Metabolic alterations of the immune system in the pathogenesis of autoimmune diseases

Blanco, Luz P.; Kaplan, Mariana J.

doi:10.1371/journal.pbio.3002084

Cited by 14 publications

(6 citation statements)

References 60 publications

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“…The metabolism of acylcarnitine and carnitine, changes in fatty acid metabolism, as well as TCA cycle metabolites have been linked to mitochondrial dysfunction [ 26 , 57 , 61 , 91 , 109 , 111 , 113 ]. Reactive oxygen species, antioxidant metabolites, glucogenic amino acid metabolites [ 58 , 114 , 115 ], and the accumulation of signaling metabolites were also reported [ 116 ]. Developing metabolites associated with mitochondrial dysfunction may be a focus for future research.…”

Section: Discussionmentioning

confidence: 99%

Metabolite Alterations in Autoimmune Diseases: A Systematic Review of Metabolomics Studies

Mujalli,

Farrash,

Alghamdi

et al. 2023

Metabolites

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Autoimmune diseases, characterized by the immune system’s loss of self-tolerance, lack definitive diagnostic tests, necessitating the search for reliable biomarkers. This systematic review aims to identify common metabolite changes across multiple autoimmune diseases. Following PRISMA guidelines, we conducted a systematic literature review by searching MEDLINE, ScienceDirect, Google Scholar, PubMed, and Scopus (Elsevier) using keywords “Metabolomics”, “Autoimmune diseases”, and “Metabolic changes”. Articles published in English up to March 2023 were included without a specific start date filter. Among 257 studies searched, 88 full-text articles met the inclusion criteria. The included articles were categorized based on analyzed biological fluids: 33 on serum, 21 on plasma, 15 on feces, 7 on urine, and 12 on other biological fluids. Each study presented different metabolites with indications of up-regulation or down-regulation when available. The current study’s findings suggest that amino acid metabolism may serve as a diagnostic biomarker for autoimmune diseases, particularly in systemic lupus erythematosus (SLE), multiple sclerosis (MS), and Crohn’s disease (CD). While other metabolic alterations were reported, it implies that autoimmune disorders trigger multi-metabolite changes rather than singular alterations. These shifts could be consequential outcomes of autoimmune disorders, representing a more complex interplay. Further studies are needed to validate the metabolomics findings associated with autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Metabolite Alterations in Autoimmune Diseases: A Systematic Review of Metabolomics Studies

Mujalli,

Farrash,

Alghamdi

et al. 2023

Metabolites

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“…In addition, the altered state of the cells provokes mitochondria to work at a higher energy level to maintain the proliferative effect. This leads to metabolic and immune dysfunction related to autoimmunity [28].…”

Section: Discussionmentioning

confidence: 99%

JAK inhibitors improve ATP production and mitochondrial function in rheumatoid arthritis: a pilot study

Mihaylova,

Kazakova,

Batalov

et al. 2023

Rheumatol Int

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Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated by inflammation of the synovial tissue and autoantibody production. Oxidative stress and free radicals are known to be indirectly implicated in joint damage and cartilage destruction in RA. Several studies describe the presence of mitochondrial dysfunction in RA, but few of them follow the dynamics in energy parameters after therapy. The aim of our investigation is to evaluate the direct effect of JAK inhibitors on cellular metabolism (and under induced oxidative stress) in RA patients. Ten newly diagnosed RA patients were included in the study. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated before and 6 months after therapy with JAK inhibitors. A real-time metabolic analysis was performed to assess mitochondrial function and cell metabolism in PBMCs. Sonographic examination, DAS28 and conventional clinical laboratory parameters were determined also prior and post therapy. A significant decrease in proton leak after therapy with JAK inhibitors was found. The increased production of ATP indicates improvement of cellular bioenergetics status. These findings could be related to the catalytic action of JAK inhibitors on oxidative phosphorylation which corresponds to the amelioration of clinical and ultra-sonographic parameters after treatment. Our study is the first to establish the dynamics of mitochondrial parameters in PBMCs from RA patients before and after in vivo therapy with JAK inhibitors.

