Article
Immunology
Ana Karen Penafiel Vicuna, Marco Yamazaki Nakashimada, Ximena Leon Lara, Elizabeth Mendieta Flores, Maria Enriqueta Nunez Nunez, Juan Carlos Lona-Reyes, Leticia Hernandez Nieto, Maria Guadalupe Ramirez Vazquez, Joel Barroso Santos, Alvaro Lopez Iniguez, Yolanda Gonzalez, Martha Torres, Jose Luis Lezana Fernandez, Carla M. Roman Montes, Edgar Alejandro Medina-Torres, Edith Gonzalez Serrano, Juan Carlos Bustamante Ogando, Saul Lugo Reyes, Oscar Zavaleta Martinez, Aide Tamara Staines Boone, Edna Venegas Montoya, Nancy Evelyn Aguilar Gomez, Camille Soudee, Emmanuelle Jouanguy, Anne Puel, Stephanie Boisson-Dupuis, Sigifredo Pedraza Sanchez, Jean-Laurent Casanova, Francisco Espinosa Rosales, Sara Espinosa Padilla, Jacinta Bustamante, Lizbeth Blancas Galicia
Summary: This study reviewed the clinical, immunological, and genetic characteristics of MSMD patients in Mexico and identified IL12RB1 gene defect as the main cause of MSMD in the cohort. BCG infection was found to be the primary cause of morbidity and mortality in these patients.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Abderrahmane Errami, Jamila El Baghdadi, Fatima Ailal, Ibtihal Benhsaien, Jalila El Bakkouri, Leila Jeddane, Noureddine Rada, Noufissa Benajiba, Khaoula Mokhantar, Kaoutar Ouazahrou, Sanae Zaidi, Laurent Abel, Jean-Laurent Casanova, Stephanie Boisson-Dupuis, Jacinta Bustamante, Ahmed Aziz Bousfiha
Summary: We studied the genetic predisposition to mycobacterial diseases in Moroccan kindreds through clinical, immunological, and genetic analysis. The study revealed a Mendelian susceptibility to mycobacterial disease (MSMD) in these families, leading to severe tuberculosis and complications of BCG vaccination. Systematic genetic studies are necessary in the presence of these infections, and BCG vaccination should be delayed in newborn siblings until a genetic predisposition to mycobacteria is excluded.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Zhenxing Liu, Mi Zhou, Chao Yuan, Zhengyi Ni, Wenqiang Liu, Yang Tan, Dazhi Zhang, Xiaopei Zhou, Tingting Zou, Jiarui Wang, Meiqi Hou, Xuejie Peng, Xianqin Zhang
Summary: This study investigated the pathogenic genes and molecular mechanisms of Mendelian susceptibility to mycobacterial disease (MSMD) patients. Two novel mutations in the STAT1 gene were identified, which affected the binding ability of STAT1 protein to target DNA and the translocation of STAT1 protein into the nucleus, leading to the occurrence of MSMD.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Immunology
Frederik Staels, Flaminia Lorenzetti, Kerstin De Keukeleere, Mathijs Willemsen, Margaux Gerbaux, Julika Neumann, Thomas Tousseyn, Emanuela Pasciuto, Paul De Munter, Xavier Bossuyt, Rik Gijsbers, Adrian Liston, Stephanie Humblet-Baron, Rik Schrijvers
Summary: In this study, we identified and characterized a homozygous stop mutation in IL23R, which resulted in impaired IL-23 immunity and correlated with disseminated non-tuberculous mycobacterial disease in an adult patient. This finding further supports the importance of IL-23 in IL-17-mediated antifungal immunity.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Clinical Neurology
Zahra Aghelan, Saeed Karima, Seyed Hosein Abtahi, Habibolah Khazaie, Yahya Salimi, Reza Khodarahmi
Summary: A growing body of literature suggests that cytokines can play an important role in chronic insomnia disorder (CID). This study found that levels of proinflammatory mediators, including IL-12, IFN-gamma, and ICAM-1, were elevated in CID patients compared to healthy controls. The duration of REM sleep was also found to decrease with increased concentrations of IL-12 and IFN-gamma. Additionally, a lower serum concentration of IL-1ra was negatively correlated with the severity of insomnia in CID patients. These findings indicate that an imbalance of proinflammatory mediators and anti-inflammatory cytokines is important in the pathogenesis of CID.
