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Sex-driven variability in TSPO-expressing microglia in MS patients and healthy individuals
Sini Laaksonen1,2,3, Maija Saraste1,3, Marjo Nylund1,2,3,4
1Turku PET Centre, Turku University Hospital, University of Turku, Turku, Finland.
Background:
Males with multiple sclerosis (MS) have a higher risk for disability progression than females, but the reasons for this are unclear.
Objective:
We hypothesized that potential differences in TSPO-expressing microglia between female and male MS patients could contribute to sex differences in clinical disease progression.
Methods:
The study cohort consisted of 102 MS patients (mean (SD) age 45.3 (9.7) years, median (IQR) disease duration 12.1 (7.0-17.2) years, 72% females, 74% relapsing-remitting MS) and 76 age- and sex-matched healthy controls. TSPO-expressing microglia were measured using the TSPO-binding radioligand [11C](R)-PK11195 and brain positron emission tomography (PET). TSPO-binding was quantified as distribution volume ratio (DVR) in normal-appearing white matter (NAWM), thalamus, whole brain and cortical gray matter (cGM).
Results:
Male MS patients had higher DVRs compared to female patients in the whole brain [1.22 (0.04) vs. 1.20 (0.02), p = 0.002], NAWM [1.24 (0.06) vs. 1.21 (0.05), p = 0.006], thalamus [1.37 (0.08) vs. 1.32 (0.02), p = 0.008] and cGM [1.25 (0.04) vs. 1.23 (0.04), p = 0.028]. Similarly, healthy men had higher DVRs compared to healthy women except for cGM. Of the studied subgroups, secondary progressive male MS patients had the highest DVRs in all regions, while female controls had the lowest DVRs.
Conclusion:
We observed higher TSPO-binding in males compared to females among people with MS and in healthy individuals. This sex-driven inherent variability in TSPO-expressing microglia may predispose male MS patients to greater likelihood of disease progression.
Insights
Males with multiple sclerosis (MS) show higher brain TSPO-binding, indicating more microglia activation. This may explain why men with MS experience greater disability progression than women.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Multiple Sclerosis Pathophysiology
Background:
- Males with multiple sclerosis (MS) exhibit a higher risk of disability progression compared to females.
- The underlying reasons for this observed sex disparity in MS clinical outcomes remain unclear.
Purpose of the Study:
- To investigate potential sex differences in microglia activation in MS.
- To test the hypothesis that differences in TSPO-expressing microglia contribute to sex-based disparities in MS disease progression.
Main Methods:
- Utilized brain positron emission tomography (PET) with the TSPO-binding radioligand [11C](R)-PK11195.
- Quantified TSPO-binding as distribution volume ratio (DVR) in normal-appearing white matter (NAWM), thalamus, whole brain, and cortical gray matter (cGM).
- The study included 102 MS patients and 76 healthy controls, matched for age and sex.
Main Results:
- Male MS patients demonstrated significantly higher TSPO-binding (DVR) across all measured brain regions compared to female MS patients.
- Healthy males also exhibited higher TSPO-binding than healthy females, except in cortical gray matter.
- Secondary progressive male MS patients displayed the highest TSPO-binding, while female controls showed the lowest.
Conclusions:
- Observed higher TSPO-binding in males compared to females in both MS patients and healthy individuals.
- This sex-driven variability in microglia activation (TSPO-expressing microglia) may contribute to the increased susceptibility of male MS patients to greater disease progression.
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