Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression

Abstract

Patients with rheumatoid arthritis (RA) develop features of accelerated ageing, including immunosenescence. These changes include decreased thymic functionality, expansion of late-differentiated effector T cells, increased telomeric attrition, and excessive production of cytokines (senescence-associated secretory phenotype). The progression of RA has been associated with the early development of age-related co-morbidities, including osteoporosis, cardiovascular complications, and cognitive impairment. Here I review data supporting the hypothesis that immune-senescence contributes to the aggravation of both articular and extra-articular manifestations. Of note, poor cognitive functions in RA were associated with senescent CD28-T cells, inflammaging, and autoantibodies against brain antigens. The pathways of immune-to-brain communication are discussed and provide the rationale for the cognitive impairment reported in RA.

Low Dose Radiation Therapy, Particularly with 0.5 Gy, Improves Pain in Degenerative Joint Disease of the Fingers: Results of a Retrospective Analysis

“…This indicates that the involvement of the thumb is more relevant at a younger age, possibly rather by destructive than inflammatory processes resulting from an overuse of the thumb. On the other hand, the positive correlation between the rising age and the involvement of the fingers II-V indicates that the prevalence for systemic inflammatory processes, such as in arthritis, is rising with the age [31]. The here presented results show that patients with involvement of the thumb have a worse therapeutic outcome.…”

Cognitive Decline in Rheumatoid Arthritis: Insight into the Molecular Pathogenetic Mechanisms

“…Overall, these data demonstrated a global cognitive decline in RA patients, which was associated with disease activity and immune differences, thus suggesting that peripheral immune imbalance, along with a proinflammatory milieu, could predict the cognitive deficits in RA. Of note, although the presence of higher BDNF plasma levels could seem unusual in patients with chronic inflammation, such as those with RA, it should be considered that the circulating BDNF might largely be derived from leukocytes in inflammatory diseases [ 90 ]. Interestingly, it has been shown that BDNF is constitutively expressed by peripheral blood mononuclear cells (PBMCs) and synovial cells [ 90 ].…”

“…Of note, although the presence of higher BDNF plasma levels could seem unusual in patients with chronic inflammation, such as those with RA, it should be considered that the circulating BDNF might largely be derived from leukocytes in inflammatory diseases [ 90 ]. Interestingly, it has been shown that BDNF is constitutively expressed by peripheral blood mononuclear cells (PBMCs) and synovial cells [ 90 ]. Instead, GDNF, whose decreased plasma levels were found to be associated with cognitive dysfunctions in RA patients, is produced only in the central nervous system [ 90 ].…”

“…Interestingly, it has been shown that BDNF is constitutively expressed by peripheral blood mononuclear cells (PBMCs) and synovial cells [ 90 ]. Instead, GDNF, whose decreased plasma levels were found to be associated with cognitive dysfunctions in RA patients, is produced only in the central nervous system [ 90 ]. Therefore, decreased levels of GDNF could be a better predictor of worse cognitive performance compared to BDNF [ 90 ].…”

The interplay between immunosenescence and age-related diseases

“…Several features of premature immunosenescence have been observed in RA. These alterations include decreased thymic functionality, expansion of late-differentiated effector T cells, increased telomeric attrition, and increased production of pro-inflammatory cytokines (senescence-associated secretory phenotype) [ 27 ]. A significant expansion of late-differentiated T cells (CD4 + CD28 − and CD8 + CD28 − ) in RA was reported several years ago [ 28 , 29 ], as similarly observed during healthy aging [ 30 ].…”