PRediction Of Flares In Lupus With autoantibodiEs and Chemokines

Systemic lupus erythematosus (SLE) is a chronic relapsing-remitting autoimmune disease with a wide range of clinical manifestations affecting several organs. Although the management of lupus patients has improved in the last years, accurate models for predicting disease progression are lacking.

In clinical practice, SLE patients can be categorized into three groups:

1. A large group of patients has 'quiescent' disease; after diagnosis of SLE and possibly a short induction treatment with corticosteroids, patients remain in a state of remission for years with hydroxychloroquine treatment only.
2. A substantial group of patients has relapsing-and-remitting disease, with mostly cutaneous inflammation but without further organ involvement.
3. A smaller group of patients has severe inflammation with extensive organ involvement, including lupus nephritis and neuropsychiatric SLE (npSLE) as the most threatening complications.

This stratification of patients is reflected by the frequency of hospital visits. Patients with more severe disease activity have a higher frequency of visits to the outpatient clinic and more frequently receive biologicals.(1) In the UMC Utrecht, patients in group 1. normally visit the outpatient clinic on a yearly basis, patients in group 2. visit 2-4 times a year and patients in group 3. are seen more frequently. However, some patients with quiescent disease for years can still present with an SLE exacerbation, and patients with frequent bouts of inflammation can eventually reach a remission state.

It would be of great value to be able to distinguish these patient categories early after diagnosis. This would aid the clinician in identifying those patients who can safely visit the outpatient clinic only once a year, and conversely, it would be possible to point out which patients should be monitored more closely. Ideally, this early distinction would also correspond with treatment decisions, that is, intensifying treatment when a flare is suspected, or tapering medication when there is a low risk profile. The ultimate goal would be to enable clinicians to identify high risk patients and to treat them with immunomodulating therapy before any inflammatory damage has occurred, for instance with the combination of rituximab and belimumab as is being studied right now.(2,3) The pathogenesis of SLE is highly complex. Genetic predispositions, proinflammatory and anti-inflammatory cytokines, autoantibodies, lymphocyte subset abnormalities as well as defects in the complement systems all have putative roles in the development of SLE. At present, tools that enable early patient stratification are lacking. Furthermore - except for a possible association of rise in anti-dsDNA-antibodies and the development of lupus nephritis - factors that can predict SLE flares have not been identified.