Article
Dermatology
Karolina Dolezalova, Tomas Strachan, Radoslav Matej, Dita Ricna, Marketa Bloomfield
Summary: This study presents a case series of four pediatric patients with Mendelian susceptibility to mycobacterial diseases (MSMD), specifically with IFN gamma R1 and STAT1 deficiencies, and cutaneous non-tuberculous mycobacteria (NTM)/bacillus Calmette-Guerin (BCG) infections. The results highlight the importance of considering MSMD in patients with seemingly normal immune function who present with NTM/BCG infections, as timely diagnosis and treatment can significantly improve disease outcomes.
EUROPEAN JOURNAL OF DERMATOLOGY
(2022)
Letter
Dermatology
Aika Shionoya, Yuko Yoto, Tokimasa Hida, Aki Ishikawa, Tadashi Hasegawa, Takeshi Tsugawa, Hisashi Uhara
Summary: In this article, we present a case of lupus vulgaris caused by BCG vaccination in a patient with Mendelian susceptibility to mycobacterial disease (MSMD) due to a novel STAT1 gene variation. Dermatologists should consider MSMD as a possible diagnosis in patients who develop cutaneous tuberculosis after BCG vaccination. This helps to ensure proper vaccination in individuals with inborn errors of immunity.
BRITISH JOURNAL OF DERMATOLOGY
(2023)
Review
Immunology
Stephanie Boisson-Dupuis, Jacinta Bustamante
Summary: Clinical diseases caused by Mycobacterium tuberculosis, BCG vaccines, and environmental mycobacteria can result from inborn errors of immunity (IEIs). These IEIs are associated with impairments in the development and/or function of cells involved in host defense. Vulnerability to mycobacterial diseases is associated with IFN-gamma deficiency, with different levels of deficiency leading to different susceptibilities to mycobacteria.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Article
Dentistry, Oral Surgery & Medicine
Mabelle Freitas Monteiro, Marcio Zaffalon Casati, Enilson Antonio Sallum, Karina Gonzales Silverio, Francisco Humberto Nociti-Jr, Renato Correa Viana Casarin
Summary: This study found that aggressive periodontitis (GAgP) patients and their children have a different local inflammatory response compared to healthy controls, and there is a familial aggregation. The cytokine profile and subgingival response imbalance characterized by decreased IFN-gamma/IL-4 and IL-10/IL-1 beta ratios were observed in both GAgP patients and their children.
Article
Medicine, Research & Experimental
Claudia Augusta Di Trani, Assunta Cirella, Leire Arrizabalaga, Maite Alvarez, Angela Bella, Myriam Fernandez-Sendin, Joan Salvador Russo-Cabrera, Celia Gomar, Nuria Ardaiz, Alvaro Teijeira, Elixabet Bolanos, Jose Gonzalez-Gomariz, Itziar Otano, Fernando Aranda, Belen Palencia, Aina Segues, Shuyu Huang, Sander M. J. van Duijnhoven, Andrea van Elsas, Ignacio Melero, Pedro Berraondo
Summary: This study aims to improve the efficacy of cancer immunotherapy by enhancing the tethering of IL-12 to tumor cells. The fusion of IL-12 with diabodies successfully achieved binding to tumor cells and reduced its systemic availability. This strategy could potentially enhance the therapeutic effects and minimize the toxicity of IL-12 in cancer treatment.
