Accelerated immune aging was correlated with lupus‐associated brain fog in reproductive‐age systemic lupus erythematosus patients

Abstract

Aims: Cognitive impairment is common in systemic lupus erythematosus (SLE) patients with substantial adverse effects on function and quality of life. One hypothesis to understand the mechanisms of cognitive impairment in SLE is accelerated immunosenescence. The aim of this study is to observe the correlation between immunosenescence with cognitive impairment in patients with SLE. Methods: Sixty-one female SLE patient were measured for CD4 and CD8 T cellassociated senescence markers, including percentage of end-stage differentiated T cells (CD4 and CD8 T cells expressing CD57 + or loss of CD28 expression), of naïve T cells (CD4 + CD45RA + and CD8 + CD45RA + ), memory T cells (CD4 + CD45RO + and CD8 + CD45RO + ), and antigen-experienced T cells (CD4 + KLRG1 + and CD8 + KLRG1 + ) which were measured using flow cytometry. One hallmark of immunosenescence called immune risk profile (IRP) was defined by an inverted ratio of CD4 and CD8. Cognitive functions were measured by Mini-Mental State Examination (MMSE) and Montréal Cognitive Assessment (MOCA) questionnaire. Results: Thirty-six (59.1%) SLE patients who had IRP develop significantly lower attention and recall from both MMSE (P = .005 and P = .000) and MOCA (P = .017 and P = .000) examinations. Decreased visuospatial ability was also found in patients with IRP measured by MOCA (P = .046). There was a negative correlation between memory CD4 + CD45RO + T cells with recall and visuospatial domain (R = −0.204, P = .039 and R = −0.250, P = .033; respectively), and negative correlation between CD8 + CD28 -T cells with recall and attention domain (R = −0.249, P = .027 and R = −0.145, P = .048, respectively). Conclusion: Systemic lupus erythematosus patients develop an accelerated immunosenescence which contributes to cognitive dysfunction, especially in attention, recall, and visuospatial domains. K E Y W O R D S immunosenescence, lupus-associated brain fog, systemic lupus erythematosus | 621 KALIM et AL.

The Cognitive and Psychiatric Subacute Impairment in severe Covid-19.

“…The scores obtained were abnormal for the 34.2% of the sample for the TMTs A. This nding is commonly described in patients with in ammatory-based encephalopathies 29,43 . The two MoCA subdomains included in this component that were less affected: Animal naming and Orientation.…”

“…Cognitive and neuropsychiatric impairment persisting months after acute SARS-CoV-2 infection has been described [25][26][27][28][29] . However, we lack detailed studies that analyze the selective involvement of the different cognitive domains using speci cally designed tests, it impacts on quality of life and the possible existence of related biomarkers.…”

The Role of T Cell Senescence in Neurological Diseases and Its Regulation by Cellular Metabolism

“…Interestingly, reversed CD4:CD8 ratio, increased percentage of effector memory and reduced numbers of naïve CD4 + T cells, all potential signs of T cell senescence, were correlated with the presence of chronic viral infections and cognitive dysfunctions in old individuals (38)(39)(40). Similarly, expansion of CD8 + CD28 -T cells was associated with worse cognitive performances in patients with rheumatoid arthritis (41), and higher numbers of memory CD4 + T cells and CD8 + sTC negatively correlated with cognitive impairment in systemic lupus erythematous patients (42). These works support the idea that persistent T cell activation and maturation observed during chronic viral infections and autoimmune diseases may generate detrimental sTC that cause or sustain cognitive impairment, most likely through pro-inflammatory mechanisms.…”

Self-reported cognitive impairment in individuals with Primary Immunodeficiency Disease

“…There is one report of neurodegenerative changes in the PID population ( Ziegner et al., 2002 ). The issue of memory impairment is recognized in many other autoimmune or inflammatory conditions, including lupus ( Kalim et al., 2020 ), multiple sclerosis ( Macias Islas and Ciampi, 2019 ), chronic fatigue syndrome ( Ocon, 2013 ; Rasouli et al., 2019 ), and has also been linked to chemotherapy treatment for cancer ( El-Agamy et al., 2019 ; Sordillo and Sordillo, 2020 ). The complexity of this change in cognition may be multifactorial.…”