How similar are these conditions to Rheumatoid Arthritis? Does this suggest a role for lack of PDL1 ligand on target joint cells and/or insufficient PD-1 signalling on Tcells in the joints (too much soluble PD1?) as drivers of RA, since blocking PD-1 receptor signalling in cancer treatment causes similar conditions to manifest as side effects? 

Has the role of PD-1 expression in RA disease pathology been directly studied?

-Does the increased soluble PD-1 and the lack of its ligands (soluble PDL1 and PDL2) in joint biopsies of SpA suggest a lack of PD-1 signaling to shut off T cells could be a driver of Spondyloarthritis? Could a PD-1 agonist be a potential treatment for SpA?

- How similar is SpA to RA or how relevant might this data be to RA?  

- Is IL17A also important in RA disease pathology?

- Would a PD-1 receptor agonist be useless if the soluble PD-1 is actually responsible for signalling into IL17a production and not merely serving as a bystander to PD-1 receptor expression and not merely causing saturation of PD-1's ligands? 

Does soluble PD-1's independent activity in cell culture inducing IL17a suggest a unique role for the soluble protein that can't be addressed by an agonist hitting PD-1 in its cell-surface-expressed / receptor format on T cells? Or would shutting off these T cells be more important than whatever the soluble PD-1 may be doing?

-POS0497 Shows higher soluble PD1 and elevated PD1 expressing t cells in the joints in JIA (juvenile idiopathic arthritis). Would higher soluble PD1 magnify t cell activity by binding to PD1's ligands (PDL1) like a decoy receptor, thus freeing the T-cell-expressed surface PD1 from any deactivation signal, and letting T cells run amok?

-POS0166 is another study suggesting that plasma PD1 is elevated in JIA. 

-Could a PD1 agonist solve this problem and shut off those cells in JIA?

-Could a PD1 agonist solve this problem and shut off those cells in JIA?