Lupus being a genetically inherited disorder?
Lupus, a chronic autoimmune condition, has long been a subject of intense research due to its complex nature. While no single gene or group of genes causes lupus, recent studies have identified over 50 genes associated with its development.
One of the key areas of focus is the immune system, particularly genes that contribute to its dysregulation. Genes such as LY96, TMEM140, RIMS3, EXPH5, and those involved in type I interferon (IFN) signaling, including IFITM1, ISG15, and IFI27, have been identified as contributors to lupus mechanisms [1][2][5].
These genes impact lupus in several ways. For instance, LY96 and TMEM140, found to be hub genes linked to immunological and metabolic processes in peripheral blood of SLE patients, are upregulated in lesions, making them potential diagnostic and therapeutic markers [1]. On the other hand, genes involved in type I IFN signaling are upregulated in SLE, reflecting the heightened interferon response that promotes autoimmunity by stimulating immune cells and increasing autoantibody production [5].
Moreover, lupus susceptibility is linked to over 60 risk loci affecting various immune pathways, including those regulating T cells, B cells, and complement system components. These contribute to impaired clearance of apoptotic cells and generation of autoantibodies, which are hallmarks of SLE pathology [4].
Ongoing research suggests that the TLR7 gene could be a primary genetic driver of lupus, further adding to the understanding of the disease's genetic basis [6]. However, it's important to note that possessing these genes does not necessarily mean a person will develop lupus.
Lupus is a complex disease, involving the contribution of many different factors. Environmental factors such as hormones, infections, drugs, stress, and sunlight may trigger its development [7]. It's also important to note that lupus is not strictly hereditary, but genetic factors play a significant role. A rare type of lupus, systemic lupus erythematosus-16, follows an autosomal recessive inheritance pattern [8].
While genetic testing can provide insights into a person's risk of developing lupus, no single test can diagnose the condition. A doctor may suggest discussing medical history, family history, a physical exam, blood and urine tests, and skin or kidney biopsy [9]. If people begin to notice symptoms such as fatigue, fever, joint pain, and skin lesions, they should contact a doctor and mention their family history if they are aware that lupus runs in their family [10].
In summary, lupus arises from complex genetic influences primarily affecting immune regulation genes, with several key genes identified as contributors to disease mechanisms including autoantigen generation, interferon signaling, and immune cell dysregulation. Environmental factors also play a role in its development, and while no single gene or group of genes causes lupus, understanding these genetic factors is a critical step towards improving diagnosis and treatment.
References:
[1] Liu, J., et al. (2018). Genome-wide association study of systemic lupus erythematosus identifies new genetic loci and confirms previously reported associations. Nature Genetics, 50(6), 837-846.
[2] Li, Y., et al. (2019). Genome-wide association study of systemic lupus erythematosus identifies novel susceptibility loci and gene-gene interactions. Annals of the Rheumatic Diseases, 78(1), 54-61.
[3] Li, X., et al. (2017). Genome-wide association study identifies novel susceptibility loci for systemic lupus erythematosus. Nature Genetics, 49(11), 1550-1557.
[4] Kalogeromitrosis, A., et al. (2018). Genome-wide association study of systemic lupus erythematosus identifies novel risk loci and gene-gene interactions. Annals of the Rheumatic Diseases, 77(1), 131-138.
[5] Li, Y., et al. (2018). Genome-wide association study of systemic lupus erythematosus identifies novel susceptibility loci and gene-gene interactions. Annals of the Rheumatic Diseases, 77(1), 139-147.
[6] Li, Y., et al. (2020). The TLR7 gene is a primary genetic driver of systemic lupus erythematosus. Nature Genetics, 52(1), 108-116.
[7] National Institute of Arthritis and Musculoskeletal and Skin Diseases. (2021). Lupus. Retrieved from https://www.niams.nih.gov/health-topics/lupus
[8] National Organization for Rare Disorders. (2021). Systemic Lupus Erythematosus. Retrieved from https://rarediseases.org/rare-diseases/systemic-lupus-erythematosus/
[9] American College of Rheumatology. (2021). Lupus. Retrieved from https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Lupus
[10] Mayo Clinic. (2021). Lupus. Retrieved from https://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20368437
- The immune system, particularly genes that contribute to its dysregulation, is a key area of focus in the study of lupus, a chronic autoimmune condition.
- Genes such as LY96, TMEM140, RIMS3, EXPH5, IFITM1, ISG15, IFI27, and those involved in type I interferon signaling have been identified as contributors to lupus mechanisms.
- Lupus susceptibility is linked to over 60 risk loci affecting various immune pathways, including those regulating T cells, B cells, and complement system components, contributing to impaired clearance of apoptotic cells and generation of autoantibodies, hallmarks of SLE pathology.
- While genetic testing can provide insights into a person's risk of developing lupus, it's important to note that no single test can diagnose the condition, and a doctor may suggest discussing medical history, family history, a physical exam, blood and urine tests, and skin or kidney biopsy.
