Systemic lupus erythematosus (SLE) is associated with increased expression of genes regulated by Type I interferon (IFN) in 50–70% of patients.¹ Previous studies, including our own, have demonstrated the requirement for a precisely regulated IFNα response in driving the differentiation of immature B cells into plasma cells, which generate antibodies during viral infections, as well as regulatory B cells (Bregs) that promote immune homeostasis.^{2 3}

Chronic IFNα production in SLE contributes to autoimmunity through several mechanisms including: (1) promoting the differentiation of monocytes to dendritic cells, leading to the activation of autoreactive T cells; (2) favouring the generation of effector and memory CD8+ T cells, further amplifying the autoimmune response; and (3) skewing B cell differentiation towards autoantibody-producing plasma cells, but not Bregs.¹

This presentation will review our latest research findings on the relevance of neutralizing natural autoantibodies against IFNα (anti-IFN-Abs) in spontaneously improving SLE pathogenesis by restoring B cell homeostasis, including Bregs. The evidence highlights the importance of measuring neutralizing anti-IFN-Abs as clinical assessment parameters before initiating treatment.

References

1. Bradford HF, Haljasmägi L, Menon M, et al. Inactive disease in patients with lupus is linked to autoantibodies to type I interferons that normalize blood IFNα and B cell subsets. Cell Rep Med. 2023;4(1):100894. doi: 10.1016/j.xcrm.2022.100894.

2. Jego G, Palucka AK, Blanck JP, et al. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity. 2003;19(2):225–34. doi: 10.1016/s1074-7613(03)00208-5.

3. Menon M, Blair PA, Isenberg DA, et al. A regulatory feedback between plasmacytoid dendritic cells and regulatory B cells is aberrant in systemic lupus erythematosus. Immunity. 2016;44(3):683–97. doi: 10.1016/j.immuni.2016.02.012.

Learning Objectives At the end of this presentation participants will be able to:

• Describe the association between SLE and Type I IFN expression

• Explain the role of IFNα in B cell differentiation, including both plasma cells and Bregs

• Discuss the potential therapeutic role of neutralizing natural autoantibodies against IFNα (anti-IFN-Abs) in SLE

• Explain the significance of measuring anti-IFN-Abs as a clinical assessment parameter in SLE patients