Author: "Erin M. Wilfong" - Searchworks@Jio Institute Digital Library Search Results

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1. Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine

Author: Kevin J. Kramer, Erin M. Wilfong, Kelsey Voss, Sierra M. Barone, Andrea R. Shiakolas, Nagarajan Raju, Caroline E. Roe, Naveenchandra Suryadevara, Lauren M. Walker, Steven C. Wall, Ariana Paulo, Samuel Schaefer, Debolanle Dahunsi, Camille S. Westlake, James E. Crowe, Robert H. Carnahan, Jeffrey C. Rathmell, Rachel H. Bonami, Ivelin S. Georgiev, and Jonathan M. Irish
Subjects: Science
Abstract: Vaccination against COVID-19 has shown activation of different immune cell types. Here the authors characterise the immune response to the SARS-CoV-2 mRNA vaccine using longitudinal CyTOF single cell approaches to characterise antigen specific B and T-cell responses promoted by this vaccine.
Published: 2022
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2. Jo-1 autoantigen-specific B cells are skewed towards distinct functional B cell subsets in anti-synthetase syndrome patients

Author: Jennifer Young-Glazer, Alberto Cisneros, Erin M. Wilfong, Scott A. Smith, Leslie J. Crofford, and Rachel H. Bonami
Subjects: Autoimmune diseases, B lymphocytes, Autoimmunity, Myositis, Diseases of the musculoskeletal system, RC925-935
Abstract: Abstract Background Anti-Jo-1 autoantibodies which recognize histidyl-tRNA synthetase identify patients with the rare rheumatologic disease, anti-histidyl-tRNA synthetase syndrome (Jo-1 ARS), a phenotypically distinct subset of idiopathic inflammatory myopathies (IIM). Jo-1-binding B cells (JBCs) are implicated in disease pathogenesis, yet they have not been studied directly. We therefore aimed to characterize JBCs to better understand how they expand and function in Jo-1 ARS. Methods We enrolled 10 IIM patients diagnosed with Jo-1 ARS, 4 patients with non-Jo-1 IIM, and 8 age- and sex-matched healthy controls. We phenotypically characterized peripheral blood mononuclear cells (PBMCs) ex vivo using flow cytometry to define the B cell subsets in which JBCs reside. We further tested their ability to differentiate into antibody-secreting cells following stimulation in vitro. Results The majority of JBCs were IgM+ (not class-switched). Compared to non-JBCs in the same donors, JBCs contained a higher percentage of autoimmune-prone CD21lo cells and were increased in the CD21lo IgM+ IgD− CD27+ memory subset relative to healthy donor B cells. Whereas non-JBCs were present in the anergic BND B cell subset, JBCs were nearly absent from this compartment. JBCs were detected among plasmablasts in some donors, but a reduced frequency of JBCs differentiated into CD38hi24− plasmablasts compared to non-JBCs present in the same wells following in vitro stimulation. Conclusions JBCs are enriched for autoimmune-prone CD21lo B cells, some of which exhibit a memory phenotype in the peripheral repertoire of Jo-1 ARS patients. JBCs undergo limited class switch and show reduced capacity to differentiate into antibody-secreting cells. This suggests complex B cell biology exists beyond class-switched cells that differentiate to secrete anti-Jo-1 autoantibody (i.e., what is captured through serum autoantibody studies). New Jo-1 ARS therapies should thus ideally target non-class-switched JBCs in addition to those that have undergone IgG class-switching to most effectively block cross-talk with autoreactive T cells.
Published: 2021
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3. Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic

