IL-2 gene polymorphisms affect tacrolimus response in myasthenia gravis

Yang, Shaobo; Li, Yi; Meng, Huanyu; Li, Zhibin; Wu, Jin; Xu, Liqun; Yang, Huan

doi:10.1007/s00228-019-02642-z

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…However, VEGF was more significantly associated with EOMG. It has been found in many studies that IL-2 is elevated in the serum of MG patients, and the receptor of IL-2 has great potential in the current field of immunotherapy research [52,53], which validates the results of this investigation. However, MCP1, MCAF, and VEGF have not been reported in MG studies, which may be the direction for further experimental verification.…”

Section: Myasthenia Gravis and Cytokinessupporting

confidence: 85%

Mendelian randomization analyses of known and suspected risk factors and biomarkers for myasthenia gravis overall and by subtypes

Wang,

Ge,

Feng

et al. 2024

BMC Neurol

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Background Myasthenia gravis (MG) is an autoimmune disease that affects neuromuscular junction. The literature suggests the involvement of circulating cytokines (CK), gut microbiota (GM), and serum metabolites (SM) with MG. However, this research is limited to observational trials, and comprehensive causal relationship studies have not been conducted. Based on published datasets, this investigation employed Mendelian Randomization (MR) to analyze the known and suspected risk factors and biomarkers causal association of MG and its subtypes. Methods This research used two-sample MR and linkage disequilibrium score (LDSC) regression of multiple datasets to aggregate datasets acquired from the genome-wide association studies (GWAS) to assess the association of MG with 41-CK, 221-GM, and 486-SM. For sensitivity analysis and to validate the robustness of the acquired data, six methods were utilized, including MR-Egger regression, inverse variance weighting (IVW), weighted median, and MR-PRESSO. Results The MR method identified 20 factors significantly associated with MG, including 2 CKs, 6 GMs, and 9 SMs. Further analysis of the factors related to the two MG subtypes, early-onset MG (EOMG) and late-onset MG (LOMG), showed that EOMG had a high overlap with MG in the intestinal flora, while LOMG had a greater similarity in CKs and SMs. Furthermore, LDSC regression analysis indicated that Peptococcaceae, oxidized biliverdin, and Kynurenine had significant genetic correlations with general MG, whereas EOMG was highly correlated with Intestinibacter, while LOMG had significant genetic associations with Kynurenine and Glucose. Conclusion This research furnishes evidence for the potential causal associations of various risk factors with MG and indicates a heterogeneous relationship between CKs, GMs, and SMs with MG subtypes.

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Section: Myasthenia Gravis and Cytokinessupporting

confidence: 85%

Mendelian randomization analyses of known and suspected risk factors and biomarkers for myasthenia gravis overall and by subtypes

Wang,

Ge,

Feng

et al. 2024

BMC Neurol

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“…31,32 The multivariate logistic regression results showed that FK506 concentration was not associated with clinical efficacy (p>0.05), consistent with the findings of previous studies in our laboratory. 29,33 We also found that the clinical outcome between group A, group B and group C was not significantly different (p=0.278). The proportion of co-administration of WZC between effective group and ineffective group did not significantly differ (p=0.185).…”

mentioning

confidence: 63%

Clinical Evaluation of the Efficacy and Safety of Co-Administration of Wuzhi Capsule and Tacrolimus in Adult Chinese Patients with Myasthenia Gravis

