Immune dysregulation in chronic inflammatory demyelinating polyneuropathy.

OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disorder of the peripheral nerves with an incompletely understood underlying pathophysiology. This investigation focused on defining B and T cell frequencies, T cell functional capacity and innate immune system analysis in patients with CIDP. METHODS: By using multi-parameter flow cytometry, we examined the phenotype and function of PBMCs in 25 CIDP patients who were relatively clinically stable on treatment who met EFNS/PNS criteria, 21 patients with genetically confirmed hereditary neuropathy and 25 healthy controls. We also evaluated the regulatory T cell (Treg) inhibitory capacity by co-culturing Treg and effector T cells. RESULTS: Proinflammatory CD4 T cells, especially type 1 helper T cell (Th1) and CD8 T cells in patients with CIDP were found to have an enhanced capacity to produce inflammatory cytokines. There was no difference in frequency of Th17 regulatory cells in CIDP patients versus healthy controls, however, Treg function was impaired in CIDP patients. There was no remarkable difference in innate immune system measures. Within B cell subsets, transitional cell frequency was decreased in CIDP patients. INTERPRETATION: Patients with CIDP clinically stable on treatment continued to show evidence of a proinflammatory state with impaired Treg function. This potentially implies an inadequate suppression of ongoing inflammation not addressed by standard of care therapies as well as persistent activity of disease while on treatment. Targeting T cells, especially inhibiting Th1 and polyfunctional CD8 T cells or improving Treg cell function could be potential targets for future therapeutic research.

Palmdelphin Deficiency Evokes NF-κB Signaling in Valvular Endothelial Cells and Aggravates Aortic Valvular Remodeling.

Palmd-deficient mice of advanced age manifest increased aortic valve peak velocity, thickened aortic valve leaflets, and excessive extracellular matrix deposition, which are key features of calcific aortic valve disease. PALMD is predominantly expressed in endothelial cells of aortic valves, and PALMD-silenced valvular endothelial cells are prone to oscillatory shear stress-induced endothelial-to-mesenchymal transition. Mechanistically, PALMD is associated with TNFAIP3 interaction protein 1, a binding protein of TNFAIP3 and IKBKG in NF-κB signaling. Loss of PALMD impairs TNFAIP3-dependent deubiquitinating activity and promotes the ubiquitination of IKBKG and subsequent NF-κB activation. Adeno-associated virus-mediated PALMD overexpression ameliorates aortic valvular remodeling in mice with calcific aortic valve disease, indicating protection.

Corrigendum: Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients.

[This corrects the article DOI: 10.3389/fneur.2022.961628.].

Fibroblast growth factor 21 inhibits vascular calcification by ameliorating oxidative stress of vascular smooth muscle cells.

Vascular calcification is very common in clinical. Severe vascular calcification is related to the occurrence of adverse events. Oxidative stress (OS) plays a pathophysiological role in the formation of vascular calcification. Previous studies have demonstrated that fibroblast growth factor 21(FGF21) could inhibit vascular calcification both in vivo and in vitro. FGF21 has also been proved to promote the recovery of superoxide dismutase (SOD) and thereby alleviate OS. Thus, our assumption was that FGF21 inhibit vascular calcification partly by restoring the level of antioxidant SOD and reducing OS. In this study, we established the vascular calcification by 5/6 nephrectomy plus high phosphate diet chronic kidney disease (CKD) model. The results showed the receptor of FGF21, fibroblast growth factor receptor 1 (FGFR1) and ßKlotho in the aorta increased in CKD group, and mainly located in the media of the artery. Ulteriorly, immunofluorescence (IF) and IHC staining showed that FGFR1 and ßKlotho mainly existed in arterial vascular smooth muscle cells (VSMCs). When FGF21 was knock out, the calcification was more severe in FGF21 KO + CKD mice, compared to wild type (WT)+ CKD mice. The transcriptional level of vascular calcification-related genes was significantly higher in FGF21 KO mice than control group. The dihydroethidium (DHE) staining reactive oxygen species (ROS) level in the CKD group was higher compared to the control group, but lower in FGF21 KO + CKD group, and the transcriptional level of SOD1 and SOD2 in FGF21 KO + CKD group was significantly higher than that in CKD group. In conclusion, FGF21 could inhibit vascular calcification, partly by restoring the level of antioxidant SOD and reducing vascular oxidative stress. This study provides further evidence for FGF21 as a candidate drug for cardiovascular protective agents.