Author: Anna M. Cervantes-Arslanian, MD, Chakradhar Venkata, MD, Pria Anand, MD, Joseph D. Burns, MD, Charlene J. Ong, MD, Allison M. LeMahieu, MS, Phillip J. Schulte, PhD, Tarun D. Singh, MD, Alejandro A. Rabinstein, MD, Neha Deo, BS, Vikas Bansal, MBBS, MPH, Karen Boman, BS, Juan Pablo Domecq Garces, MD, Donna Lee Armaignac, PhD, APRN, Amy B. Christie, MD, Roman R. Melamed, MD, Yasir Tarabichi, MD, MSCR, Sreekanth R. Cheruku, MD, MPH, Ashish K. Khanna, MD, FCCP, FCCM, FASA, Joshua L. Denson, MD, MS, Valerie M. Banner-Goodspeed, MPH, Harry L. Anderson, III, MD, FACS, FICS, FCCM, FCCP, FAIM, Ognjen Gajic, MD, MS, Vishakha K. Kumar, MD, MBA, Allan Walkey, MD, Rahul Kashyap, MD, MBA, on behalf of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Philippe Clevenbergh, Rolando Claure-Del Granado, Jose A. Mercado, Esdenka Vega-Terrazas, Maria F. Iturricha-Caceres, Ruben Garza, Eric Chu, Victoria Chan, Oscar Y Gavidia, Felipe Pachon, Yeimy A Sanchez, Danijel knežević, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Dimitrios Kantas, Vasileios Koulouras, Estela Pineda, Gabina María Reyes Guillen, Helin Archaga Soto, Ana Karen Vallecillo Lizardo, Csaba Kopitkó, Ágnes Bencze, István Méhész, Zsófia Gerendai,, Girish Vadgaonkar, Rekha Ediga, Shilpa Basety, Shwetha Dammareddy, Phani Sreeharsha Kasumalla, Smitha S. Segu, Tuhin Chakraborty, Epcebha Joyce, Sridhar Papani, Mahesh Kamuram, Mradul Kumar Daga, Munisha Agarwal, Ishan Rohtagi, Anusha Cherian, Sreejith Parameswaran, Magesh Parthiban, Phaneendra Doddaga, Neethi Chandra, Puneet Rijhwani, Ashish Jain, Aviral Gupta, Ram Mohan Jaiswal, Ambika Tyagi, Nimish Mathur, Madhav Prabhu, Vishal Jakati, Mukur Petrolwala, Bharat Ladva, Surapaneni Krishna Mohan, Ekambaram Jyothisree, Umamaheswara Raju, Janaki Manduva, Naresh Kolakani, Shreeja Sripathi, Sheetal Chaitanya, Kamlesh Kumar Agrawal, Vijendra Baghel, Kirti Kumar Patel, Nooshin Dalili, Mohsen Nafa, Wataru Matsuda, Reina Suzuki, Michihito Kyo, Shu Tahara, Mineji Hayakawa, Kunihiko Maekawa, Masamitsu Sanui, Sho Horikita, Yuki Itagaki, Akira Kodate, Yuki Takahashi, Koyo Moriki, Takuya Shiga, Yudai Iwasaki, Hidenobu Shigemitsu, Yuka Mishima, Nobuyuki Nosaka, Michio Nagashima, Abdulrahman Al-Fares, Rene Rodriguez-Gutierrez, Jose Gerardo Gonzalez-Gonzalez, Alejandro Salcido-Montenegro, Adrian Camacho-Ortiz, Mariana Janeth Hermosillo Ulloa, Fatimah Hassan-Hanga, Hadiza Galadanci, Abubakar Shehu Gezawa, Halima M. S. Kabara, Taiwo Gboluwaga Amole, Halima Kabir, Dalha Gwarzo Haliru, Abdullahi S Ibrahim, Muhammad Sohaib Asghar, Mashaal Syed, Syed Anosh Ali Naqvi, Igor Borisovich Zabolotskikh,, Konstantin Dmitrievich Zybin, Sergey Vasilevich Sinkov, Tatiana Sergeevna Musaeva, Razan K Alamoudi, Hassan M. AlSharif, Sarah A. Almazwaghi, Mohammed S Elsakran, Mohamed A Aid, Mouaz A Darwich, Omnia M Hagag, Salah A Ali, Alona rocacorba, Kathrine Supeña, Efren Ray Juane, Jenalyn Medina, Jowany Baduria, Marwa Ridha Amer, Mohammed Abdullah, Bawazeer, Talal I. Dahhan, Eiad Kseibi, Abid Shahzad Butt, Syed Moazzum Khurshid, Muath Rabee, Mohammed Abujazar, Razan Alghunaim, Maal Abualkhair, Abeer Turki AlFirm, Yaseen M Arabi, Sheryl Ann Abdukahil, Mohammed A Almazyad, Mohammed I Alarifi, Jara M Macarambon, Ahmad Abdullah Bukhari, Hussain A. Albahrani, Kazi N Asfina, Kaltham M Aldossary, Marija Zdravkovic, Zoran Todorovic, Viseslav Popadic, Slobodan Klasnja, Ana Andrijevic, Srdjan Gavrilovic, Vladimir Carapic, Bojan Kovacevic, Jovana Bojicic, Stevanovic Predrag, Dejan S Stojakov, Duska K Ignjatovic, Suzana C Bojic, Marina M Bobos, Irina B Nenadic, Milica S Zaric, Marko D Djuric, Vladimir R Djukic, Santiago Y. Teruel, Belen C. Martin, Uluhan Sili, Huseyin Bilgin, Pinar Ay, Varsha P Gharpure, Usman Raheemi, Kenneth W. Dodd, Nicholas Goodmanson, Kathleen Hesse, Paige Bird, Chauncey Weinert, Nathan Schoenrade, Abdulrahman Altaher, Esmael Mayar, Matthew Aronson, Tyler Cooper, Monica Logan, Brianna Miner, Gisele Papo, Eric M. Siegal, Phyllis Runningen, Suzanne Barry, Christopher Woll, Gregory Wu, Erin Carrole, Kathryn Burke, Mustafa Mohammed, Roman R. Melamed, David M. Tierney, Love A. Patel, Vino S. Raj, Barite U. Dawud, Narayana Mazumder, Abbey Sidebottom, Alena M. Guenther, Benjamin D. Krehbiel, Nova J. Schmitz, Stacy L. Jepsen, Lynn Sipsey, Anna Schulte, Whitney Wunderlich, Cecely Hoyt, Abhijit A Raval, Andrea Franks, Katherine Irby, Ronald C. Sanders, Jr., Glenda Hefley, Jennifer M. Jarvis, Anmol Kharbanda, Sunil Jhajhria, Zachary Fyffe, Stephen Capizzi, Bethany Alicie, Martha Green, Lori Crockarell, Amelia Drennan, Kathleen Dubuque, Tonya Fambrough, Nikole Gasaway, Briana Krantz, Peiman Nebi, Jan Orga, Margaret Serfass, Alina Simion, Kimberly Warren, Cassie Wheeler, CJ Woolman, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Andrew S. Moyer, George M. Verghese, Andrea Sikora Newsome, Christy C. Forehand, Rebecca Bruning, Timothy W. Jones, Moldovan Sabov, Fatema Zaidi, Fiona Tissavirasingham, Dhatri Malipeddi, Jarrod M Mosier, Karen Lutrick, Beth Salvagio Campbell, Cathleen Wilson, Patrick Rivers, Jonathan Brinks, Mokenge Ndiva Mongoh, Boris Gilson, Donna Lee Armaignac, Don Parris, Maria Pilar Zuniga, Ilea Vargas, Viviana Boronat, Anneka Hutton, Navneet Kaur, Prashank Neupane, Nohemi Sadule-Rios, Lourdes M. Rojas, Aashish Neupane, Priscilla Rivera, Carlos Valle Carlos, Gregory Vincent, Mahesh Amin, Mary E Schelle, Amanda Steadham, Christopher M Howard, Cameron McBride, Jocelyn Abraham, Orlando Garner, Katherine Richards, Keegan Collins, Preethi Antony, Sindhu Mathew, Valerie C. Danesh, Gueorgui Dubrocq, Amber L. Davis, Marissa J Hammers, ill M. McGahey, Amanda C. Farris, Elisa Priest, Robyn Korsmo, Lorie Fares, Kathy Skiles, Susan M. Shor, Kenya Burns, Corrie A Dowell, Gabriela “Hope” Gonzales, Melody Flores, Lindsay Newman, Debora A Wilk, Jason Ettlinger, Jaccallene Bomar, Himani Darji, Alejandro Arroliga, Alejandro C Arroliga, Corrie A. Dowell, Gabriela Hope Conzales, Debora A. Wilk, Paras B. Khandhar, Elizabeth Kring, Valerie M. Banner-Goodspeed, Somnath Bose, Lauren E. Kelly, Melisa Joseph, Marie McGourty, Krystal Capers, Benjamin Hoenig, Maria C. Karamourtopoulos, Anica C. Law, Elias N. Baedorf Kassis, Allan J. Walkey, Sushrut S. Waikar, Michael A. Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Maj Andrew M. Hersh, CPT Stephanie L Wachs, Brittany S. Swigger, Stephanie L Wachs, Capt Lauren A. Sattler, Capt Michael N. Moulton, Kimberly Zammit, Patrick, J McGrath, William Loeffler, Maya, R. Chilbert, Aaron S. Miller, Edwin L. Anderson, Rosemary Nagy, Ravali R. Inja, Pooja A. Nawathe, Isabel Pedraza, Jennifer Tsing, Karen Carr, Anila Chaudhary, Kathleen Guglielmino, Raghavendra Tirupathi, Alymer Tang, Arshad Safi, Cindy Green, Jackie Newell, Rayan E. Ihle, Shelda A. Martin, Elaine A. Davis, Katja M. Gist, Imran A Sayed, John Brinton, Larisa Strom, Kathleen Chiotos, Allison M. Blatz, Giyoung Lee, Ryan H. Burnett, Guy I. Sydney, Danielle M. Traynor, Karissa Nauert, Annika Gonzalez, Mariel Bagley, Anita Santpurkar, Salim Surani, Joshua White, Aftab Khan, Rahul Dhahwal, Sreekanth Cheruku, Farzin Ahmed, Christopher Deonarine, Ashley Jones, Mohammad-Ali Shaikh, David Preston, Jeanette Chin, Vidula Vachharajani, Abhijit Duggal, Prabalini Rajendram, Omar Mehkri, Siddharth Dugar, Michelle Biehl, Gretchen Sacha, Stuart Houltham, Alexander King, Kiran Ashok, Bryan Poynter, Mary Beukemann, Richard Rice, Susan Gole, Valerie Shaner, Adarsh Conjeevaram, Michelle Ferrari, Narendrakumar Alappan, Steven Minear, Jaime Hernandez-Montfort, Syed Sohaib Nasim, Ravi Sunderkrishnan, Debasis Sahoo, Patrick S. Milligan, Sandeep K. Gupta, Joy M. Koglin, Regina Gibson, Lana Johnson, Felicia Preston, Crimson Scott, Bethany Nungester, Dana D Byrne, Christa A Schorr, Katie Grant, Katherine L Doktor, Maura C Porto, Olga Kaplan, James E. Siegler, III, Brian Schonewald, Ashley Woodford, Alan Tsai, Savina Reid, Kuntal Bhowmick, Saba Daneshpooy, Cyrus Mowdawalla, Trishna Akshay Dave, Wilhemina Kennedy, Connor Crudeli, Christopher Ferry, Long Nguyen, Sneha Modi, Niharika Padala, Pavan Jitendra Patel, Belle Lin, Lena Chatterjee, Jamie Qiuyun, Fan Mandi Liu, Rasagna Kota, Annesha Banerjee, Steven K. Daugherty, Sam Atkinson, Kelly Shrimpton, Sidney Ontai, Brian Contreras, Uzoma Obinwanko, Nneka Amamasi, Amir Sharafi, Sarah Lee, Zahia Esber, Chetna Jinjvadia, Raquel R Bartz, Vijay Krishnamoorthy, Bryan Kraft, Aaron Pulsipher, Eugene Friedman, Sachin Mehta, Margit Kaufman, Gregg Lobel, Nisha Gandhi, Amr Abdelaty, Elizabeth Shaji, Kiana Lim, Juan Marte, Dani Ashley Sosa, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Nicholas Perkins, Prera J. Roth, Banu Sivaraj, Haley Fulton, Madison G Herin, Marissa Crum, Morgan E. Fretwell, Emily-Rose Zhou, Christine Waller, Kara Kallies, Jonean Thorsen, Alec Fitzsimmons, Haley Olsen, Heda R. Dapul, Sourabh Verma, Alan Salas, Ariel Daube, Michelle Korn, Michelle Ramirez, Logi Rajagopalan, Laura Santos, Héctor Collazo Santiago, Ricardo Alan Hernandez, Norma Smalls, Asher G Bercow, Mark Shlomovich, Christine Crandall, Sasko Stojanovski, Kristin Johnson, Kelly Michienzi, Steven Q. Davis, Valentina Jovic, Max Masuda, Amanda Hayes, Katharine Nault, Michael Smith, William Snow, Riley Liptak, Hannah Durant, Valerie Pendleton, Alay Nanavati, Risa Mrozowsk, Namrata Nag, Jeff Brauer, Ashwin Dharmadhikari, Sahib Singh, Franco Laghi, Ghania Naeem, Andrew Wang, Kevin Bliden, Amit Rout, Jaime Barnes, Martin Gesheff, Asha Thomas, Melbin Thomas, Alicia R. Liendo, Jovan Milosavljevic, Kenan Abbasi, Nicholas B. Burley, Nicole Rapista, Samuel Amankwah, Sanjay K Poude, Saroj Timilsina, Sauradeep Sarkar, Oluwasayo Akinyosoye, Shashi K. Yalamanchili, Sheena Moorthy, Sonia Sugumar, Jonathan Ford, Martin C. Taylor, Charlotte Dunderdale, Alyssa Henshaw, Mary K. Brunk, Jessica Hagy, Shehryar Masood, Sushrutha Sridhar, Yuk Ming Liu, Sarah Zavala, Esther Shim, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Christine C. Junia, Robert Lichtenberg, Hasrat Sidhu, Diana Espinoza, Shelden Rodrigues, Maria Jose Zabala, Daniela Goyes, Ammu Susheela, Buddhi Hatharaliyadda, Naveen Rameshkumar, Amulya Kasireddy, Genessis Maldonado, Lisseth Beltran, Akshata Chaugule, Hassan Khan, Namrata Patil, Ruhi Patil, Rodrigo Cartin-Ceba, Ayan Sen, Fahimeh Talaei, Rahul Kashyap, Juan Pablo Domecq, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Romil Singh, Diana J. Valencia Morales, Abigail T. La Nou, Marija Bogojevic, Simon Zec, Devang Sanghavi, Pramod Guru, Pablo Moreno Franco, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu Lee Mateus, Siva Naga Yarrarapu, Nirmaljot Kaur, Abhisekh Giri, Mohammed Mustafa Hasan, Ashrita Donepudi, Syed Anjum Khan, Nitesh Kumar Jain, Thoyaja Koritala, Alexander Bastidas, Gabriela Orellana, Adriana Briceno Bierwirth, Eliana Milazzo, Juan Guillermo Sierra, Thao Dang, Rahul S Nanchal, Paul A Bergl, Jennifer L Peterson, Jessica Timmer, Kimberly Welker, Travis Yamanaka, Nicholas A. Barreras, Michael Markos, Anita Fareeduddin, Rohan Mehta, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Yasir Tarabichi, Adam Perzynski, Christine Wang, Dhatri Kotekal, Adriana C Briceno Bierwirth, Gabriela M Orellana, Gerardo Catalasan, Shohana Ahmed, Carlos F Matute, Ahmad Hamdan, Ivania Salinas, Genesis Del Nogal, Angel Tejada, Anna Eschler, Mary Hejna, Emily Lewandowski, Kristen Kusmierski, Clare Martin, Jen-Ting Chen, Aluko Hope, Zoe Tsagaris, Elise Ruen, Aram Hambardzumyan, Nasar A Siddiqi, Lesly Jurado, Lindsey Tincher, Carolyn Brown, Prithvi Sendi, Meghana Nadiger, Balagangadhar Totapally, Bhagat S. Aulakh, Sandeep Tripathi, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Neha Gupta, Brent R Brown, Tracy L Jones, Kassidy Malone, Lauren A Sinko, Amy B Harrell, Shonda C Ayers, Lisa M Settle, Taylor J Sears, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Roberta E. Redfern, Jessica Shoemaker, Jennifer Micham, Lynn Kenney, Gabriel Naimy, Victoria Schauf, Sara Utley, Holly Balcer, Kerry P. J. Pulver, Jennifer Yehle, Alicia Weeks, Terra Inman, Majdi Hamarshi, Jeannette Ploetz, Nick Bennett, Kyle Klindworth, Moustafa Younis, Adham Mohamed, Brian L. Delmonaco, Anthony Franklin, Mitchell Heath, Diane Barkas, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Shina Menon, John K McGuire, Deana Rich, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, John Lin, Cindy Terrill, Brock Montgomery, Sydney Reyes, Summer Reyes, Alex Plattner, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Umang Patel, Jordesha Hodge, Krunal Kumar Patel, Shivani Dalal, Himanshu Kavani, Sam Joseph, Michael A. Bernstein, Ian K. Goff, Matthew Naftilan, Amal Mathew, Deborah Williams, Sue Murdock, Maryanne Ducey, Kerianne Nelson, Jason Block, James Mitchel, Connor G O’Brien, Sylvan Cox, William Marx, Ioana Amzuta, Asad J. Choudhry, Mohammad T. Azam, Kristina L Carter, Michael A Olmos, Brittany M Parker, Julio Quintanilla, Tara A Craig, Brendon J Clough, Jeffrey T Jameson, Utpal S. Bhalala, Joshua Kuehne, Melinda Garcia, Morgan Beebe, Heather Herrera, Chris Fiack, Stephanie Guo, May Vawer, Beth Blackburn, Caleb Darby, Kristy Page, Amanda Brown, Jessie McAbee, Katherine A. Belden, Michael Baram, Devin M. Weber, Rosalie DePaola, Yuwei Xia, Hudson Carter, Aaron Tolley, Mary Barletta, Mark Steele, Laurie Kemble, Joshua L. Denson, A. Scott Gillet, Margo Brown, Rachael Stevens, Andrew Wetherbie, Kevin Tea, Mathew Moore, Abdurrahman Husain, Atul Malhotra, Qais Zawaydeh, Benjamin J Sines, Thomas J Bice, Emily A. Vail, Susannah Nicholson, Rachelle B. Jonas, AnnaRose E. Dement, William Tang, Mark DeRosa, Robert E. Villarreal, Rajany V. Dy, Alfredo Iardino, Jill Sharma, Richard Czieki, Julia Christopher, Ryan Lacey, Marwan Mashina, Kushal Patel, Erica C. Bjornstad, Nancy M. Tofil, Scott House, Isabella Aldana, Nikhil K. Meena, Jose D. Caceres, Nikhil K Meena, Sarenthia M. Epps, Harmeen Goraya, Kelsey R. Besett, Ryan James, Lana Y. Abusalem, Akash K. Patel, Lana S Hasan, Dina Gomaa, Michael Goodman, Devin Wakefield, Anthony Spuzzillo, John O. Shinn II, Robert MacLaren, Azra Bihorac, Tezcan Ozrazgat Baslanti, George Omalay, Haleh Hashemighouchani, Julie S. Cupka, Matthew M Ruppert, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Usman Nazir, Garrett Rampon, Jake Riggle, Nathan Dismang, Vicki Montgomery, Janice Sullivan, Sarah Morris, Jennifer Nason, Ozan Akca, Rainer Lenhardt, Rodrigo S. Cavallazzi, Ann Jerde, Alexa Black, Allison Polidori, Haily Griffey, Justin Winkler, Thomas Brenzel, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Pauline Park, Andrew Admon, Sinan Hanna, Rishi Chanderraj, Maria Pliakas, Ann Wolski, Jennifer Cirino, Dima Dandachi, Hariharan Regunath, Maraya N. Camazine, Grant. E. Geiger, Abdoulie O. Njai, Baraa M. Saad, Faraaz Ali Shah, Byron Chuan, Sagar L. Rawal, Manal Piracha, Joseph E. Tonna, Nicholas M. Levin, Kayte Suslavich, Rachel Tsolinas, Zachary T. Fica, Chloe R. Skidmore, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Nita Khandelwal, T. Eoin West, Ellen S. Caldwell, Lara Lovelace-Macon, Navya Garimella, Denisse B. Dow, Sreekanth R. Cheruku, Catherine Chen, Murtaza Akhter, Rania Abdul Rahman, Mary Mulrow, Erin M. Wilfong, Kelsi Vela, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Patrick G. Lyons, Andrew P Michelson, Sara S. Haluf, Lauren M. Lynch, Nguyet M. Nguyen, Aaron Steinberg, Nicholas Braus, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, Samuel Chakola, Kevin Sheth, Abdalla Ammar, Mahmoud Ammar, Victor Torres Lopez, Charles Dela Cruz,, Akhil Khosla, and Samir Gautam
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: OBJECTIVES:. To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN:. Prospective observational study. SETTING:. One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS:. Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS:. None. RESULTS:. Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0–81.0 yr) versus 61 years (48.0–72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, –0.84, –1.34, and –0.84; p < 0.001). CONCLUSIONS:. Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.
Published: 2022
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4. High-Dimensional Analysis Reveals Distinct Endotypes in Patients With Idiopathic Inflammatory Myopathies

