PMC10322512_01
Fluid-attenuated inversion recovery (FLAIR) (A-L) and T1-weighted (M-X) brain MRI obtained 3 months before admission (A-D, M-P), on admission (E-H, Q-T), and 9 weeks after the initial treatment (I-L, U-X). Diffuse cerebral atrophy was observed on admission (E-H, Q-T), but rapidly recovered after immunotherapy (I-L, U-X).
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Brain magnetic resonance imaging (MRI) did not show clear abnormal intensities or specific atrophy (Figures 1A-D, M-P). Serum paraneoplastic screening by fixed TBA did not show any significances (Supplementary Figure 1); however, EUROLINE PNS 12 Ag (Euroimmun) showed a weak positive 6 and 10, suggesting a low titer of anti-AMPH antibodies. Brain MRI revealed semi-rapidly progressive DCA over a period of 3 months without clear abnormal intensities (Figures 1E-H, Q-T). Over the next 5 weeks (9 weeks after initial treatment), her cognitive impairment had almost fully resolved (HDS-R score of 28) and DCA had partially recovered (Figures 1I-L, U-X).
Gastroscopy and pathological findings. Two lesions of type 0-IIa gastric tumor (A). Hematoxylin-eosin staining shows two adenocarcinomas (B, C).
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Although colonoscopy and random skin biopsy showed normal findings, gastroscopy revealed type 0-IIa gastric tumors, and histological results suggested gastric adenocarcinomas with no evidence of metastasis (Figure 2A). The pathological diagnosis was two well-differentiated adenocarcinoma lesions (Figures 2B, C). The clinical timeline is shown in Supplementary Figure 2.
Immunoprecipitation assay. Flag-AMPH combined protein was successfully expressed in HEK-293T cells. However, the anti-FLAG antibody did not show any non-specific bands (A). The patient's serum contained anti-AMPH antibodies, which decreased after immunotherapy (B, C). AMPH, amphiphysin; FLAG, anti-DDDDK-tag; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Ig, immunoglobulin. ***p < 0.0001.
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A subsequent western blotting analysis revealed the presence of anti-AMPH antibodies and their continuous decrease 10 months after immunotherapy (Figures 3A-C).