Cytokine profiling in patients with hepatic glycogen storage disease: Are there clues for unsolved aspects?. (February 2023)

• Record Type: Journal Article
• Authors: Colonetti, Karina; Pinto e Vairo, Filippo; Siebert, Marina; Nalin, Tatiéle; Poloni, Soraia; Fernando Wurdig Roesch, Luiz; Fischinger Moura de Souza, Carolina; Cabral Pinheiro, Franciele; Vanessa Doederlein Schwartz, Ida
• Is Part Of: Cytokine. Volume 162(2023)
• Publication Date: 2023-02
• Subjects: Cytokines -- Glycogen storage disease -- Chemokines; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2022.156088
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Exploratory study in patients with Hepatic GSD and age-sex-matched healthy controls. Multiplex assay determined the plasma levels of 20 cytokines. Cytokines data were combined with clinical and biochemical aspects of GSD patients. Imbalance in the inflammatory cascade correlated with triglyceride levels. New immune insights on HCA, Anemia and GSF-treatment mechanisms were discussed. Abstract: Introduction: Hepatic Glycogen Storage Diseases (GSD) are rare genetic disorders in which the gluconeogenesis pathway is impaired. Cytokines control virtually every aspect of physiology and may help to elucidate some unsolved questions about phenotypes presented by GSD patients. Methods: This was an exploratory study in which 27 GSD patients on treatment (Ia = 16, Ib = 06, III = 02, IXα = 03) and 24 healthy age- and sex-matched subjects had plasma samples tested for a panel of 20 cytokines (G-CSF, GM-CSF, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17A, GRO, IP-10/CXCL10, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, MDC/CCL22, IFN-γ, TNF-α, TNF-β, VEGF) through a multiplex kit and analyzed in comparison to controls and among patients, regarding to clinical features as anemia, hepatic adenocarcinoma and triglyceride levels. Results: Patients (GSD-Ia/III/IX) presented reduced levels of IL-4 (p = 0.040), MIP-1α/CCL3 (p = 0.003), MDC/CCL22 (p < 0.001), TNF-β (p = 0.045) and VEGF (p = 0.043) compared to controls. When different types of GSD were compared, G-CSF was higher in GSD-Ib than -Ia (p < 0.001) and than -III/IX (p = 0.033) patients; IL-10 was higher in GSD-Ib than in GSD-Ia patients (p = 0.019); and GSD-III/IX patients had increased levels of IP-10/CXCL10 than GSD-Ib patients (p = 0.019). When GSD-I patients were gathered into the same group and compared with GSD-III/IX patients, IP10/CXCL10 and MCP-1 were higher in the latter group (p = 0.005 and p = 0.013, respectively). GSD-I patients with anemia presented higher levels of IL-4 and MIP-1α in comparison with patients who had not. Triglyceride level was correlated with neutrophil count and MDC levels on GSD-Ia patients without HCA. Conclusion: Altogether, altered levels of cytokines in GSD-I patients reflect an imbalance in immunoregulation process. This study also indicates that neutrophils and some cytokines are affected by triglyceride levels, and future studies on the theme should consider this variable.