Systematic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs and tissues. It is a relatively rare disease, with a prevalence rate of approximately 50 to 100 cases per 100,000 individuals.

SLE is more common in women than men, and it usually occurs in individuals between 15 and 45 years of age. The diagnosis of SLE is challenging, as it often mimics other diseases, and it depends on clinical and laboratory criteria. The pathogenesis of SLE is complex and involves genetic, epigenetic, environmental, hormonal, and immunologic factors.

Despite advances in therapy, SLE remains a challenging disease to manage, and patients suffer from a range of complications that affect their quality of life.

New therapeutic targets for SLE

Developing new therapeutic targets for SLE is a major challenge, as the immune dysregulation in SLE is complex and multifactorial. However, emerging data suggest that several potential targets can be exploited for SLE therapy.

Here are ten exciting therapeutic targets for SLE:.

1. Targeting interferons

The expression of type I interferon (IFN) is increased in the sera and tissues of patients with SLE. Multiple lines of evidence suggest that type I IFNs are critical in the pathogenesis of SLE.

Type I IFNs promote the production of autoantibodies, the activation of dendritic cells and T-cells, and the development of lupus nephritis. Therefore, targeting type I IFNs is a promising therapeutic strategy for SLE. Several drugs that target type I IFNs are currently in development, including sifalimumab and anifrolumab.

2. Targeting B-cells

B-cells are central players in the pathogenesis of SLE. B-cells produce autoantibodies, activate T-cells, and promote the development of immune complexes that deposit in organs and tissues.

Therefore, targeting B-cells is a logical approach to SLE therapy. Several drugs that target B-cells are currently in use or development, including rituximab, belimumab, and atacicept.

3. Targeting T-cells

T-cells play an important role in the pathogenesis of SLE by promoting the production of autoantibodies and the development of lupus nephritis. Therefore, targeting T-cells is a promising approach to SLE therapy.

Several drugs that target T-cells are currently in use or development, including abatacept, tocilizumab, and ustekinumab.

4. Targeting cytokines

Cytokines are critical mediators of the immune system, and their imbalance contributes to the pathogenesis of SLE. Therefore, targeting cytokines is an attractive approach to SLE therapy.

Several drugs that target cytokines are currently in use or development, including infliximab, adalimumab, anakinra, canakinumab, and secukinumab.

5. Targeting chemokines

Chemokines are small molecules that recruit immune cells to sites of inflammation. Several chemokines are involved in the pathogenesis of SLE, including CXCL10, CXCL13, CXCL8, and CCL2.

Therefore, targeting chemokines is a promising approach to SLE therapy. Several drugs that target chemokines are currently in development, including anti-CXCL10 and anti-CCR2.

6. Targeting Toll-like receptors

Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns and promote inflammation.

TLRs are involved in the pathogenesis of SLE, as their activation leads to the production of type I IFNs and the activation of B-cells and T-cells. Therefore, targeting TLRs is a potential approach to SLE therapy. Several drugs that target TLRs are currently in development, including IMO-8400 and MEDI9197.

7. Targeting complement

The complement system is an important component of the innate immune system, and its activation leads to the production of inflammatory mediators and the destruction of pathogens and cells.

However, complement dysregulation is involved in the pathogenesis of SLE, as its activation leads to tissue damage and inflammation. Therefore, targeting complement is a potential approach to SLE therapy. Several drugs that target complement are currently in development, including eculizumab and AMY-101.

8. Targeting epigenetic modifications

Epigenetic modifications are changes in the DNA and histones that regulate gene expression.

Epigenetic modifications play an important role in the pathogenesis of SLE, as they regulate the expression of genes involved in immune function and inflammation. Therefore, targeting epigenetic modifications is a potential approach to SLE therapy. Several drugs that target epigenetic modifications are currently in development, including azacitidine and vorinostat.

9. Targeting microRNAs

MicroRNAs are small non-coding RNAs that regulate gene expression by targeting messenger RNAs. Several microRNAs are involved in the pathogenesis of SLE, as they regulate the expression of genes involved in immune function and inflammation.

Therefore, targeting microRNAs is a potential approach to SLE therapy. Several drugs that target microRNAs are currently in development, including miRagen’s MRG-201 and Mirum’s MIR106b-25 inhibitor.

10. Targeting gut microbiota

The gut microbiota is a complex ecosystem of microorganisms that regulate immune function and metabolism.

Dysbiosis, or disruption of the gut microbiota, is involved in the pathogenesis of SLE, as it leads to the translocation of bacteria and toxins and the activation of immune cells. Therefore, targeting gut microbiota is a potential approach to SLE therapy. Several drugs that target gut microbiota are currently in development, including FMT (fecal microbiota transplantation) and modified pro- and prebiotics.

Conclusion

SLE is a complex and multifactorial disease that requires a holistic and personalized approach to therapy. The development of new therapeutic targets for SLE is critical, as current therapies have limited efficacy and cause significant side effects.

The ten therapeutic targets discussed in this article represent exciting progress in the field of SLE therapy, and they offer hope for patients who suffer from this devastating disease.