Increased Plasma Levels of Triglyceride-Enriched Lipoproteins Associate with Systemic Inflammation, Lipopolysaccharides, and Gut Dysbiosis in Common Variable Immunodeficiency

Macpherson, Magnhild Eide; Skarpengland, Tonje; Hov, Johannes R.; Ranheim, Trine; Vestad, Beate; Dahl, Tuva B.; Fraz, Mai Sasaki Aanensen; Michelsen, Annika; Holven, Kirsten B.; Fevang, Børre; Berge, Rolf K.; Aukrust, Pål; Halvorsen, Bente; Jørgensen, Silje Fjellgård

doi:10.1007/s10875-023-01475-x

Cited by 5 publications

(17 citation statements)

References 43 publications

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“…However, numerous other patients with no genetic basis yet discovered, have similar medical histories. It is possible that aside from genetics, these different clinical manifestations result from metabolic, environmental factors or epigenetic causes ( Del Pino-Molina et al, 2019 ; Jorgensen et al, 2019 ; Macpherson et al, 2019 ; Ho et al, 2021 ; Rodriguez-Ubreva et al, 2022 ; Macpherson et al, 2023 ). While the majority of patients who carry the “CVID” diagnosis do not yet have a clarified molecular cause, the genetic discoveries in antibody defects continue to reveal the complex immunologic pathways needed to initiate and sustain normal B cell development and the long-term maintenance of B cell memory.…”

Section: Discussionmentioning

confidence: 99%

Genetics and clinical phenotypes in common variable immunodeficiency

Cunningham-Rundles,

Casanova,

Boisson

2024

Front. Genet.

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Common variable immunodeficiency (CVID) is one of the most common symptomatic groups of inborn errors of immunity. In addition to infections resulting from insufficient levels of immune globulins and antibodies, many patients develop inflammatory or autoimmune conditions, which are associated with increased mortality. This aspect of CVID has been the focus of many studies, and dissecting the clinical phenotypes of CVID, has had the goal of providing biomarkers to identify these subjects, potentially at the time of diagnosis. With the application of whole exome (WES) and whole genome analyses, an increasing number of monogenic causes of CVID have been elucidated. From the standpoint of the practicing physician, an important question is whether the clinical phenotype, particularly the occurrence of autoinflammation of autoimmunity, might suggest the likelihood of identifying a causative mutation, and if possible the gene most likely to underlie CVID. We addressed this question in a patient group of 405 subjects diagnosed with CVID from one medical center.

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Section: Discussionmentioning

confidence: 99%

Genetics and clinical phenotypes in common variable immunodeficiency

Cunningham-Rundles,

Casanova,

Boisson

2024

Front. Genet.

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“…The mechanisms of improving spontaneous abortion and premature rupture of membranes after taking LT4 in gravid females with high-normal TSH levels and TPOAb positivity in the first half of pregnancy include the following: (1) LT4 supplementation can reduce TG, decreasing the production of fatty acids by TG degradation. This, in turn, mitigates the disruption of T-cell subset balance by fatty acids [ 33 ], reducing systemic inflammation [ 34 ]. Additionally, LT4 supplementation may restore intestinal microbiota homeostasis, reducing inflammation caused by intestinal permeability and thereby restoring immune accommodation at the interface between mother and fetus, ultimately lowering the risk of miscarriage [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy

Tian,

Xu,

Ban

et al. 2024

Lipids Health Dis

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Background The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. Methods Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. Results After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). Conclusions For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50 µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117 IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

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“…Recent research studies have reported that TAG metabolism is closely associated with inflammation ( Castoldi et al, 2020 ; Puig et al, 2020 ; Macpherson et al, 2023 ). Though inflammation is beneficial for the regeneration of impaired liver tissue, persistent chronic inflammation can cause a permanent healing state, subsequently initiating liver fibrosis ( de Souza Basso et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Schizandrin C regulates lipid metabolism and inflammation in liver fibrosis by NF-κB and p38/ERK MAPK signaling pathways

et al. 2023

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Liver fibrosis is considered a sustained wound healing response and metabolic syndrome, and its therapy is of great significance for chronic liver disease. Schizandrin C, as one lignan from hepatic protectant Schisandra chinensis, can depress the oxidative effect and lipid peroxidation, and protect against liver injury. In this study, C57BL/6J mice were used to estimate a liver fibrosis model by CCl4, and Schizandrin C exerted an anti-hepatic fibrosis effect, as evidenced by decreased alanine aminotransferase, aspartate aminotransferase and total bilirubin activities in serum, lower hydroxyproline content, recuperative structure and less collagen accumulation in the liver. In addition, Schizandrin C reduced the expressions of alpha-smooth muscle actin and type Ι collagen in the liver. In vitro experiments also revealed that Schizandrin C attenuated hepatic stellate cell activation in both LX-2 and HSC-T6 cells. Furthermore, lipidomics and quantitative real-time PCR analysis revealed that Schizandrin C regulated the lipid profile and related metabolic enzymes in the liver. In addition, the mRNA levels of inflammation factors were downregulated by Schizandrin C treatment, accompanied by lower protein levels of IκB-Kinase-β, nuclear factor kappa-B p65, and phospho-nuclear factor kappa-B p65. Finally, Schizandrin C inhibited the phosphorylation of p38 MAP kinase and extracellular signal-regulated protein kinase, which were activated in the CCl4 fibrotic liver. Taken together, Schizandrin C can regulate lipid metabolism and inflammation to ameliorate liver fibrosis by nuclear factor kappa-B and p38/ERK MAPK signaling pathways. These findings supported Schizandrin C as a potential drug for liver fibrosis.

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Increased Plasma Levels of Triglyceride-Enriched Lipoproteins Associate with Systemic Inflammation, Lipopolysaccharides, and Gut Dysbiosis in Common Variable Immunodeficiency

Cited by 5 publications

References 43 publications

Genetics and clinical phenotypes in common variable immunodeficiency

Genetics and clinical phenotypes in common variable immunodeficiency

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy

Schizandrin C regulates lipid metabolism and inflammation in liver fibrosis by NF-κB and p38/ERK MAPK signaling pathways

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