Increased Serum Interleukin-6 and Tumor Necrosis Factor Alpha Levels in Fabry Disease: Correlation with Disease Burden

Neto, Nilton Salles Rosa; Bento, Judith Campos de Barros; Caparbo, Valéria F.; Pereira, Rosa Maria Rodrigues

doi:10.6061/clinics/2021/e2643

Cited by 8 publications

(12 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neto et al [ 28 ] also described an increased concentration of TNF-α in a female FD cohort of patients treated with ERT, who likewise presented elevated serum levels of IL-6. In this study, the serum IL-6 and TNF-α levels were correlated with the MSSI scores, reflecting greater disease burden in patients with high cytokine levels.…”

Section: Discussionmentioning

confidence: 95%

Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression

Alonso-Núñez,

Pérez-Márquez,

Alves-Villar

et al. 2024

IJMS

View full text Add to dashboard Cite

Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1β, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients’ plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.

show abstract

Section: Discussionmentioning

confidence: 95%

Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression

Alonso-Núñez,

Pérez-Márquez,

Alves-Villar

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…In fact, in studies showing proteomic data from plasma of FD patients, IL-6 was not over-represented in the samples as compared to controls [ 29 , 30 ]. As regards other studies [ 10 , 11 , 12 ], they mainly considered the effects of ERT on IL-6 and looked for differences in the ERT-treated and not-treated subjects, without considering if IL-6 levels were above their normality cut-off.…”

Section: Discussionmentioning

confidence: 99%

“…Besides the toxic role of Gb3 and related glycosphingolipids accumulation in cellular damage, inflammatory and oxidative molecules [ 3 , 4 , 5 , 6 ] have been pointed out as key secondary mediators in the mechanisms leading to irreversible damage in multiple organ systems in FD [ 7 ]. High levels of proinflammatory molecules such as TNF alpha and IL-6 have been reported in FD patients [ 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Increased Soluble Interleukin 6 Receptors in Fabry Disease

Lenzini,

Iori,

Vettore

et al. 2023

JCM

View full text Add to dashboard Cite

Fabry disease (FD) is an X-linked lysosome storage disease that results in the accumulation of globotriaosylceramide (Gb3) throughout the body leading to irreversible target organ damage. As the role of secondary mediators (inflammatory molecules) and their mechanisms has not been fully elucidated, we focused on the interleukin (IL)-6 system in adult FD patients and in matched healthy subjects. To obtain insights into the complex regulation of IL-6 actions, we used a novel approach that integrates information from plasma and exosomes of FD patients (n = 20) and of healthy controls (n = 15). Soluble IL-6 receptor (sIL-6R) levels were measured in plasma with the ELISA method, and membrane-bound IL-6R was quantified in plasma and urinary exosomes using flow cytometry. In FD patients, the levels of soluble IL-6R in plasma were higher than in control subjects (28.0 ± 5.4 ng/mL vs. 18.9 ± 5.4 ng/mL, p < 0.0001); they were also higher in FD subjects with the classical form as compared to those with the late-onset form of the disease (36.0 ± 11.4 ng/mL vs. 26.1 ± 4.5 ng/mL, p < 0.0001). The percentage of urinary exosomes positive for IL-6R was slightly lower in FD (97 ± 1 vs. 100 ± 0% of events positive for IL-6R, p < 0.05); plasma IL-6 levels were not increased. These results suggest a potential role of IL-6 in triggering the inflammatory response in FD. As in FD patients only the levels of sIL-6Rs are consistently higher than in healthy controls, the IL-6 pathogenic signal seems to prevail over the homeostatic one, suggesting a potential mechanism causing multi-systemic damage in FD.

show abstract

“…Among them, pro-inflammatory signaling activation with TNF-α and IL-6 production has been indicated as a potent trigger of ubiquitin ATP-dependent proteasome (UPP response) in the skeletal muscle causing muscular loss ( 53 ). Fabry disease was associated with elevated serum levels of IL-6 and TNF-α, and their levels strongly correlated with MSSI scores reflecting a greater disease burden ( 54 ).…”

Section: The “Metabolic Hypothesis”mentioning

confidence: 99%

Fatigue as hallmark of Fabry disease: role of bioenergetic alterations

Gambardella,

Riccio,

Bianco

et al. 2024

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Fabry disease (FD) is a lysosomal storage disorder due to the impaired activity of the α-galactosidase A (GLA) enzyme which induces Gb3 deposition and multiorgan dysfunction. Exercise intolerance and fatigue are frequent and early findings in FD patients, representing a self-standing clinical phenotype with a significant impact on the patient's quality of life. Several determinants can trigger fatigability in Fabry patients, including psychological factors, cardiopulmonary dysfunctions, and primary alterations of skeletal muscle. The “metabolic hypothesis” to explain skeletal muscle symptoms and fatigability in Fabry patients is growing acknowledged. In this report, we will focus on the primary alterations of the motor system emphasizing the role of skeletal muscle metabolic disarrangement in determining the altered exercise tolerance in Fabry patients. We will discuss the most recent findings about the metabolic profile associated with Fabry disease offering new insights for diagnosis, management, and therapy.

show abstract

Increased Serum Interleukin-6 and Tumor Necrosis Factor Alpha Levels in Fabry Disease: Correlation with Disease Burden

Cited by 8 publications

References 25 publications

Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression

Inflammatory and Cardiovascular Biomarkers to Monitor Fabry Disease Progression

Increased Soluble Interleukin 6 Receptors in Fabry Disease

Fatigue as hallmark of Fabry disease: role of bioenergetic alterations

Contact Info

Product

Resources

About