Laaksonen Sini, Saraste Maija, Nylund Marjo, Hinz Rainer, Snellman Anniina, Rinne Juha, Matilainen Markus, Airas Laura
Turku PET Centre, Turku University Hospital, University of Turku, Turku, Finland.
Neurocenter, Turku University Hospital, Turku, Finland.
Front Neurol. 2024 Feb 20;15:1352116. doi: 10.3389/fneur.2024.1352116. eCollection 2024.
Males with multiple sclerosis (MS) have a higher risk for disability progression than females, but the reasons for this are unclear.
We hypothesized that potential differences in TSPO-expressing microglia between female and male MS patients could contribute to sex differences in clinical disease progression.
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 C-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).
Male MS patients had higher DVRs compared to female patients in the whole brain [1.22 (0.04) vs. 1.20 (0.02), = 0.002], NAWM [1.24 (0.06) vs. 1.21 (0.05), = 0.006], thalamus [1.37 (0.08) vs. 1.32 (0.02), = 0.008] and cGM [1.25 (0.04) vs. 1.23 (0.04), = 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.
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.
患有多发性硬化症（MS）的男性比女性有更高的残疾进展风险，但原因尚不清楚。
我们假设女性和男性MS患者中表达TSPO的小胶质细胞的潜在差异可能导致临床疾病进展的性别差异。
研究队列包括102例MS患者（平均（标准差）年龄45.3（9.7）岁，中位（四分位间距）病程12.1（7.0 - 17.2）年，72%为女性，74%为复发缓解型MS）和76名年龄及性别匹配的健康对照。使用TSPO结合放射性配体C-PK11195和脑正电子发射断层扫描（PET）测量表达TSPO的小胶质细胞。TSPO结合以分布容积比（DVR）在正常外观白质（NAWM）、丘脑、全脑和皮质灰质（cGM）中进行定量。
与女性患者相比，男性MS患者在全脑[1.22（0.04）对1.20（0.02），P = 0.002]、NAWM[1.24（0.06）对1.21（0.05），P = 0.006]、丘脑[1.37（0.08）对1.32（0.02），P = 0.008]和cGM[1.25（0.04）对1.23（0.04），P = 0.028]中有更高的DVR。同样，除cGM外，健康男性比健康女性有更高的DVR。在研究的亚组中，继发进展型男性MS患者在所有区域的DVR最高，而女性对照的DVR最低。
我们观察到在MS患者和健康个体中，男性比女性有更高的TSPO结合。这种由性别驱动的表达TSPO小胶质细胞的内在变异性可能使男性MS患者更易出现疾病进展。
