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. 2022 Oct 31;146(4):1436–1452. doi: 10.1093/brain/awac404

Figure 3.

Figure 3

B cells, plasma cells, intrathecal immunoglobulin synthesis and complement in GAD-TLE. (A) Intrathecal total immunoglobulin synthesis in individual patients with GAD-TLE over time. Please note that all individuals with serial data available went from ‘intrathecal production’ to ‘no intrathecal production’. (B) Quantification of CD20+ B cells. The graph shows the number of B cells from the various patients during the course of disease. The Spearman correlation test revealed a significant decrease with ongoing disease duration (P = 0.0026, r = −0.7310). (C) Low-magnification image of CD20 staining of the hippocampus of Patient 2. Every black dot indicates a single B cell. (D) Higher magnification of CD20 staining showing few CD20+ B cells in Patient 2 with GAD encephalitis. (E) Quantification of CD138+ plasma cells in the hippocampi of GAD encephalitis patients. The Spearman correlation test revealed a significant decrease with ongoing disease duration (P = 0.0001, r = −0.8365). (F) Presence of CD138+ plasma cells in hippocampus of a GAD-TLE brain (Patient 2). Every dot indicates a single CD138+ plasma cell. (G) Higher magnification of the hippocampus stained for CD138, showing multiple plasma cells in the parenchyma. (H) Multiplex staining for IgG (IgG1, IgG2, IgG3 and IgG4) subsets in Patient 2. Whereas the serum in blood vessels stains positive for IgG2 (red arrowhead), multiple IgG1+ plasma cells (green arrowheads) and a single IgG3+ plasma cell (cyan arrowhead) can be seen in the parenchyma. (I–O) Staining for C3d and C9neo was performed in various controls and GAD-TLE patients. (I) C3d and C9neo are both negative in a normal control. (J) C3d and C9neo staining both can be seen around the blood vessels in the spinal cord of a neuromyelitis optica (NMO) patient. (K) In the cortex of an Alzheimer's disease brain, C3d staining can be seen in amyloid plaques (arrow). These plaques are negative for C9neo. (L) In a TLE patient, C3d upregulation can be seen in neurons of the dentate gyrus. These neurons are negative for C9neo. Magnifications in I–L are identical and indicated by the bar in I. (M–O) C3d and C9neo stainings in three GAD-TLE patients (M, Patient 1; N, Patient 4; and O, Patient 6). In all three patients C3d reactivity (left) can be seen in neurons, partially with shrunken cytoplasm (arrows) indicating neuronal damage. C9neo reactivity (right) in the same areas, however, is negative. Magnifications in M–O are identical and indicated by the bar in M.