Author: Erin M. Wilfong, Todd Bartkowiak, Katherine N. Vowell, Camille S. Westlake, Jonathan M. Irish, Peggy L. Kendall, Leslie J. Crofford, and Rachel H. Bonami
Subjects: idiopathic inflammatory myopathies (IIM), dermatomyositis (DM), polymyositis (PM), mass cytometry (CyTOF), immunophenotype, Immunologic diseases. Allergy, RC581-607
Abstract: The idiopathic inflammatory myopathies (IIM) are a rare clinically heterogeneous group of conditions affecting the skin, muscle, joint, and lung in various combinations. While myositis specific autoantibodies are well described, we postulate that broader immune endotypes exist in IIM spanning B cell, T cell, and monocyte compartments. This study aims to identify immune endotypes through detailed immunophenotyping of peripheral blood mononuclear cells (PBMCs) in IIM patients compared to healthy controls. We collected PBMCs from 17 patients with a clinical diagnosis of inflammatory myositis and characterized the B, T, and myeloid cell subsets using mass cytometry by time of flight (CyTOF). Data were analyzed using a combination of the dimensionality reduction algorithm t-distributed stochastic neighbor embedding (t-SNE), cluster identification, characterization, and regression (CITRUS), and marker enrichment modeling (MEM); supervised biaxial gating validated populations identified by these methods to be differentially abundant between groups. Using these approaches, we identified shared immunologic features across all IIM patients, despite different clinical features, as well as two distinct immune endotypes. All IIM patients had decreased surface expression of RP105/CD180 on B cells and a reduction in circulating CD3+CXCR3+ subsets relative to healthy controls. One IIM endotype featured CXCR4 upregulation across all cellular compartments. The second endotype was hallmarked by an increased frequency of CD19+CD21loCD11c+ and CD3+CD4+PD1+ subsets. The experimental and analytical methods we describe here are broadly applicable to studying other immune-mediated diseases (e.g., autoimmunity, immunodeficiency) or protective immune responses (e.g., infection, vaccination).
Published: 2022
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5. Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease

Author: Erin M. Wilfong and Rohit Aggarwal
Subjects: Diseases of the musculoskeletal system, RC925-935
Abstract: The antifibrotic therapies nintedanib and pirfenidone were first approved by the United States for the treatment of idiopathic pulmonary fibrosis in 2014. In 2020, nintedanib received U.S. Food and Drug Administration (FDA) approval for the treatment of all progressive fibrosing interstitial lung disease (ILD). Given that a major cause of mortality and morbidity in the idiopathic inflammatory myopathies (IIM) is progressive interstitial lung disease and respiratory failure, antifibrotic therapies may be useful as adjuvant to traditional immunosuppression. However, randomized controlled trials of antifibrotic therapies in IIM are lacking. The purpose of this review is to (1) summarize the mechanism of action of nintedanib and pirfenidone in ILD with possible role in IIM-ILD, (2) review the clinical data supporting their use in interstitial lung disease in general, and more specifically in connective tissue disease associated ILD, and (3) discuss the evidence and remaining challenges for using antifibrotic therapies in IIM-ILD.
Published: 2021
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6. Low Gut Microbial Diversity Augments Estrogen-Driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease

Author: Ozioma S. Chioma, Elizabeth Mallott, Binal Shah-Gandhi, ZaDarreyal Wiggins, Madison Langford, Andrew William Lancaster, Alexander Gelbard, Hongmei Wu, Joyce E. Johnson, Lisa Lancaster, Erin M. Wilfong, Leslie J. Crofford, Courtney G. Montgomery, Luc Van Kaer, Seth Bordenstein, Dawn C. Newcomb, and Wonder Puryear Drake
Subjects: estrogen, gut microbiome, lung fibrosis, sarcoidosis, Th17 cells, Cytology, QH573-671
Abstract: Although profibrotic cytokines, such as IL-17A and TGF-β1, have been implicated in the pathogenesis of interstitial lung disease (ILD), the interactions between gut dysbiosis, gonadotrophic hormones and molecular mediators of profibrotic cytokine expression, such as the phosphorylation of STAT3, have not been defined. Here, through chromatin immunoprecipitation sequencing (ChIP-seq) analysis of primary human CD4+ T cells, we show that regions within the STAT3 locus are significantly enriched for binding by the transcription factor estrogen receptor alpha (ERa). Using the murine model of bleomycin-induced pulmonary fibrosis, we found significantly increased regulatory T cells compared to Th17 cells in the female lung. The genetic absence of ESR1 or ovariectomy in mice significantly increased pSTAT3 and IL-17A expression in pulmonary CD4+ T cells, which was reduced after the repletion of female hormones. Remarkably, there was no significant reduction in lung fibrosis under either condition, suggesting that factors outside of ovarian hormones also contribute. An assessment of lung fibrosis among menstruating females in different rearing environments revealed that environments favoring gut dysbiosis augment fibrosis. Furthermore, hormone repletion following ovariectomy further augmented lung fibrosis, suggesting pathologic interactions between gonadal hormones and gut microbiota in relation to lung fibrosis severity. An analysis of female sarcoidosis patients revealed a significant reduction in pSTAT3 and IL-17A levels and a concomitant increase in TGF-β1 levels in CD4+ T cells compared to male sarcoidosis patients. These studies reveal that estrogen is profibrotic in females and that gut dysbiosis in menstruating females augments lung fibrosis severity, supporting a critical interaction between gonadal hormones and gut flora in lung fibrosis pathogenesis.
Published: 2023
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7. Risk Factors for Critical Coronavirus Disease 2019 and Mortality in Hospitalized Young Adults: An Analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Coronavirus Disease 2019 Registry

