Immunosenescence and juvenile idiopathic arthritis

Immune Aging and Autoimmune Diseases in Children

“…So far, it is not clear which of the two theories should be supported: the first, favoring premature immunosenscence in childhood-onset autoimmunity as the primary defect causing breakdown of self-tolerance; the second, that premature immunosenescence in children with autoimmune disorders is secondary to chronic stimulation and activation of the immune system by inflammatory processes of the autoimmune disease itself [14,[130][131][132][133]. For the design of targeted therapy and preventive strategies, it is necessary to have an insight into the pathogenetic factors which lead to the breakdown of selftolerance and perpetuation of inflammation [14]. In this context, population-based longitudinal studies on risk factors for development of autoimmunity beginning at infancy are indispensable.…”

“…There are two explanations for reduced frequency of TRECs: first, reduction by diminution of thymic production, thus individuals susceptible to RA would enter adulthood with less thymic activity; second, reduction by a history of increased peripheral turnover in the naive T cell compartment [14]. It has been suggested that the maintenance of the peripheral T cell homeostasis is overtaken by compensatory replication of peripheral mature T cells [9,76].…”

“…This prompted speculations as to whether children with autoimmune diseases have a prematurely aged immune system setting them at risk of developing autoimmunity. It has been argued that studies investigating patients with autoimmune diseases measure only the peripheral and local consequences of autoimmune T cell clones on peripheral T cell homeostasis under decreased thymic function or inflammatory activity and can therefore only describe the alterations of an already affected immune system [14]. No conclusions, however, can be drawn from these data on immunological alterations preceding the onset of the autoimmune diseases studied.…”

“…Reduced telomere length of peripheral T cells was interpreted as a sign of replicative exhaustion in RA patients. A highly restricted T cell receptor (TCR) repertoire was found at sites of inflammation and in peripheral lymphoid organs [14].…”

The Etiology of Juvenile Idiopathic Arthritis

“…The "Suspected" Infectious Agents Autoimmunity can be triggered by many environmental factors, infectious agents above all, and molecular mimicry is the strongest pathogenetic mechanism, combined with increased immunogenicity following infections and polyclonal lymphocyte activation [14,[30][31][32]. Clinical observations have shown that JIA can follow an infectious disease caused by viruses and bacteria, referred as potential triggers.…”