MOLECULAR THERAPY NUCLEIC ACIDS
(2023)
Article
Immunology
Rintaro Ono, Miyuki Tsumura, Saho Shima, Yusuke Matsuda, Kenji Gotoh, Yurina Miyata, Yuko Yoto, Dan Tomomasa, Takanori Utsumi, Hidenori Ohnishi, Zenichiro Kato, Naruhiko Ishiwada, Aki Ishikawa, Taizo Wada, Hisashi Uhara, Ryuta Nishikomori, Daisuke Hasegawa, Satoshi Okada, Hirokazu Kanegane
Summary: This study identified eight cases of Mendelian susceptibility to mycobacterial disease (MSMD) associated with heterozygous dominant-negative (DN) variants in the STAT1 gene in four Japanese families. Functional analysis confirmed that these variants result in loss-of-function and have a dominant negative effect on wild-type STAT1. The findings suggest that autosomal dominant STAT1 deficiency may be prevalent in Japanese patients with BCG-related MSMD.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Nesrine Radwan, Zohreh Nademi, Su Han Lum, Terry Flood, Mario Abinun, Stephen Owens, Eleri Williams, Andrew R. Gennery, Sophie Hambleton, Mary A. Slatter
Summary: This retrospective survey found that HSCT can be a successful treatment for patients with mycobacterial susceptibility, even with disseminated infection and in the absence of an HLA matched donor.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Ansia van Coller, Brigitte Glanzmann, Helena Cornelissen, Marlo Moller, Craig Kinnear, Monika Esser, Richard Glashoff
Summary: This study successfully assessed the integrity of the IL-12-IFN-gamma cytokine pathways in patients with MSMD-like phenotypes using a set of functional assays. The importance of investigating PID and TB susceptibility in TB endemic regions such as South Africa was highlighted, emphasizing the need for in vitro functional investigations to better understand immune function. Regular application of functional assays to patients suspected of PID related to mycobacterial susceptibility was recommended to pave the way for targeted treatment and improved disease management.
Review
Infectious Diseases
Kosuke Noma, Yoko Mizoguchi, Miyuki Tsumura, Satoshi Okada
Summary: Mendelian susceptibility to mycobacterial disease (MSMD) is a genetic disorder characterized by impaired IFN-gamma immunity predisposing individuals to infections by intracellular pathogens. Recent discoveries have introduced three new genetic disorders in the context of MSMD, namely AR IFN-gamma, T-bet, and ZNFX1 deficiencies. Multifocal osteomyelitis is a prominent symptom in MSMD patients with impaired IFN-gamma responses. Further research is needed to elucidate the genetic etiologies and pathogenesis of MSMD cases.
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Article
Medicine, Research & Experimental
Yaoju Tan, Yunhong Tan, Junlian Li, Pengnan Hu, Ping Guan, Haobin Kuang, Qide Liang, Yanyan Yu, Zhongnan Chen, Quan Wang, Zhenping Yang, DiLiNaZi AiKeReMu, Yu Pang, Jianxiong Liu
Summary: The study developed a new immunological method using IFN-gamma and IL-2 combinations to differentiate active TB from other pulmonary diseases, showing potential for accurate diagnosis. The sensitivity of series combination test was higher, while the specificity of parallel combination of IFN-gamma /IL-2 was increased. The diagnostic accuracy of series combination correlated with disease severity.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Public, Environmental & Occupational Health
M. P. Salcedo, R. Gowen, A. M. Rodriguez, S. Fisher-Hoch, M. Daheri, L. Guerra, P. A. Toscano, M. Gasca, J. Morales, F. E. Reyna-Rodriguez, B. Cavazos, E. Marin, C. Perez, M. Guerra, A. Milbourne, M. L. Varon, B. Reininger, M. E. Fernandez, T. Ogburn, P. E. Castle, J. McCormick, E. Baker, E. Hawk, K. M. Schmeler
Summary: By implementing a comprehensive intervention program, including community education, patient navigation, and training for local providers, a large number of women in the Rio Grande Valley were able to receive diagnosis and treatment for cervical dysplasia. If sustained, these efforts are expected to decrease cervical cancer rates in the region.