Author: Sandeep Tripathi, MD, MS, Imran A. Sayed, MD, Heda Dapul, MD, Jeremy S. McGarvey, MS, Jennifer A. Bandy, RN, Karen Boman, BS, Vishakha K. Kumar, MD, MBA, Vikas Bansal, MBBS, MPH, Lynn Retford, CAE, Sreekanth Cheruku, MD, MPH, Margit Kaufman, MD, FASA, Smith F. Heavner, MS, RN, Valerie C. Danesh, PhD, RN, Catherine A. St. Hill, DVM, PhD, Ashish K. Khanna, MD, Utpal Bhalala, MD, Rahul Kashyap, MBBS, MBA, Ognjen Gajic, MD, MS, Allan J. Walkey, MD, MS, Katja M. Gist, DO, MSc, for The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group, Jean-Baptiste Mesland, Pierre Henin, Hélène Petre, Isabelle Buelens, Anne-Catherine Gerard, Philippe Clevenbergh, Rolando Claure-Del Granado, Jose A. Mercado, Esdenka Vega-Terrazas, Maria F. Iturricha-Caceres, Ruben Garza, Eric Chu, Victoria Chan, Oscar Y Gavidia, Felipe Pachon, Yeimy A Sanchez, Mohamed El Kassas, Mohamed Badr, Ahmed Tawheed, Hend Yahia, Sierra-Hoffman, Fernando Valerio, Oscar Diaz, Jose Luis Ramos Coello, Guillermo Perez, Ana Karen Vallecillo Lizardo, Gabina María Reyes Guillen, Helin Archaga Soto, Mradul Kumar Daga, Munisha Agarwal, Ishan Rohtagi, Anusha Cherian, Sreejith Parameswaran, Magesh Parthiban, Menu Priya A., Girish Vadgaonkar, Rekha Ediga, Shilpa Basety, Shwetha Dammareddy, Phani Sreeharsha Kasumalla, Sridhar Papani, Mahesh Kamuram, Smitha S. Segu, Tuhin Chakraborty, Epcebha Joyce, Umamaheswara Raju, Janaki Manduva, Naresh Kolakani, Shreeja Sripathi, Sheetal Chaitanya, Surapaneni Krishna Mohan, Ekambaram Jyothisree, Kamlesh Kumar Agrawal, Vijendra Baghel, Kirti Kumar Patel, Nooshin Dalili, Mohsen Nafa, Sandeep Tripathi, Yuki Itagaki, Akira Kodate, Reina Suzuki, Yuki Takahashi, Koyo Moriki, Michihito Kyo, Masamitsu Sanui, Sho Horikita, Wataru Matsuda, Shu Tahara, Mineji Hayakawa, Kunihiko Maekawa, Takuya Shiga, Yudai Iwasaki, Abdulrahman AlFares, Rene Rodriguez-Gutierrez, Jose Gerardo Gonzalez-Gonzalez, Alejandro Salcido-Montenegro, Adrian Camacho-Ortiz, Fatimah Hassan-Hanga, Hadiza Galadanci, Abubakar Shehu Gezawa, Halima M. S. Kabara, Taiwo Gboluwaga Amole, Halima Kabir, Dalha Gwarzo, Haliru, Abdullahi S Ibrahim, Muhammad Sohaib Asghar, Mashaal Syed, Syed Anosh Ali Naqvi, Igor Borisovich Zabolotskikh, Konstantin Dmitrievich Zybin, Sergey Vasilevich Sinkov, Tatiana Sergeevna Musaeva, Marwa Ridha Amer, Mohammed Abdullah Bawazeer, Talal I. Dahhan, Eiad Kseibi, Abid Shahzad Butt, Syed Moazzum Khurshid, Muath Rabee, Mohammed Abujazar, Razan Alghunaim, Maal Abualkhair, Abeer Turki AlFirm, Razan K Alamoudi, Hassan M. AlSharif, Sarah A. Almazwaghi, Mohammed S Elsakran, Mohamed A Aid, Mouaz A Darwich, Omnia M Hagag, Salah A Ali, Alona rocacorba, Kathrine Supeña, Efren Ray Juane, Jenalyn Medina, Jowany Baduria, Mohammed A Almazyad, Mohammed I Alarifi, Jara M Macarambon, Ahmad Abdullah Bukhari, Hussain A. Albahrani, Kazi N Asfina, Kaltham M Aldossary, Predrag D Stevanovic, Dejan S Stojakov, Duska K Ignjatovic, Suzana C Bojic, Marina M Bobos, Irina B Nenadic, Milica S Zaric, Marko D Djuric, Vladimir R Djukic, Bojan Kovacevic, Jovana Bojicic, Marija Zdravkovic, Zoran Todorovic, Viseslav Popadic, Slobodan Klasnja, Santiago Y. Teruel, Belen C. Martin, Himat Sulaimonov, Firuza Khudonazarova, Nabi Bakhtibekov, Nekruz Jamshedov, Uluhan Sili, Huseyin Bilgin, Pinar Ay, Varsha P Gharpure, Usman Raheemi, Kenneth W. Dodd, Nicholas Goodmanson, Kathleen Hesse, Paige Bird, Chauncey Weinert, Nathan Schoenrade, Abdulrahman Altaher, Esmael Mayar, Matthew Aronson, Tyler Cooper, Monica Logan, Brianna Miner, Gisele Papo, Eric M. Siegal, Phyllis Runningen, Catherine A. St. Hill, Roman R. Melamed, David M. Tierney, Love A. Patel, Vino S. Raj, Barite U. Dawud, Narayana Mazumder, Abbey Sidebottom, Alena M. Guenther, Benjamin D. Krehbiel, Nova J. Schmitz, Stacy L. Jepsen, Abhijit A Raval, Andrea Franks, Katherine Irby, Ronald C. Sanders, Jr., Glenda Hefley, Anmol Kharbanda, Sunil Jhajhria, Zachary Fyffe, Stephen Capizzi, Bethany Alicie, Martha Green, Lori Crockarell, Amelia Drennan, Kathleen Dubuque, Tonya Fambrough, Nikole Gasaway, Briana Krantz, Peiman Nebi, Jan Orga, Margaret Serfass, Alina Simion, Kimberly Warren, Cassie Wheeler, CJ Woolman, Andrew S. Moyer, George M. Verghese, Andrea Sikora Newsome, Christy C. Forehand, Rebecca Bruning, Timothy W. Jones, Moldovan Sabov, Fatema Zaidi, Fiona Tissavirasingham, Dhatri Malipeddi, Jarrod M Mosier, Karen Lutrick, Beth Salvagio Campbell, Cathleen Wilson, Patrick Rivers, Jonathan Brinks, Mokenge Ndiva Mongoh, Boris Gilson, Donna Lee Armaignac, Don Parris, Maria Pilar Zuniga, Ilea Vargas, Viviana Boronat, Anneka Hutton, Navneet Kaur, Prashank Neupane, Nohemi Sadule-Rios, Lourdes M. Rojas, Aashish Neupane, Priscilla Rivera, Carlos Valle Carlos, Gregory Vincent, Mahesh Amin, Mary E Schelle, Amanda Steadham, Christopher M Howard, Cameron McBride, Jocelyn Abraham, Orlando Garner, Katherine Richards, Keegan Collins, Preethi Antony, Sindhu Mathew, Valerie C. Danesh, Gueorgui Dubrocq, Amber L. Davis, Marissa J Hammers, ill M. McGahey, Amanda C. Farris, Elisa Priest, Robyn Korsmo, Lorie Fares, Kathy Skiles, Susan M. Shor, Kenya Burns, Corrie A Dowell, Melody Flores, Lindsay Newman, Debora A Wilk, Jason Ettlinger, Jaccallene Bomar, Himani Darji, Alejandro Arroliga, Alejandro C Arroliga, Corrie A. Dowell, Gabriela Hope Conzales, Debora A. Wilk, Paras B. Khandhar, Elizabeth Kring, Valerie M. Banner-Goodspeed, Somnath Bose, Lauren E. Kelly, Melisa Joseph, Marie McGourty, Krystal Capers, Benjamin Hoenig, Maria C. Karamourtopoulos, Anica C. Law, Elias N. Baedorf Kassis, Allan J. Walkey, Sushrut S. Waikar, Michael A. Garcia, Mia Colona, Zoe Kibbelaar, Michael Leong, Daniel Wallman, Kanupriya Soni, Jennifer Maccarone, Joshua Gilman, Ycar Devis, Joseph Chung, Munizay Paracha, David N. Lumelsky, Madeline DiLorenzo, Najla Abdurrahman, Shelsey Johnson, Andrew M. Hersh, Stephanie L Wachs, Brittany S. Swigger, Lauren A. Sattler, Michael N. Moulton, Kimberly Zammit, J Patrick, William McGrath, Maya Loeffler, R Chilbert, Aaron S. Miller, Edwin L. Anderson, Rosemary Nagy, Ravali R. Inja, Raghavendra Tirupathi, Alymer Tang, Arshad Safi, Cindy Green, Jackie Newell, Rayan E. Ihle, Shelda A. Martin, Elaine A. Davis, Katja M. Gist, Imran A Sayed, John Brinton, Larisa Strom, Kathleen Chiotos, Allison M. Blatz, Giyoung Lee, Ryan H. Burnett, Guy I. Sydney, Danielle M. Traynor, Karissa Nauert, Annika Gonzalez, Mariel Bagley, Anita Santpurkar, Salim Surani, Joshua White, Aftab Khan, Rahul Dhahwal, Sreekanth Cheruku, Farzin Ahmed, Christopher Deonarine, Ashley Jones, Mohammad-Ali Shaikh, David Preston, Jeanette Chin, Vidula Vachharajani, Abhijit Duggal, Prabalini Rajendram, Omar Mehkri, Siddharth Dugar, Michelle Biehl, Gretchen Sacha, Stuart Houltham, Alexander King, Kiran Ashok, Bryan Poynter, Mary Beukemann, Richard Rice, Susan Gole, Valerie Shaner, Adarsh Conjeevaram, Michelle Ferrari, Narendrakumar Alappan, Steven Minear, Jaime Hernandez-Montfort, Syed Sohaib Nasim, Ravi Sunderkrishnan, Debasis Sahoo, Patrick S. Milligan, Sandeep K. Gupta, Joy M. Koglin, Regina Gibson, Lana Johnson, Felicia Preston, Crimson Scott, Bethany Nungester, Steven K. Daugherty, Sam Atkinson, Kelly Shrimpton, Sidney Ontai, Brian Contreras, Uzoma Obinwanko, Nneka Amamasi, Amir Sharafi, Sarah Lee, Zahia Esber, Chetna Jinjvadia, Kimberly Welker, Francis M. Maguire, Jessica Timmer, Raquel R Bartz, Vijay Krishnamoorthy, Bryan Kraft, Aaron Pulsipher, Eugene Friedman, Sachin Mehta, Margit Kaufman, Gregg Lobel, Nisha Gandhi, Amr Abdelaty, Elizabeth Shaji, Kiana Lim, Juan Marte, Dani Ashley Sosa, David P. Yamane, Ivy Benjenk, Nivedita Prasanna, Smith F. Heavner-Sullivan, Prera J. Roth, Banu Sivaraj, Haley Fulton, Madison G Herin, Marissa Crum, Morgan E. Fretwell, Emily-Rose Zhou, Christine Waller, Kara Kallies, Jonean Thorsen, Alec Fitzsimmons, Haley Olsen, Heda R. Dapul, Sourabh Verma, Alan Salas, Ariel Daube, Michelle Korn, Michelle Ramirez, Logi Rajagopalan, Laura Santos, Orma Smalls, Atul Malhotra, Abdurrahman Husain, Qais Zawaydeh, J.H. Steuernagle, Steven Q. Davis, Valentina Jovic, Max Masuda, Amanda Hayes, Katharine Nault, Michael Smith, William Snow, Riley Liptak, Hannah Durant, Valerie Pendleton, Alay Nanavati, Risa Mrozowsk, LiManoj K Gupta, Franscene E. Oulds, Akshay Nandavar, Yuk Ming Liu, Sarah Zavala, Esther Shim, Ronald A. Reilkoff, Julia A. Heneghan, Sarah Eichen, Lexie Goertzen, Scott Rajala, Ghislaine Feussom, Ben Tang, Christine C. Junia, Robert Lichtenberg, Hasrat Sidhu, Diana Espinoza, Shelden Rodrigues, Maria Jose Zabala, Daniela Goyes, Ammu Susheela, Buddhi Hatharaliyadda, Naveen Rameshkumar, Amulya Kasireddy, Genessis Maldonado, Lisseth Beltran, Akshata Chaugule, Hassan Khan, Namrata Patil, Ruhi Patil, Rodrigo Cartin-Ceba, Ayan Sen, Amanda Palacios, Giyth M. Mahdi, Rahul Kashyap, Ognjen Gajic, Vikas Bansal, Aysun Tekin, Amos Lal, John C. O’Horo, Neha N. Deo, Mayank Sharma, Shahraz Qamar, Cory J. Kudrna, Juan Pablo Domecq Garces, Abigail T. La Nou, Marija Bogojevic, Devang Sanghavi, Pramod Guru, Karthik Gnanapandithan, Hollie Saunders, Zachary Fleissner, Juan Garcia, Alejandra Yu Lee Mateus, Siva Naga Yarrarapu, Syed Anjum Khan, Juan Pablo Domecq, Nitesh Kumar Jain, Thoyaja Koritala, Alexander Bastidas, Gabriela Orellana, Adriana Briceno Bierwirth, Eliana Milazzo, Juan Guillermo Sierra, Thao Dang, Amy B. Christie, Dennis W. Ashley, Rajani Adiga, Rahul S Nanchal, Paul A Bergl, Jennifer L Peterson, Travis Yamanaka, Nicholas A. Barreras, Michael Markos, Anita Fareeduddin, Rohan Mehta, Chakradhar Venkata, Miriam Engemann, Annamarie Mantese, Yasir Tarabichi, Adam Perzynski, Christine Wang, Dhatri Kotekal, Adriana C Briceno Bierwirth, Gabriela M Orellana, Gerardo Catalasan, Shohana Ahmed, Carlos F Matute, Ahmad Hamdan, Ivania Salinas, Genesis Del Nogal, Angel Tejada, Anna Eschler, Mary Hejna, Emily Lewandowski, Kristen Kusmierski, Clare Martin, Jen-Ting Chen, Aluko Hope, Zoe Tsagaris, Elise Ruen, Aram Hambardzumyan, Prithvi Sendi, Meghana Nadiger, Balagangadhar Totapally, Bhagat S. Aulakh, Jennifer A. Bandy, Lisa M. Kreps, Dawn R. Bollinger, Roger Scott Stienecker, Andre G. Melendez, Tressa A. Brunner, Sue M Budzon, Jessica L. Heffernan, Janelle M. Souder, Tracy L. Miller, Andrea G. Maisonneuve, Roberta E. Redfern, Jessica Shoemaker, Jennifer Micham, Lynn Kenney, Gabriel Naimy, Sara Utley, Holly Balcer, Kerry P. J. Pulver, Jennifer Yehle, Alicia Weeks, Terra Inman, Brian L. Delmonaco, Anthony Franklin, Mitchell Heath, Antonia L. Vilella, Sara B. Kutner, Kacie Clark, Danielle Moore, Shina Menon, John K McGuire, Deana Rich, Harry L. Anderson, III, Dixy Rajkumar, Ali Abunayla, Jerrilyn Heiter, Howard A. Zaren, Stephanie J. Smith, Grant C. Lewis, Lauren Seames, Cheryl Farlow, Judy Miller, Gloria Broadstreet, John Lin, Cindy Terrill, Brock Montgomery, Sydney Reyes, Summer Reyes, Alex Plattner, Anthony Martinez, Micheal Allison, Aniket Mittal, Rafael Ruiz, Aleta Skaanland, Robert Ross, Umang Patel, Jordesha Hodge, KrunalKumar Patel, Shivani Dalal, Himanshu Kavani, Sam Joseph, Michael A. Bernstein, Ian K. Goff, Matthew Naftilan, Amal Mathew, Deborah Williams, Sue Murdock, Maryanne Ducey, Kerianne Nelson, Paul K Mohabir, Connor G O’Brien, Komal Dasani, William Marx, Ioana Amzuta, Asad J. Choudhry, Mohammad T. Azam, Kristina L Carter, Michael A Olmos, Brittany M Parker, Julio Quintanilla, Tara A Craig, Brendon J Clough, Jeffrey T Jameson, Neha Gupta, Tracy L Jones, Shonda C Ayers, Amy B Harrell, Dr.Brent R Brown, Utpal S. Bhalala, Joshua Kuehne, Melinda Garcia, Morgan Beebe, Heather Herrera, Chris Fiack, Stephanie Guo, May Vawer, Beth Blackburn, Megan Edwards, Caleb Darby, Kristy Page, Amanda Brown, Jessie McAbee, Katherine A. Belden, Michael Baram, Devin M. Weber, Rosalie DePaola, Yuwei Xia, Hudson Carter, Aaron Tolley, Mark Steele, Laurie Kemble, Joshua L. Denson, A. Scott Gillet, Margo Brown, Rachael Stevens, Andrew Wetherbie, Kevin Tea, Mathew Moore, Benjamin J Sines, Thomas J Bice, Emily A. Vail, Susannah Nicholson, Rachelle B. Jonas, AnnaRose E. Dement, William Tang, Mark DeRosa, Robert E. Villarreal, Rajany V. Dy, Alfredo Iardino, Jill Sharma, Richard Czieki, Julia Christopher, Ryan Lacey, Marwan Mashina, Kushal Patel, Erica C. Bjornstad, Nancy M. Tofil, Scott House, Isabella Aldana, Nikhil K. Meena, Jose D. Caceres, Nikhil K Meena, Sarenthia M. Epps, Harmeen Goraya, Kelsey R. Besett, Ryan James, Lana Y. Abusalem, Akash K. Patel, Lana S Hasan, Dina Gomaa, Michael Goodman, Devin Wakefield, Anthony Spuzzillo, John O. Shinn, II, Azra Bihorac, Tezcan Ozrazgat Baslanti, George Omalay, Haleh Hashemighouchani, Julie S. Cupka, Matthew M Ruppert, Patrick W. McGonagill, Colette Galet, Janice Hubbard, David Wang, Lauren Allan, Aditya Badheka, Madhuradhar Chegondi, Usman Nazir, Garrett Rampon, Jake Riggle, Nathan Dismang, Vicki Montgomery, Janice Sullivan, Sarah Morris, Jennifer Nason, Roger A. Alvarez, Amarilys Alarcon-Calderon, Marie Anne Sosa, Sunita K. Mahabir, Mausam J. Patel, Pauline Park, Andrew Admon, Sinan Hanna, Rishi Chanderraj, Maria Pliakas, Ann Wolski, Jennifer Cirino, Dima Dandachi, Hariharan Regunath, Maraya N. Camazine, Grant. E. Geiger, Abdoulie O. Njai, Baraa M. Saad, Faraaz Ali Shah, Byron Chuan, Sagar L. Rawal, Manal Piracha, Joseph E. Tonna, Nicholas M. Levin, Kayte Suslavich, Rachel Tsolinas, Zachary T. Fica, Chloe R. Skidmore, Renee D. Stapleton, Anne E. Dixon, Olivia Johnson, Sara S. Ardren, Stephanie Burns, Anna Raymond, Erika Gonyaw, Kevin Hodgdon, Chloe Housenger, Benjamin Lin, Karen McQuesten, Heidi Pecott-Grimm, Julie Sweet, Sebastian Ventrone, Nita Khandelwal, T. Eoin West, Ellen S. Caldwell, Lara Lovelace-Macon, Navya Garimella, Denisse B. Dow, Murtaza Akhter, Rania Abdul Rahman, Mary Mulrow, Erin M. Wilfong, Kelsi Vela, Ashish K. Khanna, Lynne Harris, Bruce Cusson, Jacob Fowler, David Vaneenenaam, Glen McKinney, Imoh Udoh, Kathleen Johnson, Patrick G. Lyons, Andrew P Michelson, Sara S. Haluf, Lauren M. Lynch, Nguyet M. Nguyen, Aaron Steinberg, Nicholas Braus, Vishwanath Pattan, Jessica Papke, Ismail Jimada, Nida Mhid, and Samuel Chakola
Subjects: Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract: IMPORTANCE:. Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES:. To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN, SETTINGS, AND PARTICIPANTS:. A retrospective cohort study of the Society of Critical Care Medicine’s Viral Infection and Respiratory Illness Universal Study registry. Patients 18–40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES:. Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS:. Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27–37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2–2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1–2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS:. Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.
Published: 2021
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8. High-Throughput Detection of Autoantigen-Specific B Cells Among Distinct Functional Subsets in Autoimmune Donors