Integration of two-stage anaerobic digestion process with in situ biogas upgrading.

High impurity concentration of biogas limits its wide commercial utilization. Therefore, the integration of two-stage anaerobic digestion process with in situ biogas upgrading technologies is reviewed, with emphasis on their principles, main influencing factors, research success, and technical challenges. The crucial factors that influence these technologies are pH, alkalinity, and hydrogenotrophic methanogenesis. Hence, pH fluctuation and low gas-liquid mass transfer of H2 are some major technical challenges limiting the full-scale application of in situ upgrading techniques. Two-stage anaerobic digestion integration with various in situ upgrading techniques to form a hybrid system is proposed to overcome the constraints and systematically guide future research design and advance the development and commercialization of these techniques. This review intends to provide the current state of in situ biogas upgrading technologies and identify knowledge gaps that warrant further investigation to advance their development and practical implementation.

Effect of high-sensitivity C-reactive protein on the relationship between haemoglobin A1c and cardiovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cohort study.

Background: There are different opinions on haemoglobin A1c (HbA1c) in predicting cardiovascular events after percutaneous coronary intervention (PCI). Some factors may affect the ability of HbA1c to predict cardiovascular events, resulting in this inconsistency. Inflammation is a direct and whole-process participant in atherosclerosis. However, no one has studied the effect of inflammation on the correlation between HbA1c and cardiovascular events. Therefore, we aimed to test the hypothesis that high-sensitivity C-reactive protein (hsCRP) modulates HbA1c-related cardiovascular events in patients with the acute coronary syndrome (ACS) undergoing PCI. Methods: This was a retrospective cohort study. We enrolled patients with ACS who were hospitalized for PCI and followed up for 24 months. The primary outcome was the composite of major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization. We stratified the overall population by HbA1c tertiles and hsCRP median. The relationship between HbA1c, hsCRP, and cardiovascular events was analysed by the Cox proportional hazard regression model. Results: A total of 2,023 patients were enrolled in this study (age: 59.7±10.03 years old, 78.1% male patients). After the 24-month follow-up, 152 (7.51%) events occurred. Patients with hsCRP >1.21 mg/L had an increased cardiovascular risk compared with patients with hsCRP ≤1.21 mg/L [hazard ratio (HR) 1.58, 95% confidence interval (CI): 1.12-2.24, P=0.010]. We did not observe a significant correlation between HbA1c and cardiovascular events. Furthermore, we stratified patients by hsCRP ≤1.21 or >1.21 mg/L and found that the correlation between HbA1c and cardiovascular events was only significant in patients with hsCRP ≤1.21 mg/L (tertile 2 vs. tertile 1: HR 1.76, 95% CI: 0.79-3.90, P=0.165, tertile 3 vs. tertile 1: HR 3.03, 95% CI: 1.50-6.12, P=0.002; P=0.008 for trend) but not in patients with hsCRP >1.21 mg/L. Conclusions: This study showed that hsCRP may affect the relationship between HbA1c and the risk of cardiovascular events in patients with ACS after PCI. This finding suggests that the risk of cardiovascular events may be underestimated when only HbA1c is used as a predictor of cardiovascular risk. HbA1c has a better predictive value in the absence or low levels of inflammation states represented by hsCRP as a predictor of cardiovascular events.

Leflunomide combined with low-dose prednisone inhibits proinflammatory T cells responses in myasthenia gravis patients.

