Prevention of autoimmune rheumatic disease: state of the art and future perspectives

Prevention of disease can in principle be accomplished by identification of environmental and/or lifestyle risk and protective factors followed by public health measures (such as for smoking and lung cancer), or by modification of the individual's reactions to disease-inducing factors (such as in vaccinations against microbes). This review discusses both options based on emerging understanding of aetiologies in inflammatory rheumatic diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The major current opportunity for public health-based prevention lies in avoiding smoking. In RA, recent studies have calculated that, in Sweden (a country characterised by a low frequency of smoking), 20% of all RA cases and 33% of all cases of ACPA-positive RA would not have occurred in a smoke-free society. Smoking is also a major risk factor for SLE but no population attribution is yet available. New avenues for individualised and biology-based prevention are provided by the demonstration that several autoimmune rheumatic diseases are preceded by emergence of subclinical autoimmunity followed by laboratory-based signs of inflammation and finally overt disease. Examples of this process are provided from studies of autoimmunity to citrullinated proteins (in RA), to dsDNA (in SLE in general) and to Ro52 epitopes (in the case of neonatal heart block). The recognition of this sequence of events provides opportunities to intervene specifically and potentially curatively before onset of full-blown disease. Such prevention can be accomplished by modification of inciting antigens (environment), by modification of immunity (more or less specific immunomodulation) or by modification of specific gene functions. In all cases, prevention will be different in different subsets of disease and differ at different time points of disease development. Thus, the road map towards prevention of autoimmune rheumatic diseases includes increased understanding of how genes, environment and immunity interact.