Peng¹,

Jiang²,

Zhou³

et al. 2021

NDT

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Background: Tacrolimus has been recommended as an effective immunosuppressant for patients with myasthenia gravis (MG), while the high price, variable bioavailability, and narrow therapeutic window restrict its clinical application. Wuzhi capsule (WZC) could improve tacrolimus blood concentration by inhibiting the metabolism of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp). There are few studies focused on the coadministration of WZC and tacrolimus in autoimmune diseases. This study was aimed at quantifying the efficacy and safety of coadministration of WZC and tacrolimus in adult Chinese patients with MG. Methods: In this retrospective study, 122 patients with MG on tacrolimus were enrolled. The initial tacrolimus dose was 2 mg/d. Patients with standard initial tacrolimus concentration were classified into group A (standard-dose group). Those failed to reach target concentration were divided into group B (high-dose group) and group C (co-administering WZC group), according to treatment adjustment of increasing tacrolimus dose and coadministration of WZC, respectively. A logistic analysis was used to identify factors associated with clinical outcome. Adverse drug reactions (ADRs) were recorded for safety analysis. Results: The tacrolimus concentration after coadministration of WZC was remarkably increased. It was higher compared with simply increasing the tacrolimus dose (p<0.001). The multivariate logistic analysis indicated that the baseline quantitative MG score was a predictive factor for clinical outcomes (OR=0.189; 95% CI 0.082-0.436; p<0.001). Fourteen patients (11.5%) reported ADRs after tacrolimus therapy. ADRs incidence was not related to WZC coadministration. Conclusion:The coadministration of WZC and tacrolimus can substantially elevate the tacrolimus concentration. It is a safe and economic treatment for adult Chinese patients with MG. Patients with a worse disease condition tend to present a better clinical outcome after tacrolimus therapy.

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“…In addition, other studies have found that patient response to tacrolimus is influenced by pharmacogenetics. MG patients with rs2069762 G/T and G/G genotype and TAGG haplotype for interleukin-2 gene tend to have a poor response to tacrolimus [ 28 ]. And the multiple single nucleotide polymorphisms on CYP3A4, CYP3A5, FKBP1A, and NFATC2 genes involved in the pharmacokinetics and pharmacodynamics of tacrolimus are closely related to therapeutic effect [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus as Single-Agent Immunotherapy and Minimal Manifestation Status in Nonthymoma Myasthenia Gravis

Duan

Peng

et al. 2021

Journal of Immunology Research

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Background. Tacrolimus is a second-line immunosuppressant in myasthenia gravis (MG) therapy, which is mainly used in combination with corticosteroids to reduce steroid dose and maintain the effect of immunotherapy. However, few studies have focused on the effect of tacrolimus as single-agent immunotherapy on achieving minimal manifestation status (MMS). Thus, this study is aimed at exploring the efficacy and influencing factors of tacrolimus as single-agent immunotherapy in MG. Methods. Clinical data of 75 nonthymoma MG patients treated with tacrolimus single-agent as initial immunotherapy were retrospectively analyzed. The therapeutic effect was evaluated by Myasthenia Gravis Foundation of America postintervention status. Clinical factors affecting the achievement of MMS and treatment reactivity of different MG subtypes were determined by Cox regression analysis. Results. Tacrolimus was generally safe, with only two patients (2.7%) switching medications due to side effects. 32% of patients had improved symptoms after 1 month of treatment. 69.2% of patients achieved MMS or better after one year. The age < 39 years old, QMG score < 11 points, and AChR − Ab titer < 8.07 nmol / L were indicative of a favorable response, which was independent of gender, course of the disease. As for MG subtypes, ocular and seronegative MG showed better treatment sensitivity. Conclusions. Tacrolimus as single-agent immunotherapy takes effect quickly and can effectively enable nonthymoma MG patients to achieve MMS. Tacrolimus can be used alone for the initial immunotherapy of MG patients, especially for young, mild, and low antibody titer patients.

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IL-2 gene polymorphisms affect tacrolimus response in myasthenia gravis

Cited by 7 publications

References 27 publications

Mendelian randomization analyses of known and suspected risk factors and biomarkers for myasthenia gravis overall and by subtypes

Mendelian randomization analyses of known and suspected risk factors and biomarkers for myasthenia gravis overall and by subtypes

Clinical Evaluation of the Efficacy and Safety of Co-Administration of Wuzhi Capsule and Tacrolimus in Adult Chinese Patients with Myasthenia Gravis

Tacrolimus as Single-Agent Immunotherapy and Minimal Manifestation Status in Nonthymoma Myasthenia Gravis

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