Insulin-like growth factor-1 (IGF1) in systemic lupus erythematosus: relation to disease activity,organ damage and immunological findings

Abstract

Background

Insulin growth factor-1 (IGF1) activates cell proliferation pathways and inhibits apoptosis. IGF1 is involved in tumour growth and required for T-cell independent activation of B cells. Activated B cells and autoantibody production are a hallmark of systemic lupus erythematosus (SLE). To investigate the possible role of IGF1 in SLE, we studied IGF1 across clinical characteristics, immunological biomarkers, disease activity and organ damage in SLE patients.

Method

In a cross-sectional study, we collected clinical characteristics, medication, disease activity (SLEDAI-2K) and organ damage (SDI) for 94 SLE patients. Autoantibodies and cytokines were measured by ELISA, and levels of IGF1 and IGF binding protein 3 (IGFBP3) by chemiluminescence. Free IGF1 was estimated by the IGF1:IGFBP3 ratio. Healthy controls served as a comparator group.

Results

There was a significant age-related decline in IGF1, IGFBP3 and free IGF1 (IGF1:IGFBP3 ratio) that was similar in SLE patients and controls with very few outliers. Free IGF1 was inversely related to blood pressure (Rs −0.327, p < 0.01) and HbA1c (Rs −0.31, p < 0.01). Free IGF1 was higher in disease-modifying antirheumatic drug-treated patients (p < 0.01), but there was no significant association between the IGF1 axis and autoantibody profiles, cytokine levels or SLEDAI-2K or SDI categories. IGF1 correlated inversely with BAFF level and B, natural killer and CD8 + cell counts.

Conclusion

Free IGF1 levels in SLE patients declined appropriately with age. IGF1 levels were not associated with disease activity, severity or autoantibody levels in SLE. Free IGF1 had positive metabolic effects in SLE and may play an indirect role in dampening the cellular immune response by downregulating B- and T-cell activity.

Keywords

Cardiovascular disease musculoskeletal systemic lupus erythematosus

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