Peripheral Blood Lymphocyte Analysis in Oligo- and Polyarticular Juvenile Idiopathic Arthritis Patients Receiving Methotrexate or Adalimumab Therapy: A Cross-Sectional Study

Abstract

Juvenile idiopathic arthritis (JIA) is an umbrella term for seven distinct chronic immune-mediated diseases. Disease-modifying anti-rheumatic drugs (DMARD) are used to treat the underlying joint inflammation as well as extra-articular manifestations. Immunosuppression is a considerable side effect of the drugs. The main goal of this study was to investigate the effect of different JIA therapies on leukocyte subpopulations, which play a role in immune-defense. Three study groups were established. The first group consisted of JIA patients treated with methotrexate solely, the second one received a combination of methotrexate (MTX) and adalimumab (ADA). The control group was made up of the patients' healthy siblings. A total of 63 children were recruited. Fourty-one children with JIA and 22 healthy controls were included in the study. The absolute number of CD3+ T-cells was significantly elevated in patients treated with biological therapy compared to healthy controls (p2 = 0.017). In contrast, the number of CD56+ natural killer cells was significantly lower in children receiving biological therapy in comparison with healthy donors (p2 = 0.039). A significant alteration was also demonstrated between patients treated with MTX and MTX/ADA group concerning CD 19+ B-cells (p3 = 0.042). This is the first study that demonstrates significant alterations in the number of B-cells and T-cells with a relative decrease of NK-cell ratios in JIA patients receiving different DMARD therapy.Clinical Trial Registration:NCT03833271. 21.01.2019.

B Cells on the Stage of Inflammation in Juvenile Idiopathic Arthritis: Leading or Supporting Actors in Disease Pathogenesis?

“…Overall, the accumulation of memory B cells in the synovia of JIA patients suggests antigen-driven activation of B cells within the inflamed tissues potentially triggered by local antigens ( 18 ). Changes in B cell subpopulations have also been documented in peripheral blood and synovial fluid from JIA patients ( 12 – 14 , 17 , 18 , 92 , 177 – 179 ). Indeed, expansions of CD5+ B cells and transitional (CD24 high CD38 high ) B cells have been reported in oJIA and pJIA patients ( 12 – 14 , 17 ), which suggest that defects in B cell differentiation and homeostasis may occur in JIA.…”

Autoinflammatory Diseases and Cytokine Storms—Imbalances of Innate and Adaptative Immunity

“…This drug, with anti-inflammatory and immunosuppressive functions, also has important collateral effects, especially in pediatric age since it blocks growth, delays bone development, and causes weight gain and mood instability. Therefore, the identification of cytokines as therapeutic targets has great relevance: examples of this are canakinumab and anakinra, inhibitors of soluble IL-1β and its receptor, respectively; infliximab and certolizumab, which bind TNF-α; tocilizumab, which blocks IL-6 ( Table 1 ) [ 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , …”