Immunologic Basis of Type 2 Biologics for Severe Asthma

Sim Soyoon,Choi Youngwoo,Park Hae-Sim 대한면역학회 2022 Immune Network Vol.22 No.6

Asthma is a chronic airway inflammatory disease characterized by reversible airway obstruction and airway hyperreactivity to various environmental stimuli, leading to recurrent cough, dyspnea, and wheezing episodes. Regarding inflammatory mechanisms, type 2/eosinophilic inflammation along with activated mast cells is the major one; however, diverse mechanisms, including structural cells-derived and non-type 2/neutrophilic inflammations are involved, presenting heterogenous phenotypes. Although most asthmatic patients could be properly controlled by the guided treatment, patients with severe asthma (SA; classified as a treatment-refractory group) suffer from uncontrolled symptoms with frequent asthma exacerbations even on regular anti-inflammatory medications, raising needs for additional controllers, including biologics that target specific molecules found in asthmatic airway, and achieving the precision medicine for asthma. This review summarizes the immunologic basis of airway inflammatory mechanisms and current biologics for SA in order to address unmet needs for future targets.

Micrococcus luteus-derived extracellular vesicles attenuate neutrophilic asthma by regulating miRNAs in airway epithelial cells

Sim Soyoon,Lee Dong-Hyun,Kim Kwang-sun,Park Hyeon Ju,김윤근,Choi Youngwoo,Park Hae-Sim 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Bacterial extracellular vesicles (EVs) have been shown to regulate various pulmonary diseases, but their functions in asthma remain uncertain. To demonstrate the clinical significance of Micrococcus luteus-derived EVs (MlEVs) in asthma, we enrolled 45 asthmatic patients (20 patients with neutrophilic asthma [NA], 25 patients with eosinophilic asthma [EA]) and 40 healthy controls (HCs). When the prevalence of IgG1 and IgG4 specific to MlEVs was evaluated in serum by ELISA, lower levels of MlEV-specific IgG4 (but not IgG1) were noted in asthmatic patients than in HCs. Among asthmatic patients, significantly lower levels of MIEV-specific IgG4 were noted in patients with NA than in those with EA. Moreover, there was a positive correlation between serum MlEV-specific IgG4 levels and FEV1 (%) values. In asthmatic C57BL/6 mice, MlEVs significantly attenuated neutrophilic airway inflammation by reducing the production of IL-1β and IL-17 in bronchoalveolar lavage fluid as well as the number of group 3 innate lymphoid cells (ILC3s) in lung tissues. To clarify the functional mechanism of MlEVs in NA, the effect of MlEVs on airway epithelial cells (AECs) and immune cells was investigated ex vivo. According to microarray analysis, MlEVs upregulated hsa-miR-4517 expression in AECs. Moreover, this miRNA could suppress IL-1β production by monocytes, resulting in the inhibition of ILC3 activation and neutrophil recruitment. These findings suggest that MlEVs could be a novel therapeutic agent for managing unresolved NA by regulating miRNA expression in AECs.

Epithelial Autoantigen-Specific IgG Antibody Enhances Eosinophil Extracellular Trap Formation in Severe Asthma

Lee Dong-Hyun,Jang Jae-Hyuk,Sim Soyoon,최영우,Park Hae-Sim 대한천식알레르기학회 2022 Allergy, Asthma & Immunology Research Vol.14 No.5

Purpose: There have been autoimmune mechanisms for the pathogenesis of severe asthma (SA) involving epithelial autoantigen-specific antibodies. This study aimed to find the function of these antibodies in the formation of eosinophil extracellular traps (EETs), contributing to the development of SA. Methods: Patients with SA (n = 11), those with patients with nonsevere asthma (NSA, n = 41), and healthy controls (HCs, n = 26) were recruited to evaluate levels of epithelial antigens and autoantigen-specific antibodies. Moreover, the significance of epithelial autoantigen-specific antibodies in association with EET production was investigated ex vivo and in vivo. Results: Significantly higher levels of serum cytokeratin (CK) 18 and CK18-specific IgG were observed in patients with SA than in those with NSA (P = 0.001 and P = 0.031, respectively), while no differences were found in serum CK19 or CK19-specific immunoglobulin G (IgG). Moreover, levels of serum CK18 were positively correlated with total eosinophil counts (r = 0.276, P = 0.048) in asthmatics, while a negative correlation was noted between levels of serum CK18 and forced expiratory volume in 1 second (FEV1) %. In the presence of CK18-specific IgG, peripheral eosinophils from asthmatics released EETs, which further increased CK18 production from airway epithelial cells. In severe asthmatic mice, CK18 expression and CK18-specific IgG production were enhanced in the lungs, where EET treatment enhanced CK18 expression and CK18-specific IgG production, either of which was not suppressed by dexamethasone. Conclusions: These suggest that EETs could enhance epithelial autoantigen (CK18)-induced autoimmune responses, further stimulating EET production and type 2 airway responses, which is a new therapeutic target for SA.

