Hansen Marie Mathilde, El Mahdaoui Sahla, Hansen Malene Bredahl, Hvalkof Victoria Hyslop, Mahler Mie Reith, Husted Signe Refstrup, Søndergaard Helle Bach, Jennum Poul, Christensen Jeppe Romme, von Essen Marina Rode, Sellebjerg Finn
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
J Neuroimmunol. 2025 Dec 15;409:578751. doi: 10.1016/j.jneuroim.2025.578751. Epub 2025 Sep 8.
Mononuclear phagocytes, including monocytes, macrophages, and microglia, play key roles in the immunopathogenesis of multiple sclerosis (MS). While anti-CD20 monoclonal antibody therapies effectively treat relapsing-remitting MS (RRMS), their secondary effects on mononuclear phagocytes remain unclear.
We analyzed blood and cerebrospinal fluid (CSF) mononuclear phagocytes in patients with RRMS treated with anti-CD20 therapy for 6 months, untreated patients, and controls. Flow cytometry was used to assess the prevalence, phenotype, and cytokine production by blood monocytes. Chitinase-1 (CHIT1) levels in CSF were measured using an enzyme-linked immunosorbent assay.
Blood monocyte frequencies were elevated in untreated and anti-CD20-treated RRMS patients compared with controls. CSF mononuclear phagocytes differed from blood monocytes and were classified as either CD16 or CD16, with CD16 mononuclear phagocytes being enriched in all groups. However, the frequencies of CD16 mononuclear phagocytes in CSF were higher in untreated and anti-CD20-treated RRMS patients compared to controls, and the expression of CD206 and CCR2 on CD16 mononuclear phagocytes differed between untreated patients and controls. Blood monocyte cytokine production did not differ between untreated and anti-CD20-treated patients. CSF CHIT1 levels were elevated in both untreated and anti-CD20-treated patients.
The comparable blood and CSF mononuclear phagocyte phenotypes, along with persistently elevated CHIT1 concentrations in CSF of untreated and anti-CD20-treated patients with RRMS, suggest that residual innate immune activation is not normalized by 6 months of anti-CD20 treatment.
单核吞噬细胞，包括单核细胞、巨噬细胞和小胶质细胞，在多发性硬化症（MS）的免疫发病机制中起关键作用。虽然抗CD20单克隆抗体疗法可有效治疗复发缓解型MS（RRMS），但其对单核吞噬细胞的次要影响仍不清楚。
我们分析了接受抗CD20治疗6个月的RRMS患者、未治疗患者和对照组的血液和脑脊液（CSF）单核吞噬细胞。采用流式细胞术评估血液单核细胞的患病率、表型和细胞因子产生情况。使用酶联免疫吸附测定法测量CSF中的几丁质酶-1（CHIT1）水平。
与对照组相比，未治疗和抗CD20治疗的RRMS患者的血液单核细胞频率升高。CSF单核吞噬细胞与血液单核细胞不同，分为CD16⁺或CD16⁻，所有组中CD16⁺单核吞噬细胞均富集。然而，与对照组相比，未治疗和抗CD20治疗的RRMS患者CSF中CD16⁺单核吞噬细胞的频率更高，未治疗患者和对照组之间CD16⁺单核吞噬细胞上CD206和CCR2的表达不同。未治疗和抗CD20治疗的患者之间血液单核细胞细胞因子产生没有差异。未治疗和抗CD20治疗的患者CSF中CHIT1水平均升高。
未治疗和接受抗CD20治疗的RRMS患者血液和CSF单核吞噬细胞表型具有可比性，且CSF中CHIT1浓度持续升高，这表明6个月的抗CD20治疗未能使残留的固有免疫激活恢复正常。
