Genetic lupus-like syndrome [82 genes]

The set of genes includes those whose genetic defects can be sufficient cause autoimmune diseases that show overlapping characteristics with systemic lupus erythematosus or localised lupus.

Among the molecular mechanisms that cause this group of pathologies there are genes encoding the classical complement pathway, complement regulators and some of the alternative pathway that are related to glomerulonephritis; genes involved in DNA repair processes, whose loss of function is prone to developing high titres of ANA, anti-dsDNA, anti-histone and anti-Ro autoantibodies (DNASE1, DNASE1L3, TREX1, RNASEH2A/B/C); genes related to interferonopathies (TMEM173, IFIH1, SAMHD1); signal transducer genes involved in STAT pathways and regulators of TLR-mediated signals (STAT1, STAT4, TLR5, TLR7, BANK1, BLK); genes whose defects lead to the development of primary immunodeficiencies with susceptibility to autoimmune conditions and overlapping characteristics with lupus (PRKCD, CTLA4, NCF2, CYBB, RAG2, IKZF1, TYK2…); or genes encoding TNF-mediated proinflammatory receptors and regulators (TNFAIP3, IRF5, IRF7…).

• Lupus perniosis
• Vasculitis
• Arthralgia
• Chronic autoinflammation
• Lupus-like symptoms
• Multisystemic manifestations

• Rare monogenic forms: unknown
• SLE: ~0.5% of general population

• Diagnosis and genetic counseling
• Anti-inflammatories
• Immunosuppressants
• Monoclonal antibodies
• Immunomodulators

Identifying a genetic defect responsible for the disease would allow a precise molecular diagnosis to be issued and make it possible to provide genetic counseling to the patient and their family members. In some cases, detecting a genetic variant can help explore specific treatment options.

Not all cases diagnosed with SLE are susceptible to genetic study because it is an autoimmune disorder of multifactorial origin. In those cases in which “lupus-like” is suspected, or there is an early presentation with severe expression, there may be an intrinsic genetic cause causing the disease.