We previously found that leflunomide combined with low-dose prednisone rapidly improved the clinical symptoms of myasthenia gravis (MG), but we had not investigated the mechanism of this phenomenon. This study documents the effect of leflunomide combined with low-dose prednisone on pro-inflammatory T cells in MG patients. We compared 32 treated MG patients with 18 controls. We collected peripheral blood before treatment and 4, 8, and 12 weeks after treatment. We extracted peripheral blood mononuclear cells (PBMCs) and stimulated them with phorbol 12-myristate 13-acetate (PMA) + ionomycin and quantified IFN-γ, IL-4, IL-17, and IL-9 secretion through ELISA. We quantified T helper (Th) cells Th1 (CD3+CD4+IFN-γ+), Th2 (CD3+CD4+IL-4+), Th17 (CD3+CD4+IL-17A+) and Th9 (CD3+CD4+IL-9+) among PBMCs. The treatment significantly reduced IL-17 and IL-9 secretion in peripheral blood but did not affect IFN-γ levels. Significant decreases in IL-17 and IL-9 appeared at week 12, and the trend of change was similar to that of the MG composite score. Flow cytometry indicated that leflunomide combined with low-dose prednisone significantly reduced the frequency of Th1 and Th17 cells. These findings demonstrate the potential of this treatment as an alternative immunosuppressive therapy for MG.

The predictive value of the triglyceride-glucose index for cardiovascular events in patients with coronary chronic total occlusion.

BACKGROUND: Chronic total occlusion (CTO) of the coronary artery is a difficult problem in clinical practice. The triglyceride-glucose (TyG) index is an effective risk predictor of cardiovascular risk. However, the relationship between the TyG index and the prognosis of CTO patients remains unstudied. Thus, the present study aimed to investigate the relationship between the TyG index and cardiovascular risk in CTO patients. METHODS: This was a single-centre, retrospective cohort study. We retrospectively enrolled 652 patients with CTO lesions diagnosed by angiography and who underwent revascularization through PCI. Patients were routinely followed up for 24 months unless meeting the endpoint. The primary endpoint was the composite of all-cause death, nonfatal myocardial infarction, unplanned revascularization, and nonfatal ischaemic stroke. To test the association of the TyG index with cardiovascular risk, the categorized TyG index and Cox proportional hazards regression models were utilized. RESULTS: A total of 652 patients were enrolled in the final analysis (male: 83.7%, age: 58.2 ± 10.49 years). The average TyG index was 8.8 ± 0.57. CTO PCIs were procedurally successfully completed in 503 (77.15%) patients. During the follow-up period of 22.8 ± 3.84 months, 73 (11.19%) major adverse cardiovascular and cerebral events (MACCEs) occurred. When fully adjusted, there was a 2.09-fold risk for MACCEs among patients with the highest TyG index compared with those with the lowest TyG index [T2 vs. T1: hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.65-2.38, P = 0.057; T3 vs. T1: HR 2.09, 95% CI 1.14-3.86, P = 0.018; P for trend = 0.036]. The restricted cubic spline (RCS) analysis showed that the HR for MACCEs increased as the TyG index increased over 8.71 [HR per standard deviation (SD) 1.740, 95% CI 1.23-2.46, P = 0.002]. The risk of MACCEs increased with increasing tertiles of TyG index in successful CTO PCI patients and nondiabetes mellitus (DM) patients (P < 0.05) but not in patients with failed CTO PCI and DM patients. CONCLUSION: The study revealed that the TyG index had significant relevance to cardiovascular risk in CTO patients and suggests that the TyG index is feasible for predicting cardiovascular risk in CTO patients.

[Fibroblast growth factor 21 plays a protective role in cardiovascular diseases by inducing autophagy].

Fibroblast growth factor 21 (FGF21) is a growth factor with endocrine function in the fibroblast growth factor family. Previous reports have shown that FGF21 is involved in the regulation of energy metabolism and plays a protective role in cardiovascular diseases such as coronary heart disease, diabetes, non-alcoholic fatty liver disease and so on. Recent studies have found that FGF21 can induce autophagy in a variety of tissues and organs, and autophagy is involved in many pathological processes of cardiovascular diseases, including vascular calcification, atherosclerosis, and myocardial ischemia-reperfusion injury. Therefore, FGF21 may play a protective role in a variety of cardiovascular diseases by regulating autophagy. This article reviews the research progress on the protective role of FGF21 in cardiovascular diseases by inducing autophagy.

Risk factors for cardiac rupture after acute ST-segment elevation myocardial infarction during the percutaneous coronary intervention era: a retrospective case-control study.