Ultrasound-guided erector spinae plane block for pain management after gastrectomy: a randomized, single-blinded, controlled trial

Heejoon Jeong,Ji Won Choi,Woo Seog Sim,Duk Kyung Kim,Yu Jeong Bang,Soyoon Park,Hyean Yeo,Hara Kim 대한통증학회 2022 The Korean Journal of Pain Vol.35 No.3

Background: Open gastrectomy causes severe postoperative pain. Therefore, we investigated the opioid-sparing effect of the ultrasound-guided bilateral erector spinae plane block (ESPB) after open gastrectomy. Methods: Adult patients undergoing open gastrectomy were randomly assigned to either the ESPB group (ESPB + fentanyl based intravenous patient-controlled analgesia [IV-PCA]) or a control group (fentanyl based IV-PCA only). The primary outcome was total fentanyl equivalent consumption during the first 24 hour postoperatively. Secondary outcomes were pain intensities using a numeric rating scale at the postanesthesia care unit (PACU) and at 3, 6, 12, and 24 hour postoperatively, and the amount of fentanyl equivalent consumption during the PACU stay and at 3, 6, and 12 hour postoperatively, and the time to the first request for rescue analgesia. Results: Fifty-eight patients were included in the analysis. There was no significant difference in total fentanyl equivalent consumption during the first 24 hour postoperatively between the two groups (P = 0.471). Pain intensities were not significantly different between the groups except during the PACU stay and 3 hour postoperatively (P < 0.001, for both). Time to the first rescue analgesia in the ward was longer in the ESPB group than the control group (P = 0.045). Conclusions: Ultrasound-guided ESPB did not decrease total fentanyl equivalent consumption during the first 24 hour after open gastrectomy. It only reduced postoperative pain intensity until 3 hour postoperatively compared with the control group. Ultrasound-guided single-shot ESPB cannot provide an efficient opioid-sparing effect after open gastrectomy.

Cross-protective efficacy of the O1 Manisa + O 3039 bivalent vaccine and the O 3039 monovalent vaccine against heterologous challenge with FMDV O/Jincheon/SKR/2014 in pig

Kim, Taeseong,Hong, Jang-Kwan,Oem, Jae-Ku,Lee, Kwang-Nyeong,Lee, Hyang-Sim,Kim, Yong Joo,Ryoo, Soyoon,Ko, Young-Joon,Park, Jong-Hyeon,Choi, Jida,Lee, Seung Heon,Jo, Hye Jun,Lee, Myoung-Heon,Kim, Byoun Elsevier 2019 Vaccine Vol.37 No.12

<P><B>Abstract</B></P> <P>After massive foot-and-mouth disease (FMD) outbreaks originated from Jincheon County from Dec. 2014 to Apr. 2015, the effectiveness of the previous FMD vaccine containing only the O1 Manisa as the O antigen, O1 Manisa + A Malaysia 97 + Asia 1 Sharmir trivalent vaccine, was questioned in South Korea, and a change in the O antigen in FMD vaccines was demanded to control the FMD caused by FMDV O/Jincheon/SKR/2014, the O Jincheon strain. Therefore, the efficacies of O1 Manisa + O 3039 bivalent vaccine and O 3039 monovalent vaccine were studied for cross-protection against heterologous challenge with the O Jincheon strain. In this study, the efficacy of the O1 Manisa + O 3039 bivalent vaccine was better than that of the O 3039 monovalent vaccine, even though the serological relationship (r<SUB>1</SUB> value) between O Jincheon and O 3039 was matched according to the OIE Terrestrial Manual. According to serological test results from vaccinated specific pathogen free pigs, virus neutralization test titers against Jincheon were good estimates for predicting protection against challenge. A field trial of the O1 Manisa + O 3039 bivalent vaccine was performed to estimate the possibility of field application in conventional pig farms, especially due to concerns about the effect of maternally derived antibodies (MDA) in field application of the FMD vaccine. According to the result of the field trial, the O1 Manisa + O 3039 bivalent vaccine was considered to overcome MDA. The results of the efficacy and field trials indicated that the O1 Manisa + O3039 vaccine could be suitable to replace previous FMD vaccines to control the FMD field situation caused by O Jincheon FMDV.</P>