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. 2024 Jun 18;147(1):102. doi: 10.1007/s00401-024-02754-6

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — Validation of ITIH3 as a biomarker for disease activity and treatment response a Raincloud plot comparing ITIH3 protein abundance levels between PASS-positive and PASS-negative anti-AChR-Ab-positive MG patients measured by ELISA. Here, data sets from the exploration and validation cohorts were combined. Likewise, ITIH3 levels are indicated for anti-MuSK-Ab-positive (n = 10) and seronegative (n = 10) MG patients as well as for patients with CMS (n = 14), IIM (n = 12 with IBM and n = 2 with IMNM), and CIDP (n = 19). HCs indicate baseline levels (n = 53). A p value > 0.05 was classified as not significant, p < 0.05 (*) as significant, p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) as highly significant. b + c Linear regression analysis of ITIH3 protein abundance measured by ELISA and by mass spectrometry in each cohort as indicated. d + e Linear regression analysis of ITIH3 protein levels measured by ELISA and individual QMG scores in each cohort as indicated. In the upper left hand of the plot, p-values are indicated next to the R statistic and the linear function equation describing the regression. f Scatter plot displaying the change to serum ITIH3 as measured by ELISA for treatment responders between baseline and follow-up. Each line indicates the change for an individual patient. g Scatter plot displaying the change to serum ITIH3 as measured by ELISA for treatment non-responders between baseline and follow-up. Each line indicates the change for an individual patient. Treatment response was defined as an improvement of ≥ 3 points on the MG-ADL scale. h Bar graph indicating the change to ITIH3 between follow-up and baseline for responders and non-responders. A one sample t test with zero as hypothetical mean was used for statistical analysis of each group. A p value > 0.05 was classified as not significant, p < 0.05 (*) as significant, p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) as highly significant. Anti-AChR-Ab anti-acetylcholine receptor antibody, CIDP chronic inflammatory demyelinating polyradiculoneuropathy, CMS congenital myasthenic syndrome, HC healthy control, IBM inclusion body myositis, IIM idiopathic inflammatory myopathy, IMNM immune-mediated necrotizing myopathy, ITIH3 inter-alpha-trypsin inhibitor heavy chain H3, MG myasthenia gravis, MuSK muscle-specific kinase, PASS patient-acceptable symptom state, seroneg. seronegative, QMG quantitative MG