This year BRITSpA run its third abstract competition. The winner of the certificate and cheque for £500 was Charles Bridgewood (Leeds) who gave an excellent presentation of his work entitled “ An Entheseal Innate Immune Cell Biological basis for differential efficacy of PDE4 and IL-23 pathway blockade between Psoriatic Disease and Rheumatoid Arthritis”.
Noting that both IL-23 and PDE4 inhibition are ineffective in RA but show efficacy in PsA related synovitis despite similar cytokine and molecular profiles between synovitis in both disease settings, the authors hypothesised that enthesis resident innate immune cells, especially myeloid cells, might be capable of IL-23 production that could be modulated by PDE4 pathway blockade. They utilised human entheses (n=6) and myeloid cells (CD14+) from both the adjacent bone and soft tissue fractions. Results from this work showed that aA CD45+/HLADR+/CD14+ myeloid cell population could be isolated from the normal enthesis in both the ST and EB fractions but with a much higher abundance in EB. This purified population from both ST and EB produced IL-23, TNFα and CCL20 following TLR/CLR receptor stimulation. IL-23 and TNFα production wasnegligible in the CD14- fraction. Moreover, IL-23 and TNF induction was inhibited by the PDE4 inhibitor rolipram. In blood derived myeloid cells, rolipram and other cAMPelevating agents (histamine and 8-br-cAMP), also inhibited IL-23 secretion.
The authors concluded that these findings demonstrate that the human enthesis harbours an IL-23 producing myeloid cell population which can be modulated by PDE4 pathway manipulation supporting the idea of an IL-23/17 pathway genetic architecture of SpA in the context of entheseal biology and offering a “reverse translation” explanation for divergent therapeutic pathways between SpA and RA. Read the full abstract here.