PERSPECTIVES IN PUBLIC HEALTH
(2023)
Article
Allergy
Xiao Chang, Michael March, Frank Mentch, Huiqi Qu, Yichuan Liu, Joseph Glessner, Patrick Sleiman, Hakon Hakonarson
Summary: This study aimed to identify genetic loci associated with asthma in African American individuals. Through a meta-analysis of three cohorts, 12 genetic loci were found to be significantly associated with asthma. These loci may serve as candidate genetic loci for therapeutic target identification in African populations.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Hui-Qi Qu, Charlly Kao, James Garifallou, Fengxiang Wang, James Snyder, Diana J. Slater, Cuiping Hou, Michael March, John J. Connolly, Joseph T. Glessner, Hakon Hakonarson
Summary: This study investigated the impact of varying time periods from blood draw to PBMC isolation on the subsequent transcriptome profiling of different cell types in PBMCs using single cell RNA-seq. The results showed significant changes in the transcriptome expression of various cell types over time, highlighting the importance of considering this factor in interpreting experimental results.
Article
Immunology
Christopher J. Cardinale, Xiao Chang, Zhi Wei, Hui-Qi Qu, Jonathan P. Bradfield, Constantin Polychronakos, Hakon Hakonarson
Summary: This study conducted a genome-wide association study (GWAS) to identify genetic correlates of the age of onset in type 1 diabetes. The study found associations between the HLA-DQB1 gene and age of diagnosis, as well as the variant rs10833518 in the NELL1 gene on chromosome 11. The study also implicated the HTATIP2 gene in T cell regulation and its role in the development of type 1 diabetes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Alanna Strong, Hui-Qi Qu, Sinead Cullina, Morgan L. McManus, Elaine H. Zackai, Joseph Glessner, Eimear E. Kenny, Hakon Hakonarson
Summary: Joubert syndrome (JBTS) is a genetic disorder characterized by primary cilium dysfunction, leading to hypotonia, developmental delay, and a specific cerebellar malformation. Although many causal genes have been identified, a significant proportion of individuals with clinical symptoms cannot be molecularly diagnosed.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Arthur M. Feldman, Edward K. Kasper, Hui-Qi Qu
JACC-HEART FAILURE
(2023)
Article
Genetics & Heredity
Wentao Zhou, Jun Jia, Hui-Qi Qu, Feier Ma, Junyi Li, Xiaohui Qi, Xinyi Meng, Zhiyong Ding, Gang Zheng, Hakon Hakonarson, Xiantie Zeng, Jin Li, Qianghua Xia
Summary: In this study, a genetic analysis was conducted on the structural variants underlying familial hallux valgus using whole exome sequencing approach. A total of 372 copy number variations were found, with 43 being present only in cases and not in controls or healthy individuals. These copy number variations were enriched in gene sets related to immune signaling pathway and cytochrome P450 metabolism. The study suggests that hallux valgus is a degenerative joint disease involving dysregulation of immune and metabolism signaling pathways.
FRONTIERS IN GENETICS
(2023)
Review
Cell Biology
Caitlyn M. Brenner, Muaaz Choudhary, Michael G. McCormick, David Cheung, Gavin P. Landesberg, Ju-Fang Wang, Jianliang Song, Thomas G. Martin, Joseph Y. Cheung, Hui-Qi Qu, Hakon Hakonarson, Arthur M. Feldman
Summary: BAG3 is a versatile protein found in animals and plants, with prominent expression in certain tissues and cancers. It plays multiple roles, including supporting autophagy, inhibiting apoptosis, maintaining mitochondrial homeostasis, and facilitating excitation-contraction coupling. High levels of BAG3 are associated with chemotherapy resistance in cancer cells, while loss or gain of function variants are linked to cardiomyopathy.
