Of interest, patients with this subgroup of disease typically describe a shorter symptom duration when they present with arthritis, but with evidence for more prominent IL-6-mediated lymphocyte activation in the periphery, compared with their seropositive counterparts [24,25], consistent with a more ‘explosive’, pro-inflammatory component to the natural history of seronegative disease (Fig. 1). The gene discussed is IL6; the disease is arthritic joint disease.