Background: In percutaneous coronary intervention (PCI) era, more clinically valuable risk factors are still needed to determine the occurrence of cardiac rupture (CR). Therefore, we aimed to provide evidence for the early identification of CR in ST-segment elevation myocardial infarction (STEMI). Methods: A total of 22,016 consecutive patients with STEMI admitted to Cangzhou Central Hospital and Tianjin Chest Hospital from January 2013 to July 2021 were retrospectively included, among which 195 patients with CR were included as CR group. From the rest 21,820 STEMI patients without CR, 390 patients at a ratio of 1:2 were included as the control group. A total of 66 patients accepted PCI in the CR group, and 132 patients who accepted PCI in the control group at a ratio of 1:2 were included. The status of first medical contact, laboratory examinations, and PCI characteristics were recorded. Multivariate logistic regression analysis was used to investigate the risk factors related to CR. Results: There was a higher proportion of patients with myocardial infarction (MI) in the high lateral wall in the CR group (23.6% vs. 8.2%, P<0.001). The proportion of single lesions was lower in the CR group (24.2% vs. 45.5%, P=0.004). Female (OR =2.318, 95% CI: 1.431-3.754, P=0.001), age (OR =1.066, 95% CI: 1.041-1.093, P<0.001), smoking (OR =1.750, 95% CI: 1.086-2.820, P=0.022), total chest pain time (OR =1.017, 95% CI: 1.000-1.035, P=0.049), recurrent acute chest pain (OR =2.750, 95% CI: 1.535-4.927, P=0.001), acute myocardial infarction (AMI) in the high lateral wall indicated by ECG (OR =5.527, 95% CI: 2.798-10.918, P<0.001), acute heart failure (OR =3.585, 95% CI: 2.074-6.195, P<0.001), and NT-proBNP level (OR =1.000, 95% CI: 1.000-1.000, P=0.023) were risk factors for CR in all patients. In patients who accepted PCI, single lesion (OR =0.421, 95% CI: 0.204-0.867, P=0.019), preoperative thrombolysis in myocardial infarction (TIMI) grade (OR =0.358, 95% CI: 0.169-0.760, P=0.007), and postoperative TIMI grade (OR =0.222, 95% CI: 0.090-0.546, P=0.001) were risk factors for CR. Conclusions: Non-single lesions and preoperative and postoperative TIMI grades were risk factors for CR in patients who accepted PCI. In addition to previously reported indicators, we found that AMI in the high lateral wall maybe helpful in early and accurate identification and prevention of possible CR.

Possible effects of fibroblast growth factor 21 on vascular calcification via suppressing activating transcription factor 4 mediated apoptosis and osteogenic transformation in rats.

Vascular calcification (VC), a significant risk factor of many cardio-cerebral vascular diseases, is a perplexing issue with no effective treatment in clinical work up to now. Endoplasmic reticulum stress (ERS) mediated apoptosis has been proved to be a significant mechanism for initiating VC process. Activating transcription factor 4 (ATF4), a key transcription factor of ERS, is most closely associated with VC. Fibroblast growth factor 21 (FGF21), an atypical member of the FGFs family, has a protective biological function in various metabolic diseases by ERS pathways. However, the possible effects of FGF21 on VC by regulating ERS, especially through the ATF4 pathway, is still unclear. Our research provides the first evidence that exogenous FGF21 treatment can alleviate the vitamin D3 plus nicotine-induced VC at least in part via suppressing ATF4 mediated apoptosis and osteogenic transformation in rats.

The clinical need for clustered AChR cell-based assay testing of seronegative MG.

Trial eligibility in myasthenia gravis (MG) remains largely dependent on a positive autoantibody serostatus. This significantly hinders seronegative MG (SNMG) patients from receiving potentially beneficial new treatments. In a subset of SNMG patients, acetylcholine receptor (AChR) autoantibodies are detectable by a clustered AChR cell-based assay (CBA). Of 99 SNMG patients from two academic U.S. centers, 18 (18.2%) tested positive by this assay. Autoantibody positivity was further validated in 17/18 patients. In a complementary experiment, circulating AChR-specific B cells were identified in a CBA-positive SNMG patient. These findings corroborate the clinical need for clustered AChR CBA testing when evaluating SNMG patients.

Investigation of product selectivity and kinetics of poplar sawdust catalytic pyrolysis over bi-metallic Iron-Nickel/ZSM-5 catalyst.