Article
Oncology
Hui-Qi Qu, John J. Connolly, Peter Kraft, Jirong Long, Alexandre Pereira, Christopher Flatley, Constance Turman, Bram Prins, Frank Mentch, Paulo A. Lotufo, Per Magnus, Meir J. Stampfer, Rulla Tamimi, A. Heather Eliassen, Wei Zheng, Gun Peggy Stromstad Knudsen, Oyvind S. Helgeland, Adam Butterworth, Hakon M. Hakonarson, Patrick Sleiman
Summary: Through the collaboration model of IHCC, a globally applicable trans-ethnic PRS for BMI was developed, which can effectively estimate an individual's risk of developing complex traits such as obesity.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Medicine, Research & Experimental
Susan P. Fisher-Hoch, Jennifer E. Below, Kari E. North, Joseph B. McCormick
Summary: Minority populations have been underrepresented in clinical research trials, leading to increasing burdens of cancer and chronic disease. Challenges to recruiting minorities in the United States include issues of trust. Successful recruitment strategies involve addressing community concerns and training staff from the same community. In one case study, a team was recruited and trained from a local community in Texas, enrolling over five thousand Mexican Americans in a cohort study on chronic diseases and acquiring advanced skills and health information.
JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Clinical Neurology
Patrick M. Sleiman, Hui-Qi Qu, John J. Connolly, Frank Mentch, Alexandre Pereira, Paulo A. Lotufo, Stephen Tollman, Ananyo Choudhury, Michele Ramsay, Norihiro Kato, Kouichi Ozaki, Risa Mitsumori, Jae-Pil Jeon, Chang Hyung Hong, Sang Joon Son, Hyun Woong Roh, Dong-gi Lee, Naaheed Mukadam, Isabelle F. Foote, Charles R. Marshall, Adam Butterworth, Bram P. Prins, Joseph T. Glessner, Hakon Hakonarson
Summary: The aim of this study was to develop a trans-ethnic genomic informed risk assessment (GIRA) algorithm for Alzheimer's disease (AD) through collaboration between IHCC and DAC. The GIRA model included polygenic risk score, apolipoprotein E haplotypes, and non-genetic covariates. The performance of the GIRA model was validated in different populations and proteins related to female infertility and autoimmune thyroiditis were identified. This study provides a potential tool for identifying high-risk individuals for future clinical applications.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biochemistry & Molecular Biology
Yichuan Liu, Hui-Qi Qu, Xiao Chang, Frank D. Mentch, Haijun Qiu, Xiang Wang, Amir Hossein Saeidian, Deborah Watson, Joseph Glessner, Hakon Hakonarson
Summary: Children with birth defects often have distinct clinical features and are predisposed to developing cancer. We performed a whole genome sequencing study and identified recurrent genetic variants associated with cancer development in these children. These variants were found in protein-coding and non-coding regions of the genome, including exons, introns, and ncRNAs.
Letter
Oncology
Yichuan Liu, Hui-Qi Qu, Xiao Chang, Frank D. Mentch, Haijun Qiu, Kenny Nguyen, Xiang Wang, Amir Hossein Saeidian, Deborah Watson, Joseph Glessner, Hakon Hakonarson
CANCER COMMUNICATIONS
(2023)
Meeting Abstract
Peripheral Vascular Disease
Anna Felicja Dominiczak
JOURNAL OF HYPERTENSION
(2023)
Review
Cell & Tissue Engineering
Hui-Qi Qu, Charlly Kao, Hakon Hakonarson
Summary: Single-cell RNA sequencing (scRNA-seq) is a revolutionary technology that has greatly contributed to our understanding of cellular heterogeneity and gene expression dynamics, particularly in stem cell research. Different types of scRNA-seq technologies have been developed and they offer distinct advantages in capturing cellular heterogeneity and characterizing rare cell populations within complex tissues.
