Systemic monocyte activation patterns in early Parkinson’s disease appear to differ by gender

Study data published in NPJ Parkinson’s Disease identified gender differences in peripheral blood monocyte activation in patients with early-stage Parkinson’s disease (PD).

In a gene expression study on people with and without Parkinson’s, both patient status and gender had a clear influence on monocyte activation. These results underscore the importance of monocyte activation in Parkinson’s disease and outline the different effects of gender on the pathophysiology of the disease.

Recent research suggests that the immune system plays a crucial role in the pathogenesis of Parkinson’s disease. In particular, gene expression studies have shown prominent expression of PD-associated genes in the blood monocytes of affected patients.

Continue reading

To better understand the relationship between peripheral blood monocyte activation and PD, the researchers recruited a patient population with untreated early PD, defined as within 2 years of onset of symptoms. The patients were matched with healthy control group participants according to their age.

Blood monocytes were isolated using a negative selection approach; conventional flow cytometry was used to define monocyte populations. RNA sequencing and gene set enrichment analyzes were also performed to determine gene expression patterns in isolated monocytes. A computational model that included patient or control group status, gender and the interaction between patient or control group status and gender was used to identify different gene expression patterns of patients and control group participants.

A total of 18 patients with PD and 16 participants in the control group were included, of which 11 (61.1%) and 10 (62.5%) were men, respectively. No significant demographic differences were observed between the patients and the participants in the control group. The mean age was comparable between patients and participants in the control group (P = .21) and between men and women (P = .77).

According to flow cytometry analyzes, there was moderate evidence of a decrease in the population of classical monocytes, intermediate monocytes and non-classical monocytes in patients with PD compared to the participants in the control group.

Computer models found a significant influence of gender on the differential monocyte expression between patients and participants in the control group. In the women, a total of 347 genes were expressed differently between the patient and control groups. In men, however, only 15 differently expressed genes were identified between the groups.

Men and women shared only one common differently expressed gene: CEBPG, a transcription factor. In men, this gene was increased in healthy control group participants compared to patients; in women, the gene was more strongly expressed in patients than in participants in the control group. The lack of overlap in gene expression suggests that the pathogenic process of Parkinson’s disease differs widely by gender.

The pathway analysis showed a “consistent signature of changes in inflammation signaling” in women with Parkinson’s disease compared to healthy women. In men, however, the pattern associated with PD was much more heterogeneous: “The KEGG-cytokine-cytokine-receiving interaction pathway was changed, [as] with females, but other pathways were changed … were more diverse. ”Thus, in early Parkinson’s disease, gender seems to significantly influence the expression of disease-associated genes in peripheral monocytes.

As limitations to the study, the researchers cited the small study cohort and the use of a pooled monocyte analysis technique instead of a single cell sequencing approach. Nevertheless, these data underscore the importance of systemic monocyte activation in Parkinson’s disease and the different effects of gender on disease pathology.

“Identifying an inflammatory signature in the blood of Parkinson’s patients opens the door to new approaches for both biomarkers and treatment,” the study researchers wrote. “As a biomarker, the assessment of monocyte activation has the potential to be a measure of disease activation and possibly the targeted effectiveness of an immunomodulatory treatment.”

reference

Carlisle SM, Qin H, Hendrickson RC, et al. Gender differences in peripheral blood monocyte activation in early Parkinson’s disease. NPJ Parkinsons Dis. Published online April 13, 2021. doi: 10.1038 / s41531-021-00180-z

This article originally appeared on Psychiatry Advisor