J Rheum Dis.  2018 Oct;25(4):213-220. 10.4078/jrd.2018.25.4.213.

Monogenic Autoimmune Diseases

• Jeong DC

• KMID: 2429707
• DOI: http://doi.org/10.4078/jrd.2018.25.4.213

Abstract

Monogenic autoimmune diseases (AD) present as lupus-like clinical manifestations with recurrent fever or various vasculopathies. Recurrent fever with an elevation of acute phase reactants and various skin lesions are similar in monogenic AD and autoinflammatory disease. The molecular pathogenesis of adult systemic erythematosus can be understood through monogenic AD based on gene defects: complement, apoptosis, interferonopathy via nucleic acid sensing, tolerance, rasopathies, and others. Skin vasculopathy with chilblains and livedo reticularis, interstitial lung disease, and panniculitis are common occurrences in type I interferonopathy. Some syndromes have been reported to present with autoimmune inflammation and the general clinical findings, including cerebral calcification. Various clinical manifestations in monogenic AD present in accordance with the gene loss- or gain-of-function mutations involved. The monogenic AD for the early onset of more severe lupus-like symptoms or vasculopathy needs to be considered. Furthermore, clinical trials were conducted via targeted therapy for related molecular pathways, because conventional treatments were not effective in managing monogenic AD.

Keyword

Autoimmune diseases; Genes; Systemic lupus erythematosus; Interferon

MeSH Terms

Acute-Phase Proteins
Adult
Apoptosis
Autoimmune Diseases*
Chilblains
Complement System Proteins
Fever
Humans
Inflammation
Interferons
Livedo Reticularis
Lung Diseases, Interstitial
Lupus Erythematosus, Systemic
Panniculitis
Skin
Acute-Phase Proteins
Complement System Proteins
Interferons

Figure

• 

  Figure 1. Type 1 interferon signaling and type 1 interferonopathies as currently assigned. This figure is adapted from Rodero et al. J Exp Med 2016;213:2527-38 [28]. ADAR1: adenosine deaminase RNA specific 1, ACP5: acid phosphatase 5, C1q: complement 1q, cGAS: GMP-AMP synthetase, IFN /: interferon /, IFNAR1: interferon alpha and beta receptor subunit 1, IFNAR2: interferon alpha and beta receptor subunit 2, JAK1: Janus kinase 1, IRF3: interferon regulatory factor 3, IRF9: interferon regulatory factor 9, ISGs: interferon-stimulating genes, ISG15: interferon-stimulating gene 15, MDA5: melanoma differentiation-associated gene 5, MAVS: mitochondrial antiviral signaling 5, POLA1: DNA polymerase 1, PSMB4: proteasome subunit beta 4, PSMB8: proteasome subunit beta 8, PSMA3: proteasome subunit beta 3, RNASEH2A: ribonuclease H2A, RNASEH2B: ribonuclease H2B, RNASEH2C: ribonuclease H2C, RIG-1: retinoic acid inducible gene-1, SAMHD1: SAM domain and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1, SKIV2L: superkiller viralicidic activity 2-like RNA helicase, STAT1: signal transducers and activators of transcription 1, STAT2: signal transducers and activators of transcription 2, TYK2: tyrosine kinase 2.

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