The cause is unknown. It is thought to be multifactorial involving genetic and environmental elements with female sex strongly influencing pathogenesis (1).
Recognised genetic and epidemiological predisposing factors include:
- hereditary:
- the concordance for identical twins is 30% compared to 5% for other sibs
- complement deficiencies:
- the strongest disease susceptibility genes are those associated with homozygous complement deficiencies (C1q, C1r, C1s, C2 and C4)
- female sex
- female hormones are thought to play an important role although the mechanism is unclear (3)
- associated with HLA-DR2, HLA-DR3 and C4A null complement alleles
- a particular MHC haplotype that is commonly found in Caucasian patients with SLE is (HLA-A1, HLA-B8, HLA-DR3, C4AQ*O); this is often a marker of a subset of the disease that is associated with anti-Ro antibodies
- drugs e.g. hydralazine, procainamide or griseofulvin
- environmental influences
- Epstein–Barr virus (EBV) infection (4)
- ultraviolet light (associated with the presence of the anti-Ro antibody) *(4)
Note:
- *sunlight and ultraviolet light have been thought to be causative factors in development of SLE and of flares but this is not supported by the most recent study (5)
References:
- Costenbader KH, Feskanich D, Stampfer MJ, et al. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum. 2007 Apr;56(4):1251-62.
- Teruel M, Alarcón-Riquelme ME. The genetic basis of systemic lupus erythematosus: what are the risk factors and what have we learned. J Autoimmun. 2016 Nov;74:161-75.
- Barber M et al. The global epidemiology of SLE: narrowing the knowledge gaps. Rheumatology (Oxford). 2023 Apr; 62(Suppl.1): i4–i9.
- Hanlon P, Avenell A, Aucott L, et al. Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and systemic lupus erythematosus. Arthritis Res Ther. 2014 Jan 6;16(1):R3.
- Tanner TI, Agalliu I, Wahezi DM, et al. Relationship of ultraviolet light exposure and cutaneous and systemic disease activity in youth with childhood-onset systemic lupus: Results from the Childhood Arthritis and Rheumatology Research Alliance Registry. Res Sq [Preprint]. 2024 Jan 3:rs.3.rs-37777