Background Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are both characterised by alterations within T-cell subsets. Studies on the impact of biologic therapies, especially of IL6-receptor-antagonists (IL6ra) on this phenotype are limited. We aimed to characterise the T cell repertoire of patients on long-standing biologic treatment and to compare it with that of therapy-naive patients and those with short term anti-TNF treatment.
Materials and methods We enrolled 92 RA patients, (30 anti-TNF responders, 43 IL6R-antagonist responders and 19 secondary anti-TNF non-responders); and 22 AS patients (15 anti-TNF-responders and 7 non-responders) after at least 6 months of biologic therapies, and 10 healthy controls. The T cell phenotype was assessed with the measurement of 11 cell surface markers with flow cytometry.
Results In both diseases, patients on long term biologic therapy had decreased proportions of CD4/CD45RA+, CD8CD45RA+ naive T cells and increased frequencies of CD8CD45RO+ memory T cells and Th17 cells. HLA-DR, CD25 and CD69+ activated cell subset prevelences were also increased in certain groups as compared with healthy controls. Treg prevalence has normalised as compared with baseline (before the initiation of biologic therapy) in all patient groups. There were some remarkable differences between IL6ra responders and anti-TNF responders as well (e.g.: Th2, CD69, HLADR prevalence). Most of the changes have become evident only after long-term follow up. In RA, a CD4CD69+ cell percentage <2,43 at baseline predicted a good response to anti-TNF treatment.
Conclusions Our findings have provided comprehensive information regarding the profound and diverse long term impacts of biological therapies on CD4+ and CD8+ cell distributions in both RA and AS. Although most of the patients had inactive disease, the T cell repertoire after long-standing biological therapy reflects an activated T-cell phenotype. CD4CD69 has been found as a predictive marker of therapeutic response and may help in treatment choice in agreement with the treat-to-target principle in RA.
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