Cellular phenotyping of immune cells in lymph node biopsies during health and different phases of rheumatoid arthritis

This thesis describes the results of characterization and quantification of different immune cells in lymph node biopsies obtained from healthy individuals, individuals at risk for developing RA and early RA patients. We were able to identify differences in the earliest stages of RA in cell types that are involved in autoantibody production and regulating inflammation. Individuals with an increased risk for developing RA showed a decreased capacity of ex vivo pro-inflammatory cytokine production to the same extend as in RA patients compared with healthy individuals, suggesting that an ongoing activation of these pro-inflammatory cells is already present in this pre-clinical phase.
In addition to the finding described above we detected differences in B cell frequencies in the lymph nodes of patients with RA after B cell depleting therapy with rituximab when compared with B cell frequencies in the peripheral blood of these patients. Our findings suggest that memory B cells reside and are not fully depleted in the lymph nodes after treatment, which can lead to the recurrence of signs and symptoms after repopulation of the pathogenic B cells and plasma cells in blood.
Future studies of cells originating from lymph nodes can reveal crucial information to better understand the pathogenesis of RA which will be fundamental to develop novel approaches for treatment and potentially cure or prevention of RA.