Inflammation in the deep grey matter (DGM) lesions of patients with multiple sclerosis (MS) and controls
| DGM controls | MS NADGM | MS inactive DGM lesions | MS active DGM lesions | ||
|---|---|---|---|---|---|
| CD3-positive T cells/mm2 | Median | 0 | 1.7* | 2.6* | 35.7*† |
| Min.−Max. | 0–5.2 | 0–6.5 | 0–65.9 | 5.5–75.2 | |
| CD68-reactive macrophages/mm2 | Median | 88.5 | 104.3 | 97.5 | 444.8*† |
| Min.−Max. | 68.9–171.9 | 54.4–237.8 | 49.5–445.3 | 334–955.4 | |
| IBA-1-reactive macrophages/mm2 | Median | 55 | 64 | 80.1 | 539.3*† |
| Min.−Max. | 23.7–132.5 | 12.2–251.7 | 26–636.3 | 411.3–1667.2 | |
| iNOS-reactive macrophages/mm2 | Median | 34.4 | 49.5* | 54.7 | 172.5*† |
| Min.−Max. | 2.6–85.1 | 13–131.4 | 18.2–111.5 | 127.3–283.1 | |
| p22-Reactive macrophages/mm2 | Median | 65.8 | 88.5 | 100.7 | 588.6*† |
| Min.–Max. | 23.4–184.6 | 40.8–391.8 | 20–312.5 | 447–1572.3 | |
| CD68-reactive microglia/mm2 | Median | 71.3 | 45.6 | 53.2 | 81 |
| Min.–Max. | 27.2–352.4 | 5.2–186.3 | 15.9–138 | 17.4–166.4 | |
| IBA-1-reactive microglia/mm2 | Median | 157.6 | 151 | 110.7 | 398.3† |
| Min.−Max. | 6.9–874.1 | 8.7–458.3 | 13.9–489.1 | 216.3–730.6 | |
| iNOS-reactive microglia/mm2 | Median | 16.5 | 18.5 | 24.2 | 49.6 |
| Min.−Max. | 5.2–55.6 | 3.5–52.1 | 6.9–164.9 | 13.9–80.1 | |
| p22-Reactive microglia/mm2 | Median | 229.3 | 250.6 | 269.1 | 458.6 |
| Min.−Max. | 20.8–849 | 45.1–590.9 | 39.9–598.1 | 311.2–607.6 | |
| p22-Positive area in % | Median | 0.7 | 1.2 | 1.3 | 5.5*† |
| Min.−Max. | 0.1–3.6 | 0–7.3 | 0.1–7.2 | 1.5–8.5 |
This table depicts an overview of the extent of inflammatory infiltrates in the DGM of patients with MS who were separated according to the presence of active lesions (n=4), inactive lesions (n=15), NADGM (n=30) and control DGM (n=12). Differentiation between microglia and macrophages was based on morphological appearance. The values represent the median values and range.
*Significant p values after correction for multiple testing in comparison with controls.
†Significant p values after correction for multiple testing in comparison with NADGM.
Inflammatory infiltrates of CD3-reactive T cells (p=0.018) and iNOS-positive cells that were differentiated to macrophage morphology (p=0.038) were increased in the non-lesioned DGM of patients with MS compared with control patients. Inactive (p=0.016) and active (p=0.004) lesions showed higher T cell counts than controls. Compared with controls, active DGM lesions displayed increased levels of macrophage morphology in differentiated cells that were CD68- (p=0.004), IBA-1- (p=0.004), iNOS- (p=0.004) and p22-reactive (p=0.004). In addition, the relative area of immunoreactivity for p22 (p=0.020) was increased in the active lesions. Inactive DGM lesions did not differ significantly from the NADGM of patients with MS. In contrast, compared with the NADGM, active DGM lesions showed higher T cell counts (p<0.001) and higher CD68- (p<0.001), IBA-1- (p<0.001), iNOS- (p<0.001) and p22-reactive (p<0.001) macrophages. Active lesions also displayed a higher percentage of p22-positive areas (p=0.040) and more IBA-1-reactive microglia (p=0.050) compared with the NADGM.
IBA-1, ionised calcium-binding adapter molecule 1; iNOS, inducible nitric oxide synthase; NADGM, normal-appearing deep grey matter.