Background/Purpose: IFNє and IFNκ are members of the type-I IFN family that also consists of 12 IFNα subtypes, IFNβ, and IFNω. IFNє and IFNκ share approximately 35% sequence identity with each other and the other 14 IFN proteins. In contrast, IFNα subtypes and IFNω share 60%-95% sequence identity. The role of human IFNє and human IFNk in autoimmune disease in general, and SLE in particular, is unknown. However, the unique expression of IFNє in vaginal tissues, and IFNκ in the skin, are consistent with the sex bias and extensive cutaneous manifestations of lupus. Work to understand the role of IFNє/κ in SLE has been hampered by a paucity of quality reagents for biochemical and biological analysis. To overcome this problem, we have produced and purified human IFNє and IFNκ from E. coli for biochemical and functional studies.

Methods: The IFNs were expressed, refolded, and purified from E.coli, and characterized using SDS-PAGE gel electrophoresis, mass spectrometry, surface plasmon resonance, gene expression using reporter cells lines and PCR, and ELISAs performed using serum for Lupus patients.

Results: Purified IFNє and IFNκ bind to the IFNAR receptors and induce reporter cell gene activation. Gene expression induced by IFNє, or IFNκ, was neutralized by anti-IFNAR neutralizing antibodies, but not by the anti-IFNα neutralizing antibodies examined. IFNє and IFNκ both induced a type-I IFN gene signature in human whole blood. ELISA studies suggest serum from some SLE patients contain antibodies that recognize IFNє or IFNκ.

Conclusion: Taken together, these data suggest IFNε and IFNκ may be contributing to the dysregulated type-I IFN environment observed in some lupus patients, making them putative targets for anti-IFN therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/production-and-characterization-of-human-interferon-epsilon-and-interferon-kappa-to-investigate-their-potential-role-in-lupus/