Author: Bryan A. Joosse, James H. Jackson, Alberto Cisneros, Austin B. Santhin, Scott A. Smith, Daniel J. Moore, Leslie J. Crofford, Erin M. Wilfong, and Rachel H. Bonami
Subjects: B cells, B cell receptor (BCR), autoimmune disease, autoantigen, myositis, Sjogren’s syndrome, Immunologic diseases. Allergy, RC581-607
Abstract: Antigen-specific B cells (ASBCs) can drive autoimmune disease by presenting autoantigen to cognate T cells to drive their activation, proliferation, and effector cell differentiation and/or by differentiating into autoantibody-secreting cells. Autoantibodies are frequently used to predict risk and diagnose several autoimmune diseases. ASBCs can drive type 1 diabetes even when immune tolerance mechanisms block their differentiation into antibody-secreting cells. Furthermore, anti-histidyl tRNA synthetase syndrome patients have expanded IgM+ Jo-1-binding B cells, which clinically diagnostic IgG Jo-1 autoantibodies may not fully reflect. Given the potential disconnect between the pathologic function of ASBCs and autoantibody secretion, direct study of ASBCs is a necessary step towards developing better therapies for autoimmune diseases, which often have no available cure. We therefore developed a high-throughput screening pipeline to 1) phenotypically identify specific B cell subsets, 2) expand them in vitro, 3) drive them to secrete BCRs as antibody, and 4) identify wells enriched for ASBCs through ELISA detection of antibody. We tested the capacity of several B cell subset(s) to differentiate into antibody-secreting cells following this robust stimulation. IgM+ and/or IgD+, CD27- memory, memory, switched memory, and BND B cells secreted B cell receptor (BCR) as antibody following in vitro stimulation, whereas few plasmablasts responded. Bimodal responses were observed across autoimmune donors for IgM+ CD21lo and IgM- CD21lo B cells, consistent with documented heterogeneity within the CD21lo subset. Using this approach, we detected insulin-binding B cell bias towards CD27- memory and CD27+ memory subsets in pre-symptomatic type 1 diabetes donors. We took advantage of routine detection of Jo-1-binding B cells in Jo-1+ anti-histidyl tRNA synthetase syndrome patients to show that Jo-1-binding B cells and total B cells expanded 20-30-fold using this culture system. Overall, these studies highlight technology that is amenable to small numbers of cryopreserved peripheral blood mononuclear cells that enables interrogation of phenotypic and repertoire attributes of ASBCs derived from autoimmune patients.
Published: 2021
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9. Risk factors for mortality and mortality rates in interstitial lung disease patients in the intensive care unit

