Background: Psoriatic Arthritis (PsA) is a complex immune-mediated disease. TNF inhibitors (TNFi) are the first-line biologic drugs to treat PsA, targeting soluble TNF-α (sTNF) and membrane-bound TNF-α (mTNF). TNFi are effective for about 60% of patients. We hypothesize that patients’ responses to TNFi depends on their immunophenotype, and that the proportions of mTNF-expressing cells may influence response to TNFi.
Objectives: To identify cell immunophenotypes associated with greater responses to TNFi, and to verify if the proportion of mTNF+ cells forms a potential biomarker of response in PsA.
Methods: Blood from 18 PsA patients was sampled before and 6 months after starting TNFi injections. The populations of T helper (Th) cells, monocytes and mTNF+ cells were determined with flow cytometry using side and forward scatter, and CD3, CD4, CD183, CD196, CD25, CD127, HLA-DR, CD38 and mTNF antibodies. Response at 3 and 6 months after TNFi was monitored using the PsARC scores. Patients were classified as full responders (responders with 0 Tender Joint Score (TJS) and 0 Swollen joint Score (SJS)), weak responders (responders with TJS and SJS) or non-responders.
Results: Potential biomarkers measured at baseline: Three months after TNFi, baseline proportions of Th1 cells were higher in the full responder group compared to the non-responder and weak-responder groups (p = 0.028, Figure 1). Baseline proportions of Th17 cells were lower in the full responder group, baseline proportions of Tregs were higher in the weak responder group. Baseline proportions of monocytes were significantly higher in the non-responder group than in the full responder group (p = 0.027) and the weak responder group (p = 0.022). The ratio Th1/Th17 cells was higher in the full responder group than in the non-responder and weak-responder groups (p = 0.048). Baseline proportions of mTNF+ monocytes and lymphocytes were higher in the responder groups than in the non-responder group. Six months after TNFi, the same trend was found for Tregs, monocytes and mTNF+ lymphocytes but not for Th1 cells, Th17 cells and mTNF+ monocytes.Percentage increase or decrease of potential biomarkers from baseline to 6 months: The percentage increase of Th1 cells and Tregs from baseline to 6 months was higher in the full responder group than in the other groups (Table 1). The percentage increase of Th17 cells and activated (act) cells was higher in the non-responder group than in the weak responder group (act Th1 cells: p = 0.008, and act Th17 cells: p = 0.003) and in the full responder group (act Th1 cells: p = 0.006, and act Th17 cells: p < 0.001). The percentage decrease of monocytes was higher in the full responder group than in the other groups. The percentage increase of Th1/Th17 cells was higher in the full responder group than in the non-responder group (p = 0.017). The percentage of mTNF+ cells decreased in the non-responder group and increased in the weak responder group.
Conclusion: High proportions of Th1 and mTNF+ cells, and low proportions of Th17 cells and monocytes, were identified as potential biomarkers of short-term response to TNFi. However, immunophenotypes seemed to change overtime. Weak responders at 3 months can become full responders or non-responders at 6 months and more. Additional later measurements of proportions of T helper cells, monocytes and mTNF+ cells may predict future relapse or remission of patients with a weak short-term response and help further clinical decision-making.