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Membrane-Bound Complement Regulatory Proteins as Biomarkers and Potential Therapeutic Targets for SLE

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Complement Therapeutics

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 735))

Abstract

For the last two decades, there had been remarkable advancement in understanding the role of complement regulatory proteins in autoimmune disorders and importance of complement inhibitors as therapeutics. Systemic lupus erythematosus is a prototype of systemic autoimmune disorders. The disease, though rare, is potentially fatal and afflicts women at their reproductive age. It is a complex disease with multiorgan involvement, and each patient presents with a different set of symptoms. The diagnosis is often difficult and is based on the diagnostic criteria set by the American Rheumatology Association. Presence of antinuclear antibodies and more specifically antidouble-stranded DNA indicates SLE. Since the disease is multifactorial and its phenotypes are highly heterogeneous, there is a need to identify multiple noninvasive biomarkers for SLE. Lack of validated biomarkers for SLE disease activity or response to treatment is a barrier to the efficient management of the disease, drug discovery, as well as development of new therapeutics. Recent studies with gene knockout mice have suggested that membrane-bound complement regulatory proteins (CRPs) may critically determine the sensitivity of host tissues to complement injury in autoimmune and inflammatory disorders. Case-controlled and follow-up studies carried out in our laboratory suggest an intimate relation between the level of DAF, MCP, CR1, and CD59 transcripts and the disease activity in SLE. Based on comparative evaluation of our data on these four membrane-bound complement regulatory proteins, we envisaged CR1 and MCP transcripts as putative noninvasive disease activity markers and the respective proteins as therapeutic targets for SLE. Following is a brief appraisal on membrane-bound complement regulatory proteins DAF, MCP, CR1, and CD59 as biomarkers and therapeutic targets for SLE.

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  1. Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Nibhriti Das, Bintili Biswas & Rohan Khera

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  1. Nibhriti Das
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  2. Bintili Biswas
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  1. Medicine, University Of Pennsylvania Department Of Pathology Laboratory Of, Philadelphia, Pennsylvania, USA

    John D. Lambris

  2. University of Colorado School of Medicin, Aurora, Colorado, USA

    V. Michael Holers

  3. Department of Pathology & Laboratory Med, University of Pennsylvania School of Med, Philadelphia, Pennsylvania, USA

    Daniel Ricklin

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Das, N., Biswas, B., Khera, R. (2013). Membrane-Bound Complement Regulatory Proteins as Biomarkers and Potential Therapeutic Targets for SLE. In: Lambris, J., Holers, V., Ricklin, D. (eds) Complement Therapeutics. Advances in Experimental Medicine and Biology, vol 735. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4118-2_4

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