Author: Julio A. Huapaya, Erin M. Wilfong, Christopher T. Harden, Roy G. Brower, and Sonye K. Danoff
Subjects: Diseases of the respiratory system, RC705-779
Abstract: Data on interstitial lung disease (ILD) outcomes in the intensive care unit (ICU) is of limited value due to population heterogeneity. The aim of this study was to examine risk factors for mortality and ILD mortality rates in the ICU. We performed a systematic review using five databases. 50 studies were identified and 34 were included: 17 studies on various aetiologies of ILD (mixed-ILD) and 17 on idiopathic pulmonary fibrosis (IPF). In mixed-ILD, elevated APACHE score, hypoxaemia and mechanical ventilation are risk factors for mortality. No increased mortality was found with steroid use. Evidence is inconclusive on advanced age. In IPF, evidence is inconclusive for all factors except mechanical ventilation and hypoxaemia. The overall in-hospital mortality was available in 15 studies on mixed-ILD (62% in 2001–2009 and 48% in 2010–2017) and 15 studies on IPF (79% in 1993–2004 and 65% in 2005–2017). Follow-up mortality rate at 1 year ranged between 53% and 100%. Irrespective of ILD aetiology, mechanical ventilation is associated with increased mortality. For mixed-ILD, hypoxaemia and APACHE scores are also associated with increased mortality. IPF has the highest mortality rate among ILDs, but since 1993 the rate appears to be declining. Despite improving in-hospital survival, overall mortality remains high.
Published: 2018
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10. Distinct CD3+CD14+T Cell-Monocytes are dynamic complexes that harbor HIV and are increased with glucose intolerance

Author: Celestine N. Wanjalla, Joshua Simmons, Jared Oakes, Xiuqi Zhang, Cindy Nochowicz, Stephen Priest, Samuel S. Bailin, Christopher M. Warren, Mona Mashayekhi, Heather K. Beasley, Jian Wang, Leslie Meenderink, Quanhu Sheng, Joey Stolze, Rama Gangula, Abha Chopra, Curtis L. Gabriel, Tecla Temu, Suman Pakala, Erin M. Wilfong, Sara Gianella, Elizabeth J. Phillips, David G. Harrison, Antentor Hinton, Spyros A. Kalams, Simon A. Mallal, and John R. Koethe
Subjects: Article
Abstract: SummaryPersistent systemic inflammation in persons with HIV (PWH) is accompanied by an increased risk of metabolic disease. Yet, changes in the innate and adaptive immune system in PWH who develop metabolic disease remain poorly defined. Using unbiased approaches, we show that PWH with prediabetes/diabetes have a significantly higher proportion of circulating CD14+monocytes complexed to T cells. The complexed CD3+T cells and CD14+monocytes demonstrate functional immune synapses, increased expression of proinflammatory cytokines, and greater glucose utilization. Furthermore, these complexes harbor more latent HIV DNA compared to CD14+monocytes or CD4+T cells. Our results demonstrate that circulating CD3+CD14+T cell-monocyte pairs represent functional dynamic cellular interactions that likely contribute to inflammation and, in light of their increased proportion, may have a role in metabolic disease pathogenesis. These findings provide an incentive for future studies to investigate T cell-monocyte immune complexes as mechanistic in HIV cure and diseases of aging.Graphical AbstractHighlightsPersons with HIV and diabetes have increased circulating CD3+CD14+T cell-monocyte complexes.CD3+CD14+T cell-monocytes are a heterogenous group of functional and dynamic complexes.We can detect HIV in T cell-monocyte complexes.The proportion of CD3+CD14+T cell-monocyte complexes is positively associated with blood glucose levels and negatively with plasma IL-10 and CD4+T regulatory cells.
Published: 2023
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11. CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Author: Elise Rizzi, Erin M. Wilfong, April Barnado, Peggy L. Kendall, Leslie J. Crofford, Kaitlyn E Bunn, Rachel H. Bonami, Rosemarie Beckford Dudenhofer, Joyce E. Johnson, Katherine N. Vowell, and Narender Annapureddy
Subjects: medicine.medical_specialty, Pathology, Hematology, integumentary system, business.industry, Interstitial lung disease, General Medicine, respiratory system, medicine.disease, Peripheral blood mononuclear cell, General Biochemistry, Genetics and Molecular Biology, Scleroderma, respiratory tract diseases, Immunophenotyping, Internal medicine, medicine, Biomarker (medicine), Mass cytometry, skin and connective tissue diseases, business, Cytometry
Abstract: Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.
Published: 2021
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12. Intravenous immunoglobulin therapy for COVID-19 ARDS

Author: Michael A. Matthay and Erin M. Wilfong
Subjects: Pulmonary and Respiratory Medicine, Respiratory Distress Syndrome, ARDS, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Comment, MEDLINE, COVID-19, Immunoglobulins, Intravenous, medicine.disease, Respiration, Artificial, Intravenous Immunoglobulin Therapy, Immunology, medicine, Humans, business
Published: 2022
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13. Jo-1 autoantigen-specific B cells are skewed towards distinct functional B cell subsets in anti-synthetase syndrome patients

