Autoimmunity in the Elderly: Insights from Basic Science and Clinics - A Mini-Review

Abstract

Advancements in the field of biomedicine, including the control of infectious diseases through antibiotics and vaccination practices and the prevention of chronic disorders, have led to reduced mortality, increased life expectancy and, as such, growth of the older population. Ageing is accompanied by profound morphological and physiological alterations. In particular, the immune system undergoes a complex series of remodeling/restructuring events, involving almost all compartments - both the innate and the adaptive system. This process is termed immunosenescence or immune dysregulation and, basically, includes 3 events: a reduction in immune response, an increase in the inflammatory and oxidation background (inflammaging and oxi-inflammaging), and a production of autoantibodies. While there is an increase in autoimmunity in the elderly, this does not always translate into an increase in autoimmune diseases, which represent an important cause of morbidity and mortality and affect 5-10% of the world population. Each disease involves a specific age group. Generally speaking, most autoimmune diseases have a decreased peak age of onset, except for very few diseases such as giant cell arteritis and primary biliary cirrhosis, which are more prevalent among the elderly, or inflammatory bowel disease, which has 2 peaks of onset, the first one in young subjects and the other in those older than 60 years. Autoimmune disorders in the elderly have unique clinical presentations, and insidious and atypical symptoms may constitute a challenge for the physician. They are generally milder than in adults and can be controlled by a proper therapeutic treatment. However, despite advancements both in basic and clinical sciences, further studies and investigations are warranted and should be carried out in order to dissect the molecular framework induced by ageing.

DNA Damage Response and Oxidative Stress in Systemic Autoimmunity

“…Moreover, age-related transformations redesign the immune architecture and the balance between pro-inflammatory and anti-inflammatory protective factors, as well as between pro-apoptotic and anti-apoptotic signals. In fact, elderly people experience increased reactivity to autoantigens, loss of tolerance, and systemic inflammation, while at the same time they suffer from degenerative diseases, which, in turn, increase the risk of developing an autoimmune disease [98]. Moreover, epigenetic changes and the increase in inflammatory cytokines and chemokines such as TNF-α, C-reactive protein, IL-8, MCP1, and RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted) that occur in the elderly play a crucial role in the onset of autoimmune diseases [99].…”

Aging, immunosenescense, and very late-onset neuromyelitis optica spectrum disorders

“…Our ndings suggest that the clinical characteristics of patients with VLO-NMOSD may be related to immunosenescence, which may be importance when considering the pathogenesis of autoimmune diseases [1][2][3][4][5][6]33]. Our ndings suggest that the clinical characteristics of patients with VLO-NMOSD may be related to immunosenescence.…”

“…Aging is de ned as "physiologically progressive, generalized degeneration and decay of somatic tissues and immune system (immunosenescence) with increasing probability of death" [1]. Immunosenescence is best known in T-cell subsets in the form of cellular and molecular alterations and thymic atrophy, which result in reduced function of T-and B-cells [2][3][4].…”

Autoantibodies against the prion protein in individuals with PRNP mutations

“…All other analyses were performed post hoc. We used already established predictors of autoimmune disease such as age 26 and sex 27 as well as storage conditions known to affect antibody responses such as presence of coagulation factors 28 as covariates in our multivariate regression model. Using the purposeful selection of covariates method as described previously, 29 effects of covariates on autoantibody titers were…”

“…Presence or absence of a pathogenic PRNP mutation was not associated with significant changes in anti-PrP C autoantibody reactivity (table 3). In addition, we matched 62 cases and controls on age (±5 years), sex, and blood sample type [26][27][28] (table e-2, doi. org/10.5061/dryad.08kprr4xk).…”