Micro uidic devices are powerful bioapplication tools for cellular experiments in particular, as they can regulate physical and chemical parameters such as the ow rate, shear stress, oxygen, and molecular concentrations in a culture medium to mimic physiological and pathological microenvironments in vitro. However, as cell cultures take place in enclosed spaces, culture samples have to be removed repeatedly to monitor cell-derived metabolites and proteins in order to maintain the cellular microenvironment. We report a simple method for obtaining surface enhanced Raman scattering (SERS) spectra through self-assembly of a nanoparticle monolayer on polydimethylsiloxane (PDMS), which is commonly used in highly biocompatible micro uidic devices. Silica nanoparticles were stabilized as a hexagonal close packed structure on an O 2 plasma-processed PDMS membrane, and was coated with silver using vapor deposition to create an SERS plate. When this SERS plate was installed in a micro uidic device, the nanoparticles did not peel off even after long-term uid immersion. The SERS spectra exhibited stable SERS generation and an enhancement factor of more than 1.5 × 10 6 of the Raman signals from rhodamine 6G compared to the signals without nanoparticles. The SERS spectra of lactate and ATP were obtained, and Raman shifts due to the different masses of 12 C-and 13 C-lactate were observed, suggesting that the proposed method can be applied to determine the cellular metabolic ux in micro uidic devices. We also obtained cell membrane-derived SERS spectra by culturing murine mammary carcinoma 4T1 cells directly on the nanoparticle membrane. PDMS has high biocompatibility and is often used for fabricating micro uidic devices. Through tight binding of the nanoparticles to the O 2 plasma-treated PDMS, the chemical reaction products or the metabolites from cells can be measured for a long duration, while maintaining the microenvironment. We anticipate that this technology can be utilized as a useful tool for analyzing cellular metabolic functions and imaging cellular distributions without staining in various pathological models created in micro uidic devices.
BackgroundPeripheral neuropathy is one of major manifestations of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and has a significant impingement on patients’ quality of life.1,2ObjectivesThe aim of this study was to clarify clinical features of AAV patients with peripheral neuropathy and identify risk factors for severe motor neuropathy.MethodsAll consecutive patients with active, treatment-naïve AAV who were admitted to our hospital between April, 2012 and October, 2021 were reviewed. Patients were divided into two groups according to the presence or absence of peripheral neuropathy, and their baseline clinical characteristics were compared.ResultsA total of 76 patients (microscopic polyangiitis, MPA, n=37, granulomatosis with poly angiitis, GPA, n=24, eosinophilic GPA, EGPA, n=15) were included in the study. Among them, 28 patients (36.8%) had peripheral neuropathy including 12 with MPA, 4 with GPA, and 12 with EGPA. The clinical characteristics of all patients with peripheral neuropathy were younger age (66.0 years versus 74.5 years, p<0.05) and showed higher white blood cell counts (11500/μL versus 8800/μL, p<0.05), higher blood eosinophil counts (788.5/μL versus 139.0/μL, p<0.05), higher creatinine clearance (77.3 mL/min versus 56.3 mL/min, p<0.05), higher levels of serum immunoglobulin (Ig)E (660 IU/mL versus 125 IU/mL, p<0.05), and IgG4 (361.5 mg/dL versus 84.0 mg/dL, p <0.05). In patients with EGPA, the most susceptible type to peripheral neuropathy, 80% of the patients had peripheral neuropathy. Comparison between patients with EGPA with peripheral neuropathy and those without demonstrated significantly younger age (56.0 years versus 80.0 years, p<0.05) and higher blood eosinophil counts (7832/μL versus 2340/μL, p<0.05) were characteristic for the presence of peripheral neuropathy. Patients with EGPA with motor neuropathy (n=8) showed higher white blood cell counts (26850//μL versus 8650//μL, p <0.05) and higher blood eosinophil counts (13134//μL versus 3436//μL, p<0.05) compared with those with only sensory neuropathy (n=4).ConclusionOur current study has shown that patients with EGPA are more prone to peripheral neuropathy than patients with MPA or GPA. Severe motor neuropathy was observed only in patients with EGPA and associated with more intense eosinophilic inflammation. Our results suggest that molecular targeted therapy that improves eosinophilic inflammation such as anti-IL-5 therapy is beneficial for peripheral neuropathy.References[1]RUTGERS, Abraham; KALLENBERG, Cees GM. Peripheral neuropathy in AAV—when vasculitis hits a nerve. Nature Reviews Rheumatology, 2012, 8.3: 127-128.[2]NAKAZAWA, Daigo, et al. Pathogenesis and therapeutic interventions for ANCA-associated vasculitis. Nature Reviews Rheumatology, 2019, 15.2: 91-101.Disclosure of InterestsNone declared
BackgroundMyositis-specific autoantibodies are useful biomarkers to make a diagnosis and predict prognosis of idiopathic inflammatory myopathies. Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) is one of the most representative myositis-specific autoantibodies, however, organ involvement in patients positive for anti-ARS is not limited to the muscles but also skin, joints, and lungs, which constructs spectrums of idiopathic inflammatory myopathies called anti-synthetase syndrome. While individual anti-ARS antibodies have been known to form distinct clinical subsets, little is known regarding their chronological clinical presentation patterns and diagnosis during clinical course.ObjectivesTo clarify the clinical characteristics of patients positive for anti-ARS and transition in manifestations and diagnosis during their clinical courses.MethodsWe reviewed consecutive patients with anti-ARS who had visited our hospital between 1998 and 2022 retrospectively. Anti-ARS antibodies were detected and categorized with RNA immunoprecipitation assays. We collected patient clinical characteristics and laboratory parameters including transition of diagnosis, manifestations and, organ involvement from their medical records chronologically. All statistical analyses were performed using JMP 15 (SAS Institute Inc., Cary, NC, USA).ResultsWe included 97 patients positive for anti-ARS in the analysis. The mean age was 53.2 years old, and 73 (75%) were female. The types of anti-ARS Ab were anti-Jo-1 (37%), anti-EJ (32%), anti-PL-7 (11%), anti-PL-12 (12%), anti-KS (4%), and anti-OJ (3%). Half of the patients had co-existing other autoantibodies such as anti-SS-A/Ro, anti-SS-B/La, anti-dsDNA, anti-RNP, and/or rheumatoid factor, but the combination of antibodies was not different among each anti-ARS. The initial diagnoses of the patients were polymyositis (22%), dermatomyositis (33%), amyopathic dermatomyositis (13%), and interstitial pneumonia with autoimmune features (27%). Raynaud’s phenomenon were observed in 25% of the patients; 19% in patients with anti-Jo-1, 36% in anti-EJ, 11% in anti-PL-7, 30% in anti-PL-12, 25% in anti-KS, and 33% in anti-OJ antibodies. Interstitial lung disease was observed in all patients except for three (two with anti-Jo-1 and one with anti-PL-12). Myositis was diagnosed initially in 72% of patients with anti-Jo-1, 50% with anti-EJ, 40% with anti-PL-7, 42% with anti-PL-12, none with anti-KS, and 67% with anti-OJ antibodies, but additional 6%, 4%, 40%, 8%, 0%, and 0% with those individual antibodies, respectively, were diagnosed with myositis during the mean observation period of 9.6 years. Acute or subacute exacerbation of interstitial lung disease requiring immunosuppressive treatment intensification were observed in 28% of patients with anti-Jo-1, 33% with anti-EJ, 40% with anti-PL-7, 8% with anti-PL-12, 33% with anti-KS, and 67% with anti-OJ antibodies.ConclusionAlmost all patients positive for anti-ARS positive had interstitial lung disease irrelevant of myositis diagnosis. Patients with anti-Jo-1 were suffering from typical myositis complicated with interstitial lung diseases at initial diagnosis, while patients with anti PL-7 tended to have precedent interstitial lung disease followed by development of myositis during clinical courses. The incidence of acute exacerbation of interstitial lung disease was the lowest in patients with anti-PL12.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
BackgroundIdiopathic inflammatory myopathies (IIMs) are heterogenous systemic autoimmune disorders that mainly affect the skin, muscles, and lungs. Whereas cardiac involvement is considered to be rare, it causes cardiac inflammation and fibrosis leading to severe morbidity and mortality. However, little is known about clinical characteristics and risk factors for cardiac involvement in patients with IIMs.ObjectivesThe aim of this study was to clarify the frequency and clinical characteristics of cardiac involvement and its risk factors in patients with IIMs.MethodsWe retrospectively reviewed consecutive patients with IIMs who visited Keio University Hospital from 2002 to 2022. We divided patients into two groups according to the presence or absence of symptomatic cardiac involvement and compared their clinical characteristics and autoantibodies between the two groups. We defined symptomatic cardiac involvement as the presence of chest pain, palpitation, cardiogenic leg edema, or respiratory distress accompanied by abnormal findings of cardiac examinations such as electrocardiography, echocardiography, and/or cardiac magnetic resonance imaging (MRI).ResultsWe included 145 patients with IIMs in the analysis. The mean age at IIMs diagnosis was 55 years old, and 71.7% were female. Forty patients (27.6%) were polymyositis, 53 (36.6%) were dermatomyositis, 44 (30.3%) were amyopathic dermatomyositis, and 8 (5.5%) were immune-mediated necrotizing myopathy. Among them, 52 patients (35.9%) had abnormal findings on electrocardiography, echocardiography, and/or cardiac MRI, and 17 (11.7%) were diagnosed with symptomatic cardiac involvement at the mean age of 65 years during the mean observation period of 20.0 years. Comparison of clinical characteristics identified no difference in the mean age, sex distribution, and duration from IIM diagnosis to symptomatic cardiac involvement between the two groups. Also, no significant difference was found in the positivity of anti-amynoacyl tRNA synthetase antibody, anti-MDA5 antibody, and anti-SS-A antibody, IIMs subtypes, presence of skin rash, malignancy, interstitial lung disease, history of cyclophosphamide use, and maximum levels of CK, aldolase, CK-MB, troponin T, and CRP. However, the presence of Raynaud’s phenomenon and neutrophil/lymphocyte ratio at diagnosis were significantly higher in the cardiac involved group compared to the non-cardiac involved group (53.85% vs 15.24%, p=0.0009; 56.25% vs 18.25%, p=0.0006). Multivariable analysis identified Raynaud’s phenomenon (odds ratio [OR] 8.42, 95% confidence interval [CI] 2.10-33.8, p=0.0026) and elevated neutrophil/lymphocyte ratio (OR 6.92, 95% CI 1.73-27.6, p=0.0061) as independent risk factors for symptomatic cardiac involvement. One patient in the cardiac involved group died of cardiac failure during the observation period.ConclusionAbnormal findings in cardiac examinations and symptomatic cardiac involvement are frequent in patients with IIMs. Evaluating cardiac involvement is important, especially in patients with Raynaud’s phenomenon and elevated neutrophil/lymphocyte ratio at diagnosis.Reference[1]Lilleker JB, Vencovsky J, Wang G, et al. The EuroMyositis registry: an international collaborative tool to facilitate myositis research. Ann Rheum Dis. 2018;77: 30–39.Figure 1.Risk factors for cardiac involvement in inflammatory myopathiesAcknowledgements:NIL.Disclosure of InterestsNone Declared.
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