Risk factors for developing SLE

What are some risk factors for developing SLE?

As with most autoimmune diseases, SLE probably occurs from a genetic predisposition (two-third of risk) with environmental influences (one-third of risk).

  • a) Environmental: tobacco, viral infection (Epstein–Barr virus [EBV], cytomegalovirus [CMV], and others), silica exposure, ultraviolet (UV) light, pesticides, gut microbiome, and demethylating drugs.
  • b) Genetic: Risk of SLE increases with affected family members, notably first-degree relatives and identical twins. SLE is likely polygenetic which helps explain its varied disease manifestations.
    • • Family aggregation studies show an increased risk when family members have the disease:
      • – Monozygotic twin concordance for SLE: 24% to 35%
      • – Dizygotic twin concordance for SLE: 2% to 5%
      • – First-degree relatives with family history of SLE have a 16-fold increased risk of developing SLE (4%–8%) and a 5-fold increased risk of developing any other autoimmune disease.
    • • Histocompatibility complex (HLA) DR2 ( DRB1∗1501 ) and DR3 ( DRB1:0301 ) increase the relative risk of SLE two to three fold. The presence of these genes may allow more efficient presentation of self-antigens to self-reactive T and B cells.
    • • Complement component deficiencies (C1q, C2, and C4) increase the risk of SLE 5–10-fold presumably due to defective clearance of apoptotic debris and production of interferon (IFN) alpha.
    • • There are a large number of other genetic risk loci (>90) identified in genome-wide association studies that each confer modest risk (odds ratio <2x) for SLE. The non-major histocompatibility complex genes are more likely to be regulatory than effector genes. These include genes involved in aberrant clearance of nuclear material (e.g., CRP, Fc γ receptors IIa and IIIa ITGAM), excessive innate immune activation (e.g., Type I IFNs, IRF5, IRF7, TNFAIP3, TREX1), and abnormal T and B cell activation/signaling (e.g., STAT4, PTPN22, PCDCD1, BLK, BANK1).
    • • It is estimated that it takes 10 to 20 genetic risk alleles to predispose a patient to develop SLE. The more risk alleles a person has, the earlier the onset and more severe the disease will be. Epigenetic effects on the different risk alleles likely account for different disease manifestations and severity.
  • c) Gender/hormonal:
    • • SLE is approximately 10 to 15 times more common in women of childbearing age as than in men. Some predisposing genes are located on the X chromosome (IRAK1, MECP2, and TLR7).
    • • Interestingly, men with Klinefelter’s syndrome (47 XXY) have a 14-fold risk of SLE.
    • • SLE is rare in Turner’s syndrome (XO).
    • • Androgenic medication such as dehydroepiandrosterone (DHEA) has been used to treat SLE.

Sign up to receive the trending updates and tons of Health Tips

Join SeekhealthZ and never miss the latest health information

Scroll to Top