Py-GC/MS and thermogravimetric analysis were carried out to systematically explore product selectivity and kinetics of poplar sawdust catalytic pyrolysis over bi-metallic Fe-Ni/ZSM-5. The results showed that the Fe-Ni/ZSM-5 exhibited an additive effect on the production of monocyclic aromatic hydrocarbons compared to mono-metallic catalysts (Fe/ZSM-5 or Ni/ZSM-5). Fe-Ni/ZSM-5 further increased the yield of toluene (17.28 mg g-1), which was 41.4% and 80.9% higher than Fe/ZSM-5 and Ni/ZSM-5, respectively. According to the kinetic analysis, the average activation energy obtained from catalytic pyrolysis with Fe-Ni/ZSM-5 using the methods of Friedman, Starink, Flynn-Wall-Ozawa, and Kissinger-Akahira-Sunose was 156.19, 152.39, 154.30, and 152.11 kJ mol-1, respectively. Fe-Ni/ZSM-5 addition lowered the activation energy compared to non-catalytic pyrolysis at the conversion rate of 0.15-0.75. The overall catalytic pyrolysis process of poplar sawdust follows the diffusion and nucleation models. The thermodynamic parameters (enthalpy and entropy) showed positive and negative values, respectively, indicating non-spontaneous reactions during the catalytic pyrolysis process.

Cellular changes in eculizumab early responders with generalized myasthenia gravis.

Eculizumab (ECU), a C5 complement inhibitor, is approved to treat acetylcholine receptor autoantibody positive generalized myasthenia gravis (AChR MG). The clinical effect of ECU relies on inhibition of the terminal complement complex; however, the effect of ECU on lymphocytes is largely unknown. We evaluated innate and adaptive immunity among AChR MG patients (N = 3) before ECU and ≥3 months later while on stable therapy, and found reduced activation markers in memory CD4+ T cell subsets, increased regulatory T cell populations, and reduced frequencies of CXCR5+HLA-DR+CCR7+ Tfh subsets and CD11b+ migratory memory B cells. We observed increases within CD8+ T cell subsets that were terminally differentiated and senescent. Our data suggest complement inhibition with ECU modulates the adaptive immunity in patients with MG, consistent with preclinical data showing changes in complement-mediated signaling by T- and antigen-presenting cells. These findings extend our understanding of ECU's mechanism of action when treating patients with MG.

Normative dataset for plasma cytokines in healthy human adults.

We determined normative data for plasma cytokines established from a cohort of 126 carefully screened healthy adults aged 18 to 64 years. Participants were enrolled to ensure an even age and sex distribution and to include at least 30% non-Caucasians. Plasma cytokines for 18 analytes were tested by multiplex immunoassay. The data are presented by age cohort (18-29 years, 30-39, 40-49, and 50-66), as well as by sex and racial background. This dataset complements published normative ranges of cellular subsets generated by comprehensive polychromatic flow cytometry analysis of the healthy human immune system [1]. These data are available to researchers and have value as a reference range for research involving peripheral cytokines.

Knowledge and perceptions of the COVID-19 pandemic among patients with myasthenia gravis.

BACKGROUND: Patients with myasthenia gravis (MG) may be particularly vulnerable during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic due to risk of worsening disease during infection, potential adverse impacts of coronavirus disease 2019 (COVID-19) treatments on neuromuscular transmission, and a limited ability to fight off infection related to immunosuppressive treatments. Our goal is to understand how patients are experiencing the COVID-19 pandemic, including where they receive relevant information, how it has affected medical care, and what measures they use to protect themselves. METHODS: This is a prospective online survey study at large academic practice. All patients with a neuromuscular junction disorder diagnosis code in the Duke Health System were invited to participate. RESULTS: One thousand eight hundred and forty eight patients were approached to participate and 75 completed the survey between 16 April 2020 and 28 May 2020. The most frequently used information sources were non-presidential federal government (75%), state government (57%), local healthcare provider (37%), and television news (36%). Non-presidential federal government (80%), local healthcare providers (55%), state government (33%), and patient support organizations (29%) were considered the most trusted information sources. Thirty-three (44%) of survey responders had attended a telemedicine visit. Patients were taking recommended precautions during the pandemic and remained very concerned (69%) about COVID-19. Generalized Anxiety Disorder-7 scores were moderate-severe in 20% of responders. CONCLUSIONS: Healthcare providers, the government, and patient organizations play a critical role in communicating with the MG patient community. Use of targeted messaging strategies by these groups to convey accurate information may increase effectiveness and lead to more informed patients with reduced anxiety.

