Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis

被引:93
作者
Catrina, Anca I. [1 ]
Deane, Kevin D. [2 ]
Scher, Jose U. [3 ,4 ]
机构
[1] Karolinska Univ Hosp & Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden
[2] Univ Colorado, Sch Med, Div Rheumatol, Aurora, CO USA
[3] NYU, Sch Med, Dept Med, Div Rheumatol, New York, NY USA
[4] Hosp Joint Dis & Med Ctr, New York, NY USA
关键词
rheumatoid arthritis; environmental risk factors; genetic susceptibility; microbiome; break in tolerance; CITRULLINATED PEPTIDE ANTIBODIES; SECONDARY LYMPHOID ORGANS; HLA-DRB1 SHARED EPITOPE; INTESTINAL MICROBIOTA; GUT MICROBIOTA; CROHNS-DISEASE; T-CELLS; STAPHYLOCOCCUS-AUREUS; 1ST-DEGREE RELATIVES; PROTEIN ANTIBODIES;
D O I
10.1093/rheumatology/keu469
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
RA is a complex multifactorial chronic disease that transitions through several stages. Multiple studies now support that there is a prolonged phase in early RA development during which there is serum elevation of RA-related autoantibodies including RF and ACPAs in the absence of clinically evident synovitis. This suggests that RA pathogenesis might originate in an extra-articular location, which we hypothesize is a mucosal site. In discussing this hypothesis, we will present herein the current understanding of mucosal immunology, including a discussion about the generation of autoimmune responses at these surfaces. We will also examine how other factors such as genes, microbes and other environmental toxins (including tobacco smoke) could influence the triggering of autoimmunity at mucosal sites and eventually systemic organ disease. We will also propose a research agenda to improve our understanding of the role of mucosal inflammation in the development of RA.
引用
收藏
页码:391 / 402
页数:12
相关论文
共 124 条
  • [1] Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis
    Abdollahi-Roodsaz, Shahla
    Joosten, Leo A. B.
    Koenders, Marije I.
    Devesa, Isabel
    Roelofs, Mieke F.
    Radstake, Timothy R. D. J.
    Heuvelmans-Jacobs, Marleen
    Akira, Shizuo
    Nicklin, Martin J. H.
    Ribeiro-Dias, Fatima
    Van den Berg, Wim B.
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (01) : 205 - 216
  • [2] AHO K, 1995, J RHEUMATOL, V22, P2186
  • [3] Serum immunoglobulins and the risk of rheumatoid arthritis
    Aho, K
    Heliovaara, M
    Knekt, P
    Reunanen, A
    Aromaa, A
    Leino, A
    Kurki, P
    Heikkila, R
    Palosuo, T
    [J]. ANNALS OF THE RHEUMATIC DISEASES, 1997, 56 (06) : 351 - 356
  • [4] Aho K, 2000, J RHEUMATOL, V27, P2743
  • [5] AHO K, 1991, J RHEUMATOL, V18, P1282
  • [6] Community differentiation of the cutaneous microbiota in psoriasis
    Alekseyenko, Alexander V.
    Perez-Perez, Guillermo I.
    De Souza, Aieska
    Strober, Bruce
    Gao, Zhan
    Bihan, Monika
    Li, Kelvin
    Methe, Barbara A.
    Blaser, Martin J.
    [J]. MICROBIOME, 2013, 1
  • [7] STAPHYLOCOCCUS-AUREUS CARRIAGE IN TWINS
    ALY, R
    MAIBACH, HI
    SHINEFIELD, HR
    MANDEL, AD
    [J]. AMERICAN JOURNAL OF DISEASES OF CHILDREN, 1974, 127 (04): : 486 - 488
  • [8] Influence of Host Genetics and Environment on Nasal Carriage of Staphylococcus aureus in Danish Middle-Aged and Elderly Twins
    Andersen, Paal Skytt
    Pedersen, Jacob Krabbe
    Fode, Peder
    Skov, Robert L.
    Fowler, Vance G., Jr.
    Stegger, Marc
    Christensen, Kaare
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2012, 206 (08) : 1178 - 1184
  • [9] Tobacco Upregulates P. gingivalis Fimbrial Proteins Which Induce TLR2 Hyposensitivity
    Bagaitkar, Juhi
    Demuth, Donald R.
    Daep, Carlo Amorin
    Renaud, Diane E.
    Pierce, Deanne L.
    Scott, David A.
    [J]. PLOS ONE, 2010, 5 (05):
  • [10] Anti-Citrullinated Protein Antibodies in Unaffected First-Degree Relatives of Rheumatoid Arthritis Patients
    Barra, Lillian
    Scinocca, Mathias
    Saunders, Sheri
    Bhayana, Rajesh
    Rohekar, Sherry
    Racape, Maud
    Coles, Robert
    Cairns, Ewa
    Bell, David A.
    [J]. ARTHRITIS AND RHEUMATISM, 2013, 65 (06): : 1439 - 1447