Defining Biological Subsets in Systemic Lupus Erythematosus: Progress Toward Personalized Therapy

Abstract

Systemic lupus erythematosus (SLE) is a heterogeneous disease with respect to disease severity, response to treatment, and organ damage, the pathogenesis of which includes immunological mechanisms that are driven by both genetic and environmental factors. There are clear differences in the pathogenesis of SLE between patients of different ancestral backgrounds, including differences in genetic risk factors, immunological parameters, and clinical manifestations. Patients with high and low levels of type I interferon (IFN) in circulation represent one major biological subset within SLE, and these two groups of patients are present in all ancestral backgrounds. Genetic factors, autoantibodies, and levels of other cytokines all differ between high and low IFN patients. This distinction has also been important in predicting response to treatment with anti-type I IFN therapies, providing a precedent in SLE for biological subsets predicting treatment response. This review highlights some recent developments in defining biological subsets of SLE based on disease pathophysiology, and we speculate how this improved knowledge of disease heterogeneity will inform our efforts to personalize therapy in this disease.

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Correspondence to Timothy B. Niewold.

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Dr Sinicato, Dr Postal, and Dr Appenzeller have no conflicts to declare. Dr Niewold received research grants from EMD Serono and Janssen, Inc. These companies had no role in the preparation of this manuscript.

Grants

S. Appenzeller: Fundação Apoio À Pesquisa Estado São Paulo-Brasil (FAPESP 2008/02917-0, 2009/06049-6, and 2009/15286-1), Conselho Nacional Pesquisa Desenvolvimento-Brasil CNPq (300447/2009-4, 471343/2011-0, 302205/2012-8, and 473328/2013-5).

T.B. Niewold: National Institutes of Health (NIH) Grants (AR060861, AR057781, AR065964, and AI071651), Alliance for Lupus Research, Rheumatology Research Foundation, Cure JM Foundation, The Myositis Foundation, the Mayo Clinic Foundation, the Lupus Research Institute, and the Lupus Foundation of Minnesota.

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Sinicato, N.A., Postal, M., Appenzeller, S. et al. Defining Biological Subsets in Systemic Lupus Erythematosus: Progress Toward Personalized Therapy. Pharm Med 31, 81–88 (2017). https://doi.org/10.1007/s40290-017-0178-6

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Keywords

  • Systemic Lupus Erythematosus
  • Systemic Lupus Erythematosus Patient
  • Lupus Nephritis
  • African American
  • Belimumab