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“…Therefore, damaged mitochondria should be cleared from cells. If the clearance process is disrupted, the mitochondrial DNA (mtDNA) in the cytoplasm can activate nuclear sensing pathways, including cyclic guanosine monophosphate‐adenosine monophosphate (GMP–AMP) synthase (cGAS) and Stimulator of Interferon Genes (STING) pathways (cGAS‐STING), promoting type I IFN synthesis 30 . Altogether, this oxidative and inflammatory process enhances B‐cell differentiation into plasmablasts, with an undesired production of auto‐antibodies characteristic of SLE 30 .…”

Section: B‐cell Metabolism In Health and Diseasementioning

confidence: 99%

“…If the clearance process is disrupted, the mitochondrial DNA (mtDNA) in the cytoplasm can activate nuclear sensing pathways, including cyclic guanosine monophosphate‐adenosine monophosphate (GMP–AMP) synthase (cGAS) and Stimulator of Interferon Genes (STING) pathways (cGAS‐STING), promoting type I IFN synthesis 30 . Altogether, this oxidative and inflammatory process enhances B‐cell differentiation into plasmablasts, with an undesired production of auto‐antibodies characteristic of SLE 30 . Thus, strategies to promote mitochondrial functionality and reduce oxidative stress may contribute to immune tolerance and, therefore, may contribute to the effectiveness of treatments for autoimmune disorders such as SLE.…”

Section: B‐cell Metabolism In Health and Diseasementioning

confidence: 99%

“… 30 Altogether, this oxidative and inflammatory process enhances B‐cell differentiation into plasmablasts, with an undesired production of auto‐antibodies characteristic of SLE. 30 Thus, strategies to promote mitochondrial functionality and reduce oxidative stress may contribute to immune tolerance and, therefore, may contribute to the effectiveness of treatments for autoimmune disorders such as SLE.…”

Section: B‐cell Metabolism In Health and Diseasementioning

confidence: 99%

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Metabolic imbalance driving immune cell phenotype switching in autoimmune disorders: Tipping the balance of T‐ and B‐cell interactions

Barberis,

Rojas López

2024

Clinical & Translational Med

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The interplay between the immune system and the metabolic state of a cell is intricate. In all phases of an immune response, the corresponding metabolic changes shall occur to support its modulation, in addition to the signalling through the cytokine environment and immune receptor stimulation. While autoimmune disorders may develop because of a metabolic imbalance that modulates switching between T‐cell phenotypes, the effects that the interaction between T and B cells have on one another's cellular metabolism are yet to be understood in disease context. Here, we propose a perspective which highlights the potential of targeting metabolism to modulate T‐ and B‐cell subtypes populations as well as T–B and B–T cell interactions to successfully treat autoimmune disorders. Specifically, we envision how metabolic changes can tip the balance of immune cells interactions, through definite mechanisms in both health and disease, to explain phenotype switches of B and T cells. Within this scenario, we highlight targeting metabolism that link inflammation, immunometabolism, epigenetics and ageing, is critical to understand inflammatory disorders. The combination of treatments targeting immune cells that cause (T/B) cell phenotype imbalances, and the metabolic pathways involved, may increase the effectiveness of treatment of autoimmune disorders, and/or ameliorate their symptoms to improve patients’ quality of life.

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Metabolic alterations of the immune system in the pathogenesis of autoimmune diseases

Cited by 14 publications

References 60 publications

Metabolite Alterations in Autoimmune Diseases: A Systematic Review of Metabolomics Studies

Metabolite Alterations in Autoimmune Diseases: A Systematic Review of Metabolomics Studies

JAK inhibitors improve ATP production and mitochondrial function in rheumatoid arthritis: a pilot study

Metabolic imbalance driving immune cell phenotype switching in autoimmune disorders: Tipping the balance of T‐ and B‐cell interactions

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