Examples include variants of TLR4 in sepsis, malaria, inflammatory bowel disease and atherosclerosis; variants in TLR2 in tuberculosis and asthma; a variant in Mal (a key signal for TLR2 and TLR4) in malaria, tuberculosis and systemic lupus erythematosus; and variants in the kinase IRAK4 in pyogenic infections.
The IRAK4i I92 exhibits a broader inhibitory effect than HCQ on proinflammatory pathways triggered by RNA-IC, suggesting IRAK4 inhibition as a therapeutic option in SLE.
Lastly, BMS-986126 inhibited TLR7- and TLR9-dependent responses using cells derived from lupus patients, suggesting that inhibition of IRAK4 has the potential for therapeutic benefit in treating lupus.