Disssecting the roles of inflammatory mediators and cell death regulation in systemic lupus erythematosus: Paving the way for reliable diagnostic and prognostic tools

Impaired clearance of cellular debris is a key event in the pathogenesis of systemic lupus erythematosus (SLE), a condition characterised by multiple organ involvement, antinuclear autoantibodies (aAbs) and deposition of immune complexes (ICs) in target organs.

Autoantigens escaping physiological clearance can be excessively presented to the adaptive immune system, rendering loss of peripheral tolerance and a plethora of aAbs.

New insights of the pathogenesis are essential, and the discovery of biomarkers that accurately mirror disease activity, damage accrual and disease phenotypes is of utmost clinical importance. The pentraxin (PTX) C-reactive protein (CRP) seldom reflects disease activity in SLE.

We have described the mechanisms behind the uncoupling of correlation between IL-6 and CRP, and showed that aAbs to CRP occur in SLE, parallel disease activity and predict poor prognosis.

I have initiated a regional SLE cohort (Clinical Lupus Register in north-eastern Gothia, KLURING, now an important part of the Swedish SLE network) of incident and prevalent cases with biobank, PROMs and clinical follow-up data. KLURING (N>350) forms the basis of this translational project.

The specific aims of this project include: 1) Investigation of different aAbs and their diagnostic, prognostic and pathogenic implications; 2) Experimental studies on interactions between the type I interferon system, PTXs, ICs and complement proteins; 3) Biomarker evaluation to facilitate precision medicine