Evidence for Peripheral Immune Activation in Parkinson’s Disease

Abstract

BackgroundAccumulating evidence has revealed that peripheral immunity is involved in Parkinson’s disease (PD). However, the results regarding the percentage of T-cell subsets are inconsistent, and the changes of immunoglobins levels have been seldom studied in PD patients.MethodsSerum levels of the percentage of T-cell subsets and immunoglobulins were measured in 761 PD patients and 761 age- and gender-matched healthy controls. The correlations between the variables of peripheral immune activation (PIA) and the clinical characteristics of PD were analyzed using correlation analysis.ResultsThe pooled results showed that PD patients had higher proportional levels of CD3+ T and CD4+ T lymphocytes than healthy controls. CD8+ T cell percentages were similar in PD patients and controls, and the CD4/CD8 ratio was significantly higher in the PD population. No significant differences in IgG, IgA, or IgM levels between these two groups were found. CD4+ T cell percentage was inversely correlated with the H&Y stage, and IgG level was positively correlated with disease duration and UPDRS part III. Subgroup analyses showed that these associations existed in female patients, but not in male patients.ConclusionThe enhanced immune activation in the peripheral system is indicated in PD, and dynamic alterations in CD4+ T cell percentage and IgG level suggest an active role for peripheral immunity in the disease progression, especially in female PD patients.

T Lymphocytes in Parkinson’s Disease

“…A meta-analysis including 21 case-control studies and 943 PD patients confirmed that the numbers of CD3 + and CD4 + T cells were significantly decreased in PD [23]. In contrast with these results, another study found that PD patients had an increase in the percentage of CD3 + and CD4 + T s and the CD4 + /CD8 + ratio [24], whereas other groups did not find any significant difference in the percentage of both CD4 + and CD8 + between PD patients and controls [17,18,25]. Undoubtedly, the composition of peripheral T cells from PD patients in the reported studies was quite heterogeneous, which could be explained by the influence of ethnic variations or other relevant disease-related confounders.…”

The role of Th17 cells/IL-17A in AD, PD, ALS and the strategic therapy targeting on IL-17A

“…In 2021, we compared 761 age–gender matched healthy controls with 761 PD patients and found that the ratio of CD4/CD8 in PD patients was higher than that in healthy controls, and the percentage of CD4+ T cells was negatively correlated with the Hoehn and Yahr (H&Y) stage [ 145 ]. However, we did not compare the subtypes of CD4+ T cells.…”

Identification and validation of key molecules associated with humoral immune modulation in Parkinson’s disease based on bioinformatics

“…In addition, during the inflammatory progress of CNS, peripheral myeloid cells (such as monocytes) can be recruited into the brain through disturbed BBB and further participate in the inflammatory processes ( 27 ). Peripheral immune activation is enhanced in PD patients, and dynamic changes in the percentage of CD4+ T cells and IgG level suggest that peripheral immunity plays a positive role in initiation or exacerbation of neurodegeneration ( 30 ). The autoantibodies against α-synuclein were related to disease status in the serum and cerebrospinal fluid of PD patients ( 31 ); furthermore, a study confirmed that the repertoire of high-affinity anti-α-synuclein autoantibodies was significantly reduced in prodromal phases of PD ( 32 ), which indicates that impaired reactivity towards α-synuclein occurs prior to disease onset and humoral immune response is involved in the pathophysiology of neurodegeneration.…”