Author: Alberto rd Cisneros, Leslie J. Crofford, Jennifer J. Young-Glazer, Erin M. Wilfong, Scott A. Smith, and Rachel H. Bonami
Subjects: 0301 basic medicine, lcsh:Diseases of the musculoskeletal system, Autoimmune diseases, B-Lymphocyte Subsets, Autoimmunity, Biology, medicine.disease_cause, Peripheral blood mononuclear cell, Autoantigens, Flow cytometry, Ligases, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, B cell, Autoantibodies, B-Lymphocytes, medicine.diagnostic_test, Myositis, Autoantibody, Phenotype, In vitro, 030104 developmental biology, medicine.anatomical_structure, Immunology, Leukocytes, Mononuclear, lcsh:RC925-935, Ex vivo, 030215 immunology, Research Article, B lymphocytes
Abstract: Background Anti-Jo-1 autoantibodies which recognize histidyl-tRNA synthetase identify patients with the rare rheumatologic disease, anti-histidyl-tRNA synthetase syndrome (Jo-1 ARS), a phenotypically distinct subset of idiopathic inflammatory myopathies (IIM). Jo-1-binding B cells (JBCs) are implicated in disease pathogenesis, yet they have not been studied directly. We therefore aimed to characterize JBCs to better understand how they expand and function in Jo-1 ARS. Methods We enrolled 10 IIM patients diagnosed with Jo-1 ARS, 4 patients with non-Jo-1 IIM, and 8 age- and sex-matched healthy controls. We phenotypically characterized peripheral blood mononuclear cells (PBMCs) ex vivo using flow cytometry to define the B cell subsets in which JBCs reside. We further tested their ability to differentiate into antibody-secreting cells following stimulation in vitro. Results The majority of JBCs were IgM+ (not class-switched). Compared to non-JBCs in the same donors, JBCs contained a higher percentage of autoimmune-prone CD21lo cells and were increased in the CD21lo IgM+ IgD− CD27+ memory subset relative to healthy donor B cells. Whereas non-JBCs were present in the anergic BND B cell subset, JBCs were nearly absent from this compartment. JBCs were detected among plasmablasts in some donors, but a reduced frequency of JBCs differentiated into CD38hi24− plasmablasts compared to non-JBCs present in the same wells following in vitro stimulation. Conclusions JBCs are enriched for autoimmune-prone CD21lo B cells, some of which exhibit a memory phenotype in the peripheral repertoire of Jo-1 ARS patients. JBCs undergo limited class switch and show reduced capacity to differentiate into antibody-secreting cells. This suggests complex B cell biology exists beyond class-switched cells that differentiate to secrete anti-Jo-1 autoantibody (i.e., what is captured through serum autoantibody studies). New Jo-1 ARS therapies should thus ideally target non-class-switched JBCs in addition to those that have undergone IgG class-switching to most effectively block cross-talk with autoreactive T cells.
Published: 2021

14. Single-Cell Profiling of the Antigen-Specific Response to BNT162b2 SARS-CoV-2 RNA Vaccine

Author: Robert H. Carnahan, Sierra Barone, Rachel H. Bonami, Andrea R. Shiakolas, Jonathan M. Irish, Camille S. Westlake, Ariana Paulo, Ivelin S. Georgiev, Erin M Wilfong, James E. Crowe, Lauren M. Walker, Debolanle O. Dahunsi, Nagarajan Raju, Kevin J Kramer, Kelsey Voss, Jeffrey C. Rathmell, Samuel Schaefer, Naveenchandra Suryadevara, Caroline E. Roe, and Steven C. Wall
Subjects: Proteomics, COVID-19 Vaccines, Lymphocyte, Population, General Physics and Astronomy, CD8-Positive T-Lymphocytes, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Article, Immunity, medicine, Humans, Mass cytometry, education, B cell, BNT162 Vaccine, education.field_of_study, Vaccines, Synthetic, Multidisciplinary, biology, SARS-CoV-2, RNA, COVID-19, Breakthrough infection, General Chemistry, Virology, medicine.anatomical_structure, Immunoglobulin G, biology.protein, RNA, Viral, mRNA Vaccines, Antibody
Abstract: SUMMARYRNA-based vaccines against SARS-CoV-2 are critical to limiting COVID-19 severity and spread. Cellular mechanisms driving antigen-specific responses to these vaccines, however, remain uncertain. We used single-cell technologies to identify and characterized antigen-specific cells and antibody responses to the RNA vaccine BNT162b2 in longitudinal samples from a cohort of healthy donors. Mass cytometry and machine learning pinpointed a novel expanding, population of antigen-specific non-canonical memory CD4+ and CD8+ T cells. B cell sequencing suggested progression from IgM, with apparent cross-reactivity to endemic coronaviruses, to SARS-CoV-2-specific IgA and IgG memory B cells and plasmablasts. Responding lymphocyte populations correlated with eventual SARS-CoV-2 IgG and a donor lacking these cell populations failed to sustain SARS-CoV-2-specific antibodies and experienced breakthrough infection. These integrated proteomic and genomic platforms reveal an antigen-specific cellular basis of RNA vaccine-based immunity.ONE SENTENCE SUMMARYSingle-cell profiling reveals the cellular basis of the antigen-specific response to the BNT162b2 SARS-CoV-2 RNA vaccine.
Published: 2021

15. High-dimensional analysis reveals abnormal B cell subsets associated with specific changes to circulating T and myeloid cell populations in patients with idiopathic inflammatory myopathies

Author: Erin M. Wilfong, Peggy L. Kendall, Jonathan M. Irish, Camille S. Westlake, Todd Bartkowiak, Rachel H. Bonami, Leslie J. Crofford, and Katherine N. Vowell
Subjects: education.field_of_study, Myeloid, biology, business.industry, T cell, Population, CD38, Peripheral blood mononuclear cell, CD19, medicine.anatomical_structure, Immunophenotyping, Immunology, medicine, biology.protein, education, business, B cell
Abstract: ObjectivesThe idiopathic inflammatory myopathies (IIM) are a clinically heterogeneous group of conditions affecting the skin, muscle, joint, and lung in various combinations. This study aims to investigate the immunologic heterogeneity through detailed immunophenotyping of peripheral blood mononuclear cells (PBMCs) in IIM patients and healthy controls.MethodsWe collected PBMCs from 17 patients with a clinical diagnosis of inflammatory myositis in the inpatient or outpatient setting and performed immunophenotyping using mass cytometry by time of flight (CyTOF) to simultaneously characterize B, T, and myeloid cell subsets. Data were analyzed using a combination of supervised biaxial gating and unsupervised clustering algorithms including t-distributed stochastic neighbor embedding (tSNE), cluster identification, characterization, and regression (CITRUS), and marker enrichment modeling (MEM).ResultsWe identified two distinct immune signatures amongst IIM patients. In one signature, increased CD19+CXCR4hiCCR7hi cells correlated with increased CD3+CXCR4hiCD38hi (r=0.62, p=0.009) and CD14+CD16-CXCR4+CD38+HLADR-(r=0.61, p=0.01) populations. In the second signature, increased CD19+CD21loCD11c+ cells correlated with an increased CD3+CD4+PD1+ (r=0.60, p=0.01) population. Other shared immunologic features amongst IIM patients compared to healthy controls included decreased surface expression of RP105/CD180 on B cells (median mass intensity 39.9 ± 16.0 v. 60.9 ± 20.1, p=0.002). In the T cell compartment, all circulating CD3+CXCR3+ subsets (2.7 ± 2.4 v. 9.6 ± 8.1% of all PBMCs, p=0.0004) were reduced.ConclusionBased on circulating B cell phenotype, we identified two distinct immunologic signatures in IIM patients. Future work is needed to determine the significance of these immune signatures for clinical manifestations and treatment responses.
Published: 2021
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16. Anti-tRNA synthetase syndrome interstitial lung disease: A single center experience

Author: Erin M. Wilfong, Gabriel Schroeder, Narender Annapureddy, Bret K. Sohn, Erin A. Gillaspie, Leslie J. Crofford, Jennifer J. Young-Glazer, April Barnado, and Rosemarie Beckford Dudenhofer
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Single Center, Gastroenterology, Dermatomyositis, Article, Amino Acyl-tRNA Synthetases, 03 medical and health sciences, Idiopathic pulmonary fibrosis, FEV1/FVC ratio, 0302 clinical medicine, Usual interstitial pneumonia, Internal medicine, medicine, Rheumatoid factor, Humans, 030212 general & internal medicine, Myositis, Autoantibodies, Retrospective Studies, business.industry, Interstitial lung disease, Retrospective cohort study, respiratory system, medicine.disease, Connective tissue disease, respiratory tract diseases, 030228 respiratory system, business, Lung Diseases, Interstitial
Abstract: BackgroundRecognition of Anti tRNA synthetase (ARS) related interstitial lung disease (ILD) is key to ensuring patients have prompt access to immunosuppressive therapies. The purpose of this retrospective cohort study was to identify factors that may delay recognition of ARS-ILD.MethodsPatients seen at Vanderbilt University Medical Center (VUMC) between 9/17/2017-10/31/2018 were included in this observational cohort. Clinical and laboratory features were obtained via chart abstraction. Kruskal-Wallis ANOVA, Mann-Whitney U, and Fisher’s exact t tests were utilized to determine statistical significance.ResultsPatients with ARS were found to have ILD in 51.9% of cases, which was comparable to the frequency of ILD in systemic sclerosis (59.5%). The severity of FVC reduction in ARS (53.2%) was comparable to diffuse cutaneous systemic sclerosis (56.8%, p=0.48) and greater than dermatomyositis (66.9%, p=0.005) or limited cutaneous systemic sclerosis (lcSSc, 71.8%, p=0.005). Frank honeycombing was seen with ARS antibodies but not other myositis autoantibodies. ARS patients were more likely to first present to a pulmonary provider in a tertiary care setting (53.6%), likely due to fewer extrapulmonary manifestations. Only 33% of ARS-ILD were anti-nuclear antibody, rheumatoid factor, or anti-cyclic citrullinated peptide positive. Patients with ARS-ILD had a two-fold longer median time to diagnosis compared to other myositis-ILD patients (11.0 months, IQR 8.5 to 43 months vs. 5.0 months, IQR 3.0 to 9.0 months, p=0.003).ConclusionsARS patients without prominent extra-pulmonary manifestations are at high risk for not being recognized as having a connective tissue disease related ILD and miscategorized as UIP/IPF without comprehensive serologies.
Published: 2021

