Monogenic Lupus.
OBJECTIVE
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease known for its clinical heterogeneity. Over time, new insights into the complex genetic origin of SLE have started to explain some of this clinical variability. These findings, reviewed here, have also yielded important understanding in the immune mechanisms behind SLE pathogenesis.


RESULTS
Several new monogenic disorders with lupus-like phenotype have been described. These can be organized into physiologic pathways that parallel mechanisms of disease in SLE. Examples include genes important for DNA damage repair (e.g., TREX1), nucleic acid sensing and type I interferon overproduction (e.g., STING, TREX1), apoptosis (FASLG), tolerance (PRKCD), and clearance of self-antigen (DNASE1L3). Further study of monogenic lupus may lead to better genotype/phenotype correlations in SLE. Eventually, the ability to understand individual patients according to their genetic profile may allow the development of more targeted and personalized approaches to therapy.
Division of Immunology, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, USA. Mindy.Lo@childrens.harvard.edu.|Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Mindy.Lo@childrens.harvard.edu.
Mindy S
MS
Lo
D004706:Endodeoxyribonucleases / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics; D053222:Fas Ligand Protein / Q000235:genetics; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics; D051745:Protein Kinase C-delta / Q000235:genetics; D000099197:STING Protein
D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D053222:Fas Ligand Protein; D008565:Membrane Proteins; D010750:Phosphoproteins; D051745:Protein Kinase C-delta; C505661:FASLG protein, human; C532857:STING1 protein, human; D000099197:STING Protein; C497258:PRKCD protein, human; C485421:DNASE1L3 protein, human; C429526:three prime repair exonuclease 1
Monogenic lupus; SLE; Systemic lupus erythematosus; Type I interferon