The paradigm that autoimmune diseases are abberations in the adaptive immune system is over 50 years old, but recent data suggest a multitude of abnormalities in the innate immune system in lupus and other autoimmune diseases. This viewpoint elaborates the reasons that I think it is time to reexamine this paradigm and shift our research focus to the innate immune system in lupus and other prototypic autoimmune diseases.
CrispínJCLiossisS-NCKis-TothK, et al. Pathogenesis of human systemic lupus erythematosus: recent advances. Trends Mol Med2010; 16: 47–57.
2.
MiyaderaHTokunagaK. Associations of human leukocyte antigens with autoimmune diseases: challenges in identifying the mechanism. J Hum Genet2015; 60: 697–702.
3.
GrahamRRHomGOrtmannW, et al. Review of recent genome–wide association scans in lupus. J Int Med2009; 265: 680–688.
4.
HerradaAAEscobedoNIruretagoyenaM, et al. Innate immune cells’ contribution to systemic lupus erythematosus. Front Immun2019; 10: 772.
5.
ElliottDESiddiqueSSWeinstockJV. Innate immunity in disease. Clin Gastroenterol Hepatol2014; 12: 749–755.
6.
Westwell-RoperCNiemietzITuckerLB, et al. Periodic fever syndromes: beyond the single gene paradigm. Pediatr Rheumatol Online J2019; 17: 22.
7.
PatinE. Plague as a cause of familial mediterranean fever. Nat Immun2020; 21: 833–834.
8.
PsarrasAEmeryPVitalEM. Type 1 interferon-mediated autoimmune diseases: pathogenesis, diagnosis, and targeted therapy. Rheumatology2017; 56: 1662–1675.
9.
SmattiMKCyprianFSNasrallahGK, et al. Viruses and autoimmunity: a review and potential interaction and molecular mechanisms. Viruses2019; 11: 762.
10.
HarleyJBChenXPujatoM, et al. Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity 2018. Nat Genet2018; 50: 699–707.
11.
TsoiLCHileGABerthierCC, et al. Hypersensitive interferon response in lupus keratinocytes reveal key mechanistic determinants of cutaneous. Lupus J Immun2019; 202: 2121–2130.
12.
FurieRKhamashtaMMerrillJT, et al. Anifrolumab, an anti-interferon alpha receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arth Rheum2017; 69: 376–386.
13.
WandlUBNagel-HiemkeMMayD, et al. Lupus–like autoimmune disease induced by interferon therapy for myeloproliferative disorders. Clin Immun Immunopath1992; 65: 70–74.
14.
RamantaniGKohlhaseJHertzbergC, et al. Expanding the phenotypic spectrum of lupus erythematosus in aicardi–goutieres Syndrome. Arth Rheum2010; 62: 1469–1477.
15.
SouyrisMCenacCAzarP, et al. TLR7 Escapes X chromosome inactivation in immune cells. Sci Immunol2018; 3: 1–10.
16.
ChenMDahaMRKallenbergCG. The complement system in systemic autoimmune disease. J Autoimmun2010; 34: J276–J286.
17.
KaplanMJ. Role of neutrophils in systemic autoimmune diseases. Arthritis Res Ther2013; 15: 219–240.
18.
GuptaSKaplanMJ. The role of neutrophils and NETosis in autoimmune and renal diseases. Nat Rev Nephrol2016; 12: 402–413.
19.
HoangTKAlbertDAAlbertDA. Novel presentations of periodic fever syndromes: discrepancies between genetic and clinical diagnoses. Eur Jour Rheum2019; 6: 12–18.
