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1. Engineering chimeric autoantibody receptor T cells for targeted B cell depletion in multiple sclerosis model: An in-vitro study

Author

Maryam Sahlolbei, Mohammadreza Azangou-Khyavy, Javad Khanali, Babak Khorsand, Aref Shiralipour, Naser Ahmadbeigi, Zahra Madjd, Hossein Ghanbarian, Alireza Ardjmand, Seyed Mahmoud Hashemi, and Jafar Kiani

Subjects
Autoreactive B cells, Chimeric autoantibody receptor (CAAR), Experimental autoimmune encephalomyelitis (EAE), Multiple sclerosis (MS), Myelin basic protein (MBP), Science (General), Q1-390, Social sciences (General), H1-99
Abstract

Background: Recent evidence suggests that B cells and autoantibodies have a substantial role in the pathogenesis of Multiple sclerosis. T cells could be engineered to express chimeric autoantibody receptors (CAARs), which have an epitope of autoantigens in their extracellular domain acting as bait for trapping autoreactive B cells. This study aims to assess the function of designed CAAR T cells against B cell clones reactive to the myelin basic protein (MBP) autoantigen. Methods: T cells were transduced to express a CAAR consisting of MBP as the extracellular domain. experimental autoimmune encephalomyelitis (EAE) was induced by injecting MBP into mice. The cytotoxicity, proliferation, and cytokine production of the MBP-CAAR T cells were investigated in co-culture with B cells. Results: MBP-CAAR T cells showed higher cytotoxic activity against autoreactive B cells in all effector-to-target ratios compared to Mock T cell (empty vector-transduced T cell) and Un-T cells (un-transduced T cell). In co-cultures containing CAAR T cells, there was more proliferation and inflammatory cytokine release as compared to Un-T and Mock T cell groups. Conclusion: Based on these findings, CAAR T cells are promising for curing or modulating autoimmunity and can be served as a new approach for clone-specific B cell depletion therapy in multiple sclerosis.

Published
2023
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2. The burden of metabolic risk factors in North Africa and the Middle East, 1990–2019: findings from the Global Burden of Disease StudyResearch in context

Author

Mohammad-Reza Malekpour, Mohsen Abbasi-Kangevari, Seyyed-Hadi Ghamari, Javad Khanali, Mahsa Heidari-Foroozan, Sahar Saeedi Moghaddam, Mohammadreza Azangou-Khyavy, Sahba Rezazadeh-Khadem, Negar Rezaei, Parnian Shobeiri, Zahra Esfahani, Nazila Rezaei, Ali H. Mokdad, Mohsen Naghavi, Bagher Larijani, Farshad Farzadfar, Amirali Aali, Sherief Abd-Elsalam, Meriem Abdoun, Abdorrahim Absalan, Eman Abu-Gharbieh, Niveen ME. Abu-Rmeileh, Ahmed Abu-Zaid, Ali Ahmadi, Sepideh Ahmadi, Ayman Ahmed, Tarik Ahmed Rashid, Marjan Ajami, Mostafa Akbarzadeh-Khiavi, Hanadi Al Hamad, Tariq A. Alalwan, Khalid F. Alhabib, Yousef Alimohamadi, Vahid Alipour, Syed Mohamed Aljunid, Mahmoud A. Alomari, Saleh A. Alqahatni, Rajaa M. Al-Raddadi, Javad Javad Aminian Dehkordi, Mehrdad Amir-Behghadami, Sohrab Amiri, Davood Anvari, Jalal Arabloo, Judie Arulappan, Ashokan Arumugam, Zahra Aryan, Mohammad Athar, Seyyed Shamsadin Athari, Abolfazl Avan, Sina Azadnajafabad, Samad Azari, Hosein Azizi, Nayereh Baghcheghi, Nader Bagheri, Sara Bagherieh, Ovidiu Constantin Baltatu, Akshaya Srikanth Bhagavathula, Vijayalakshmi S. Bhojaraja, Souad Bouaoud, Muhammad Hammad Butt, Luciana Aparecida Campos, Abdulaal Chitheer, Reza Darvishi Cheshmeh Soltani, Aso Mohammad Darwesh, Shirin Djalalinia, Milad Dodangeh, Maysaa El Sayed Zaki, Iffat Elbarazi, Muhammed Elhadi, Waseem El-Huneidi, Rana Ezzeddini, Mohammad Fareed, Hossein Farrokhpour, Ali Fatehizadeh, Yaseen Galali, Amir Ghaderi, Mansour Ghafourifard, Mohammad Ghasemi Nour, Ahmad Ghashghaee, Maryam Gholamalizadeh, Pouya Goleij, Mohamad Golitaleb, Parham Habibzadeh, Nima Hafezi-Nejad, Rabih Halwani, Hamidreza Hasani, Maryam Hashemian, Amr Hassan, Soheil Hassanipour, Hadi Hassankhani, Kamal Hezam, Reza Homayounfar, Seyed Kianoosh Hosseini, Kaveh Hosseini, Mehdi Hosseinzadeh, Soodabeh Hoveidamanesh, Jalil Jaafari, Haitham Jahrami, Elham Jamshidi, Tahereh Javaheri, Sathish Kumar Jayapal, Ali Kabir, Amirali Karimi, Neda Kaydi, Mohammad Keykhaei, Yousef Saleh Khader, Morteza Abdullatif Khafaie, Moien A.B. Khan, Kashif Ullah Khan, Yusra H. Khan, Moawiah Mohammad Khatatbeh, Farzad Kompani, Hamid Reza Koohestani, Mohammed Kuddus, Savita Lasrado, Sang-woong Lee, Soleiman Mahjoub, Ata Mahmoodpoor, Elham Mahmoudi, Elaheh Malakan Rad, Narges Malih, Ahmad Azam Malik, Tauqeer Hussain Mallhi, Yosef Manla, Borhan Mansouri, Mohammad Ali Mansournia, Parham Mardi, Abdoljalal Marjani, Sahar Masoudi, Entezar Mehrabi Nasab, Ritesh G. Menezes, Vildan Mevsim, Yousef Mohammad, Mokhtar Mohammadi, Esmaeil Mohammadi, Noushin Mohammadifard, Arif Mohammed, Sara Momtazmanesh, Fateme Montazeri, Maryam Moradi, Maziar Moradi-Lakeh, Negar Morovatdar, Christopher J.L. Murray, Zuhair S. Natto, Seyed Aria Nejadghaderi, Ali Nowroozi, Morteza Oladnabi, Ahmed Omar Bali, Emad Omer, Hamidreza Pazoki Toroudi, Raffaele Pezzani, Ashkan Pourabhari Langroudi, Sima Rafiei, Mehran Rahimi, Vafa Rahimi-Movaghar, Shayan Rahmani, Amir Masoud Rahmani, Vahid Rahmanian, Chythra R. Rao, Sina Rashedi, Mohammad-Mahdi Rashidi, Reza Rawassizadeh, Elrashdy Moustafa Mohamed Redwan, Malihe Rezaee, Maryam Rezaei, Seyed Mohammad Riahi, Gholamreza Roshandel, Aly Saad, Maha Mohamed Saber-Ayad, Siamak Sabour, Leila Sabzmakan, Basema Saddik, Erfan Sadeghi, Saeid Sadeghian, Amirhossein Sahebkar, Morteza Saki, Saina Salahi, Sarvenaz Salahi, Amir Salek Farrokhi, Marwa Rashad Salem, Hamideh Salimzadeh, Abdallah M. Samy, Nizal Sarrafzadegan, Brijesh Sathian, Melika Shafeghat, Syed Mahboob Shah, Jaffer Shah, Ataollah Shahbandi, Fariba Shahraki-Sanavi, Mehran Shams-Beyranvand, Mohd Shanawaz, Kiomars Sharafi, Javad Sharifi-Rad, Jeevan K. Shetty, Zahra Shokri Varniab, Seyed Afshin Shorofi, Soraya Siabani, Mohammad Sadegh Soltani-Zangbar, Seidamir Pasha Tabaeian, Seyed-Amir Tabatabaeizadeh, Mohammad Tabish, Majid Taheri, Yasaman Taheri Abkenar, Moslem Taheri Soodejani, Amir Taherkhani, Arash Tehrani-Banihashemi, Mohamad-Hani Temsah, Bereket M. Tigabu, Alireza Vakilian, Siavash Vaziri, Bay Vo, Fereshteh Yazdanpanah, Arzu Yigit, Vahit Yiğit, Mazyar Zahir, Burhan Abdullah Zaman, Maryam Zamanian, Moein Zangiabadian, Iman Zare, and Zahra Zareshahrabadi