Comparison of transradial coronary intervention for left main bifurcation disease using the new Braidin® slender 7 Fr sheath and a standard 6 Fr sheath.

OBJECTIVES: To compare the effectiveness and safety of the Braidin® slender 7 Fr sheath with a standard 6 Fr sheath for treating left main bifurcation disease. METHODS: From January 2017 to March 2019, 277 patients with left main bifurcation disease who underwent the transradial approach for percutaneous coronary intervention were divided into the slender 7 Fr sheath group (Braidin® slender 7 Fr sheath, n = 154) and standard 6 Fr sheath group (n = 123). Pathological features, surgical effect, and complications were evaluated. RESULTS: The rate of using the classic crush technique was significantly higher in the slender 7 Fr sheath group than in the standard 6 Fr sheath group. The slender 7 Fr sheath group had a significantly shorter operation time than the standard 6 Fr sheath group. There were no significant differences in the radial artery occlusion rate after surgery and at 1 month of follow-up between the groups. Multivariate logistic regression analysis showed that 6 Fr and Braidin slender 7 Fr sheaths did not predict radial artery occlusion. CONCLUSION: The Braidin slender 7 Fr sheath has a superior operative process and similar safety for the radial artery as that of the standard 6 Fr sheath for treating left main bifurcation disease.

Clinical effectiveness and radial artery remodeling assessment via very-high-frequency ultrasound/ultra biomicroscopy after applying slender 7Fr sheath for transradial approach in left main bifurcation disease.

OBJECTIVE: To explore the clinical effect and radial remodeling of transradial slender 7 Fr sheath for left main bifurcation disease (LM bifurcation). METHODS: From January 2018 to September 2019, 236 patients with LM bifurcation undergoing transradial percutaneous coronary intervention (PCI) from two heart centers were divided into slender 7 Fr sheath group (n = 127) and 6 Fr sheath group (n = 109). Quantitative coronary angiography (QCA) and very high-frequency ultrasound/ultra biomicroscopy (VHFUBM) were used to assess the clinical effect and radial remodeling of transradial sheath. RESULTS: Slender 7 Fr sheath group had a higher preoperative distal bifurcation angle (67.271 ± 22.886) than 6 Fr group (55.831 ± 20.245) (p < .05). Post-PCI QCA results showed significant differences in minimum lumen diameter at proximal left anterior descending artery (LAD) and left circumflex artery (LCX) between two groups (p < .05). There were no significant differences in target vessel myocardial infarction, target vessel revascularization, death and major adverse cardiocerebrovascular events (MACCE) at 30-day and 1-year follow-up between two groups (p>.05). No significant differences were observed in radial artery diameter (RAD), intimal-medial thickness (IMT) and radial artery injury at 24-h and 90-day follow-up between two groups. CONCLUSION: With larger main and side branch diameter, larger angle of bifurcation and higher SYNTAX score, transradial slender 7 Fr sheath obtained similar clinical effects as 6 Fr sheath without increasing the occurrence of adverse events. Similar follow-up RAD, IMT and radial artery injury were observed. Therefore, slender 7 Fr sheath has safety and feasibility in applying to transradial LM-Bifurcation PCI.

Imbalance in T follicular helper cells producing IL-17 promotes pro-inflammatory responses in MuSK antibody positive myasthenia gravis.

A detailed understanding of the role of Tfh cells in MuSK-antibody positive myasthenia gravis (MuSK-MG) is lacking. We characterized phenotype and function of Tfh cells in MuSK-MG patients and controls. We found similar overall Tfh and follicular regulatory (Tfr) T cell frequencies in MuSK-MG and healthy controls, but MuSK-MG patients exhibited higher frequencies of Tfh17 cells and a higher ratio of Tfh:Tfr cells. These results suggest imbalanced Tfh cell regulation, further supported by increased frequencies of CD4 T cells co-producing IL-21/IL-17 and IL-17/IFN-γ, and increased Tfh-supported IgG production. These results support a role for Tfh cell dysregulation in MuSK-MG immunopathology.