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Review
. 2017 Jan;69(1):1-12.
doi: 10.1007/s00251-016-0961-7. Epub 2016 Dec 8.

Lupus pathobiology based on genomics

Mohammad Saeed  1
Affiliations
Review

Lupus pathobiology based on genomics

Mohammad Saeed. Immunogenetics. 2017 Jan.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder with complex genetic underpinnings. This review attempts to assemble the myriad of genomic findings to build a clearer picture of the pathobiology of SLE to serve as a guide for therapeutics. Over 100 genes are now known for SLE, and several more penetrant ones have led to the emergence of more defined lupus phenotypes. Also discussed here are the targeted therapies that have come up on the horizon and the specific biologic mechanisms of more traditional therapies which have only recently been explored. The diagnostic toolbox has been enhanced by the addition of new antibodies, gene expression signatures, and mutation panels. This provides an opportunity to piece together the lupus puzzle and even revisit the clinical classification of SLE.

Keywords: Genomics; Immunology; Lupus; Therapeutics.

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Conflict of interest statement

None. Funding None.

Figures

Fig. 1
Fig. 1
SLE pathobiology based on genomic findings. SLE initiation: aberrant apoptosis triggered by dysfunctional DNAses/RNAses activate the endosomal TLR, MDA5, and related pathways in pDCs. Inherent B-cell dysfunction and HLA-associated thymic T-cell negative selection may result in autoantibody formation. SLE potentiation: increased IFN-α, dysfunctional antigen presentation by pDCs, and inherent malfunctioning of T- and B-cells leading to a proinflammatory milieu causes persistent tissue inflammation. Consequent organ damage is exacerbated by defective IC clearance
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