Subjects
Global burden of disease, Metabolic risk factors, High systolic blood pressure, High fasting plasma glucose, High body-mass index, High-LDL, Medicine (General), R5-920
Abstract

Summary: Background: The objective of this study is to investigate the trends of exposure and burden attributable to the four main metabolic risk factors, including high systolic blood pressure (SBP), high fasting plasma glucose (FPG), high body-mass index (BMI), and high low-density lipoproteins cholesterol (LDL) in North Africa and the Middle East from 1990 to 2019. Methods: The data were retrieved from Global Burden of Disease Study 2019. Summary exposure value (SEV) was used for risk factor exposure. Burden attributable to each risk factor was incorporated in the population attributable fraction to estimate the total attributable deaths and disability-adjusted life-years (DALYs). Findings: While age-standardized death rate (ASDR) attributable to high-LDL and high-SBP decreased by 26.5% (18.6–35.2) and 23.4% (15.9–31.5) over 1990–2019, respectively, high-BMI with 5.1% (−9.0–25.9) and high-FPG with 21.4% (7.0–37.4) change, grew in ASDR. Moreover, age-standardized DALY rate attributed to high-LDL and high-SBP declined by 30.2% (20.9–39.0) and 25.2% (16.8–33.9), respectively. The attributable age-standardized DALY rate of high-BMI with 8.3% (−6.5–28.8) and high-FPG with 27.0% (14.3–40.8) increase, had a growing trend. Age-standardized SEVs of high-FPG, high-BMI, high-SBP, and high-LDL increased by 92.4% (82.8–103.3), 76.0% (58.9–99.3), 10.4% (3.8–18.0), and 5.5% (4.3–7.1), respectively. Interpretation: The burden attributed to high-SBP and high-LDL decreased during the 1990–2019 period in the region, while the attributable burden of high-FPG and high-BMI increased. Alarmingly, exposure to all four risk factors increased in the past three decades. There has been significant heterogeneity among the countries in the region regarding the trends of exposure and attributable burden. Urgent action is required at the individual, community, and national levels in terms of introducing effective strategies for prevention and treatment that account for local and socioeconomic factors. Funding: Bill & Melinda Gates Foundation.

Published
2023
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