Tài liệu Báo cáo khoa học: Molecular aspects of rheumatoid arthritis: role of environmental factors

MINIREVIEW

Molecular aspects of rheumatoid arthritis: role of

environmental factors

Shu Kobayashi, Shigeki Momohara, Naoyuki Kamatani and Hiroshi Okamoto

Institute of Rheumatology, Tokyo Women’s Medical University, Japan

Introduction

Rheumatoid arthritis (RA) is a systemic, chronic

inflammatory disease that affects 0.5–1% of the popu￾lation and causes progressive joint destruction that

leads to the restriction of activities of daily living and

deterioration of quality of life. Although the patho￾genesis of RA has not yet been fully elucidated, it is

considered to be a complex, multifarious disease that

is influenced by both genetic and environmental fac￾tors. Genetic influences that contribute to RA suscepti￾bility have been demonstrated in both studies of twins

[1] and families [2], as well as in genome-wide linkage

scans [3]. These studies estimated that genetic factors

are responsible for 50–60% of the risk of developing

RA and that environmental factors may explain the

remaining risk. This quantification was made by a

classical approach to separating the quantitative

influence of genetic factors in RA with nationwide

studies of twins with RA, as described previously [1].

This minireview focuses on the contribution of envi￾ronmental risk factors to the development of RA.

Infection

Several infectious agents have been reported to be risk

factors for RA (Table 1), including human parvovirus

B19 (B19), Epstein–Barr virus (EBV), retroviruses,

alphaviruses, hepatitis B virus, Mycobacterium tuberculo￾sis, Escherichia coli, Proteus mirabilis and Mycoplasma.

Human parvovirus B19 is a small, nonenveloped

DNA virus that is transmitted via the respiratory tract

as well as vertically from mother to fetus. Although

B19 is a significant human pathogen with a wide

Keywords

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD);

cytokines; environmental factors; hormone;

NF-jB; rheumatoid arthritis; smoking;

weather

Correspondence

H. Okamoto, Institute of Rheumatology,

Tokyo Women’s Medical University, 10-22

Kawada-cho, Shinjuku, Tokyo 162-0054,

Japan

Fax: +81 3 5269 1726

Tel: +81 3 5269 1725

E-mail: [email protected]

(Received 14 March 2008, revised 1 June

2008, accepted 20 June 2008)

doi:10.1111/j.1742-4658.2008.06581.x

Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease that

affects 0.5–1% of the population. RA causes progressive joint destruction

that leads to the restriction of activities of daily living and deterioration of

quality of life. Although the pathogenesis of RA has not yet been fully elu￾cidated, it is considered to be a complex, multifarious disease that is influ￾enced by both genetic and environmental factors. Genetic influences that

contribute to RA susceptibility have been demonstrated both in studies of

twins and families, as well as in genome-wide linkage scans, and it is esti￾mated that genetic factors are responsible for 50–60% of the risk of devel￾oping RA. Thus, environmental factors may explain the remaining risk of

developing RA. A large variety of environmental factors such as infectious

agents, smoking, sex hormones, pregnancy etc. have been extensively

studied previously. Understanding of how these factors contribute to the

development of RA may lead to the better understanding of pathogenesis

of RA.

Abbreviations

AhR, aryl hydrocarbone receptor; B19, human parvovirus B19; CCP, cyclic citrullinated peptide; EBV, Epstein–Barr virus; HLA, human

leukocyte antigen; IL, interleukin; JCP, Japanese cedar pollinosis; RA, rheumatoid arthritis; RF, rheumatoid factor; TCDD, 2,3,7,8-

tetrachlorodibenzo-p-dioxin; Th, T helper; TNF-a, tumor necrosis factor-a.

4456 FEBS Journal 275 (2008) 4456–4462 ª 2008 The Authors Journal compilation ª 2008 FEBS