REPORT

Genetics

What precedes development of rheumatoid arthritis?

L Klareskog¹, L Alfredsson², S Rantapää-Dahlqvist³, E Berglin³, P Stolt², L Padyukov¹

¹ Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden
² Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
³ Department of Rheumatology, Umeå University and University Hospital, Umeå, Sweden

Correspondence to:
Correspondence to:
L Klareskog
Rheumatology Unit, Department of Medicine, Karolinska University Hospital, 171 76 Stockholm, Sweden; Lars.Klareskog{at}medks.ki.se

Studies on aetiology of inflammatory diseases such as rheumatoid arthritis (RA) need to investigate the potential environmental triggers that are active before onset of disease, the genetic context in which these triggers act, and whether the presence of such triggers in an arthritis prone genetic context will give rise to the immune reactions associated with/preceding RA. Such knowledge would help not only to address much better the issue of causality of these potential triggers and the immune reactions, but also to carry out various interventions aimed at influencing the disease provoking immune events before development of clinical signs of disease.

This short report summarises recent data demonstrating (a) the presence of anticitrullin antibodies or rheumatoid factors in between a third and half of patients with RA before development of clinical signs; (b) long term smoking is associated with a high risk of future development of seropositive but not seronegative RA; and (c) a strong gene–environment interaction between smoking and SE genes in the development of seropositive RA.

We conclude that, in a certain genetic context, smoking is a potential trigger of RA, and a combination of the two factors is associated with the occurrence of immune reactions long before the onset of RA.

Abbreviations: RA, rheumatoid arthritis, RF, rheumatoid factor; SE, shared epitope

Keywords: rheumatoid arthritis; anticitrullin antibodies; trigger; rheumatoid factor; smoking; SE genes

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• GANDJBAKHCH, F., FAJARDY, I., FERRE, B., DUBUCQUOI, S., FLIPO, R.-M., ROGER, N., SOLAU-GERVAIS, E. (2009). A Functional Haplotype of PADI4 Gene in Rheumatoid Arthritis: Positive Correlation in a French Population. The Journal of Rheumatology 36: 881-886 [Abstract] [Full Text]  
• Jorgensen, K T, Wiik, A, Pedersen, M, Hedegaard, C J, Vestergaard, B F, Gislefoss, R E, Kvien, T K, Wohlfahrt, J, Bendtzen, K, Frisch, M (2008). Cytokines, autoantibodies and viral antibodies in premorbid and postdiagnostic sera from patients with rheumatoid arthritis: case-control study nested in a cohort of Norwegian blood donors. Ann Rheum Dis 67: 860-866 [Abstract] [Full Text]  
• Majka, D S, Deane, K D, Parrish, L A, Lazar, A A, Baron, A E, Walker, C W, Rubertone, M V, Gilliland, W R, Norris, J M, Holers, V M (2008). Duration of preclinical rheumatoid arthritis-related autoantibody positivity increases in subjects with older age at time of disease diagnosis. Ann Rheum Dis 67: 801-807 [Abstract] [Full Text]