had higher weight and body mass index than those with space narrowing-dominant CJD pattern (p = 0.014, p = 0.001).

CONCLUSION

CJD patterns were associated with disease severity, HLA-DRB1 SE status, presence and titer of ACPA and RF, and morphometric features.

摘要

目的

描述类风湿关节炎（RA）中累积关节损伤（CJD）模式，并确定其与人口统计学/临床特征及HLA - DRB1基因多态性的关联。

方法

获取了404例RA患者的手和足部X线片。CJD模式通过Sharp/van der Heijde评分的3种衍生方式确定，分别通过手部/足部评分（Sharp - h/f评分）、手指/腕部评分（Sharp - f/w评分）以及侵蚀/关节间隙变窄评分（Sharp - e/sn评分）的数学划分得出。采集DNA和血清用于测定HLA - DRB1多态性、类风湿因子（RF）和抗瓜氨酸化蛋白抗体（ACPA）。

结果

与以手指为主的CJD模式患者相比，以腕部为主的CJD模式患者更易患有重度RA（68.4%对46.0%；p = 0.036），以足部为主的CJD模式患者与以手部为主的CJD模式患者相比情况类似（76.5%对56.4%；p = 0.044）。HLA - DRB1共享表位（SE）等位基因与以侵蚀为主的CJD模式相关（p = 0.021）。与以关节间隙变窄为主的CJD模式患者相比，以侵蚀为主的CJD模式患者的RF和ACPA水平更高（RF中位数分别为71.35 U/ml对22.05 U/ml；p = 0.003；ACPA中位数分别为187.9 U/ml对143.2 U/ml；p < 0.001）。大多数三阳性患者（SE +、RF +、ACPA +）具有以侵蚀为主的CJD模式（62.3%），而大多数三阴性患者（SE -、FR -、ACPA -）具有以关节间隙变窄为主的CJD模式（75%；p = 0.017）。ACPA与HLA - DRB1 SE等位基因相关（p < 0.05）。以足部为主的CJD模式患者比以手部为主的CJD模式患者更高（p = 0.002）；以侵蚀为主的CJD模式患者比以关节间隙变窄为主的CJD模式患者体重和体重指数更高（p = 0.014，p = 0.001）。