Phenotyping immune cells in peripheral blood before and after 4 months of treatment with Methotrexate, TNFa-, or IL17 inhibitors in patients with psoriatic arthritis

INTRODUCTION
Psoriatic Arthritis (PsA) is a chronic immune-mediated inflammatory disease with heterogenous symptoms that affect a variety of structures in a distinct individual way. Symptoms experienced by the individual patient might include clinical manifestations involving skin, joints, entheses, nails, and/or other connective tissues. Nonetheless, patients diagnosed with PsA suffer from the alleged same disease they experience a diverse range of symptoms and manifestations which respond very differently to available treatments.

Current treatment strategies include first line treatment with disease modifying anti-rheumatic drugs (DMARDs) with little and/or unsatisfactory effect in PsA (1-3) . Biological treatment of PsA include Tumor Necrosis Factor α (TNFα) inhibitors and Interleukin 17 (IL-17) inhibitors (4). Nevertheless, 20-30% of PsA patients fail to respond to available biological agents (5, 6) which might be explained by different response to drugs due to different patient- and/or disease specific characteristics as implied in one study of survival rates of TNF inhibitor in patients with two different PsA phenotypes (7). This is demonstrating the importance in comparing the immune pathological findings with patient- and disease specific characteristics and treatment response.
T-cell differentiation with development of the T-cell into specific T-cell phenotypes is believed to play an important role in the immune pathological pathway of PsA (8, 9). While T helper cell type (th) 1 and th17 cells are believed to play a part in development of adaptive autoimmune response and tissue damage in PsA, recent knowledge further implement an innate autoinflammatory response (10). Nevertheless, the association between different T-cell phenotypes in PsA remain unclear and current evidence has also been associating several additional cell types of both innate and adaptive immunity with the developing inflammatory response leading to PsA (8).

Studies on the effect of treatment on human T cell phenotypes is limited. In PsO, TNFα inhibition has shown decreased levels of circulating Th17 cell and reduced Th1 activity (11, 12), while one study showed increased numbers of circulating Th17 cells in patients with inflammatory arthritis (including PsA) during TNFα inhibitor treatment (13). Studies regarding effect of treatment on immune cell phenotypes, including both methotrexate (MTX), IL17 inihibitors (IL17i) and TNFα inhibitors (TNFi), are needed in order to further understand immune pathological mechanisms of PsA. Furthermore, it is important to investigate immune cell phenotypes and associations with different clinical PsA phenotype that might provide knowledge on how to choose between treatments to ensure optimal effect on various symptoms.