ArticleFrontiers in immunology2026
Enzyme replacement therapy (ERT) combined with transient low-dose methotrexate (TLD-MTX) results in age- and disease-dependent immune profile changes in Infantile- vs. late-onset Pompe disease patients.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Transient low-dose methotrexate (MTX) induces long-term immune tolerance to enzyme replacement therapy (ERT) in Pompe disease; however, the underlying immunological mechanisms remain unclear. We hypothesized that TLD-MTX would reduce immune activation and induce a regulatory phenotype in patients with Infantile-Onset Pompe Disease (IOPD) and Late-Onset Pompe Disease (LOPD) treated with ERT. Methods: We evaluated immune cell profile changes in patients treated with ERT+MTX using multiparameter flow cytometry on peripheral blood mononuclear cells collected at baseline and six months post-treatment. We analyzed 40 immune parameters in (1) thirteen unpaired samples from ERT+MTX-untreated (n=10) and -treated (n=3) IOPD patients and (2) six paired pre- and post-treatment samples from LOPD (n=6) patients. Linear regression analyses were used to assess correlations between immune parameters and disease activity measured by urinary glucose tetrasaccharide (Glc Results: In IOPD, ERT+MTX-treated samples (median age: 12.3 months) showed reduced % CD16 Discussion: These findings demonstrate distinct immune profiles before and after ERT+MTX treatment in IOPD and LOPD patients. In IOPD, reduced pro-inflammatory monocytes and memory T cells provide evidence to suggest decreased immune activation. In LOPD, increased TIGIT
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