17. Systemic soluble Programmed Death-Ligand 1 levels in sarcoidosis subjects does not vary with disease progression

Author: Wonder P. Drake, Wendi R. Mason, Erin M. Wilfong, Binal Shah-Gandhi, O.S. Chioma, and K. Abel
Subjects: medicine.medical_specialty, Vital capacity, medicine.diagnostic_test, business.industry, Interstitial lung disease, respiratory system, medicine.disease, Gastroenterology, Scleroderma, respiratory tract diseases, FEV1/FVC ratio, Idiopathic pulmonary fibrosis, Bronchoalveolar lavage, Internal medicine, medicine, Biomarker (medicine), Sarcoidosis, business
Abstract: Interaction of programmed cell death 1 (PD-1) receptor and its ligand 1 (PD-L1) is well studied in the field of fibrotic lung diseases, supporting its use as a biomarker of progression of interstitial lung disease. Anti PD-L1 therapy has shown effectiveness in improvement of many malignancies and murine models of autoimmune fibrotic lung diseases. Higher PD-1 expression on T cells and PD-L1 expression on human lung fibroblasts are known to contribute towards severity in sarcoidosis and idiopathic pulmonary fibrosis (IPF), respectively. The focus of this investigation was to determine if soluble form of PD-L1 (sPD-L1) serves as predictive biomarker of disease severity in interstitial lung disease (ILD), such as scleroderma, sarcoidosis and IPF. Comparison of local environments, such as bronchoalveolar lavage, revealed significantly higher sPD-L1 levels compared to systemic environments, such as peripheral blood (p=0.001, paired two-tailed Student’s t test). Investigation of serum samples of healthy control, IPF, scleroderma and sarcoidosis patients reveal significantly higher levels in sarcoidosis and IPF patients, compared to patients with scleroderma (p=0.001; p=0.02, one-way ANOVA with Tukey’s respectively). Comparison of serum levels between sarcoidosis patients and healthy controls revealed no significant differences (p=0.09, unpaired two-tailed t test). In addition, comparison of physiologic parameters, such as percent predicated Forced Vital Capacity (FVC) and sPD-L1 levels in sarcoidosis and IPF patients revealed no correlation. These observations suggest that sPD-L1 will not serve as a biomarker of sarcoidosis disease severity. Additional investigation of sPD-L1 in local environments is warranted.
Published: 2021
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18. Severity of illness scores at presentation predict ICU admission and mortality in COVID-19

Author: Jonathan D Casey, Christine M. Lovly, Li-Ching Huang, Matthew W. Semler, Brian I. Rini, Erin A. Gillaspie, Erin M. Wilfong, and Yu Shyr
Subjects: medicine.medical_specialty, business.industry, Retrospective cohort study, Emergency department, Critical Care and Intensive Care Medicine, Intensive care unit, Article, law.invention, Clinical trial, Acute physiology and chronic health evaluation II (APACHE-II), qSOFA, law, Intensive care, health care utilization, Severity of illness, Health care, Emergency medicine, Emergency Medicine, Clinical endpoint, medicine, coronavirus disease 2019 (COVID-19), intensive care unit (ICU), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), business
Abstract: Background The COVID-19 pandemic has overwhelmed hospital systems in multiple countries and necessitated caring for patients in atypical healthcare settings. The goal of this study was to ascertain if the conventional critical care severity scores qSOFA, SOFA, APACHE-II, and SAPS-II could predict which patients admitted to the hospital from an emergency department would eventually require intensive care. Methods This single-center, retrospective cohort study enrolled patients admitted to Vanderbilt University Hospital from the emergency room with symptomatic, confirmed COVID-19 infection between March 8, 2020 through May 15, 2020. Clinical phenotyping was performed by chart abstraction, and the correlation of the qSOFA, SOFA, APACHE-II, and SAPS-II scores for the primary endpoint of ICU admission and secondary endpoint of in-hospital mortality was evaluated. Results During the study period, 128 patients were admitted to Vanderbilt University Hospital from the emergency room with COVID-19. Of these, 39 patients eventually required intensive care; the remaining 89 were discharged from the medical ward. All severity of illness scores demonstrated at least moderate ability to identify patients who would die or require ICU admission. Of the three severity of illness scores assessed, the APACHE-II score performed best with an AUC of 0.851 (95% CI: 0.786 to 0.917) for identifying patient that would require ICU admission. No patient with an APACHE-II score at the time of presentation less than 8 or qSOFA of 0 required intensive care unit (ICU) admission. All patients with an APACHE-II score less than 10 or qSOFA score of 0 survived to hospital discharge. Conclusions The APACHE-II score accurately predicts the eventual need for ICU admission. This may allow for risk-stratification of patients safe to treat in alternative health care settings and prognostic enrichment to accelerate clinical trials of COVID-19 therapies.
Published: 2021

19. Myositis and Systemic Sclerosis Spectrum IPAF Patients Are More Likely to Respond Favorably to Immunosuppression

Author: Narender Annapureddy, Gabriel Schroeder, April Barnado, R.B. Dudenhofer, Erin M Wilfong, and Leslie J. Crofford
Subjects: business.industry, medicine.medical_treatment, Immunology, medicine, Immunosuppression, medicine.disease, business, Myositis
Published: 2020
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20. Interstitial Pneumonia With Autoimmune Features

Author: Robert J. Lentz, Timothy S. Blackwell, Adam Guttentag, Leslie J. Crofford, Erin M. Wilfong, Peggy L. Kendall, James J. Tolle, Joyce E. Johnson, and Jonathan A. Kropski
Subjects: Male, medicine.medical_specialty, Immunology, Context (language use), Antisynthetase syndrome, Disease, Article, Autoimmune Diseases, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Pulmonary Medicine, medicine, Humans, Immunology and Allergy, Connective Tissue Diseases, Intensive care medicine, Myositis, 030203 arthritis & rheumatology, business.industry, Interstitial lung disease, medicine.disease, Connective tissue disease, Pulmonology, 030228 respiratory system, Female, Lung Diseases, Interstitial, business
Abstract: Interstitial lung disease (ILD) remains a cause of significant morbidity and mortality in patients with connective tissue disease (CTD)-associated ILD. While some patients meet clear classification criteria for a systemic rheumatic disease, a subset of patients do not meet classification criteria but still benefit from immunosuppressive therapy. In 2015, the American Thoracic Society and European Respiratory Society described classification criteria for interstitial pneumonia with autoimmune features (IPAF) to identify patients with lung-predominant CTD who lack sufficient features of a systemic rheumatic disease to meet classification criteria. Although these criteria are imperfect, they are an important attempt to classify the patient with undifferentiated disease for future study. Rheumatologists play a key role in the evaluation of potential IPAF in patients, especially as many patients with a myositis-spectrum disease (e.g., non-Jo-1 antisynthetase syndrome, anti-melanoma differentiation-associated protein 5 antibody inflammatory myositis, or anti-PM/Scl antibody-associated inflammatory myositis) would be classified under IPAF using the currently available criteria for inflammatory myositis, and would therefore benefit from rheumatologic comanagement. The aim of this review was to describe the historical context that led to the development of these criteria and to discuss the limitations of the current criteria, diagnostic challenges, treatment options, and strategies for disease monitoring.
Published: 2018
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21. Proinflammatory cytokines and ARDS pulmonary edema fluid induce CD40 on human mesenchymal stromal cells-A potential mechanism for immune modulation

Author: Jae-Woo Lee, Matthew Schwede, Erin M. Wilfong, Eréne C. Niemi, Mary C. Nakamura, Xiaohui Fang, Giselle Y. Lopez, Roxanne H. Croze, Michael A. Matthay, and Zhao, You-Yang
Subjects: 0301 basic medicine, Lipopolysaccharides, Male, ARDS, Critical Care and Emergency Medicine, Transcription, Genetic, Pulmonology, Physiology, Gene Expression, 0302 clinical medicine, Medical Conditions, Spectrum Analysis Techniques, Stem Cell Research - Nonembryonic - Human, Immune Physiology, Cellular types, Medicine and Health Sciences, Edema, Lung, Acute Respiratory Distress Syndrome, Immune Response, Cells, Cultured, Respiratory Distress Syndrome, Innate Immune System, Multidisciplinary, Cultured, Transdifferentiation, Immune cells, Pulmonary edema, Flow Cytometry, Up-Regulation, Spectrophotometry, Cytokines, White blood cells, Medicine, Female, Cytophotometry, medicine.symptom, Transcription, Bronchoalveolar Lavage Fluid, Research Article, Cell biology, Blood cells, endocrine system, Stromal cell, General Science & Technology, Cells, Science, Immunology, T cells, Inflammation, Cytotoxic T cells, Research and Analysis Methods, Proinflammatory cytokine, 03 medical and health sciences, Paracrine signalling, Respiratory Disorders, Rare Diseases, Signs and Symptoms, Genetic, Respiratory Failure, medicine, Genetics, Humans, CD40 Antigens, business.industry, Mesenchymal stem cell, Biology and Life Sciences, Mesenchymal Stem Cells, Molecular Development, Stem Cell Research, medicine.disease, equipment and supplies, 030104 developmental biology, Animal cells, Cyclooxygenase 2, Immune System, Cell Transdifferentiation, Cancer research, Clinical Medicine, business, Cell Adhesion Molecules, 030215 immunology, Developmental Biology
Abstract: Human mesenchymal stem/stromal cells (hMSCs) are a promising therapy for acute respiratory distress syndrome (ARDS) and other inflammatory conditions. While considerable research has focused on paracrine effects and mitochondrial transfer that improve lung fluid balance, hMSCs are well known to have immunomodulatory properties as well. Some of these immunomodulatory properties have been related to previously reported paracrine effectors such as indoleamine-2,3-dioxygenase (IDO), but these effects cannot fully account for cell-contact dependent immunomodulation. Here, we report that CD40 is upregulated on hMSCs under the same conditions previously reported to induce IDO. Further, CD40 transcription is also upregulated on hMSCs by ARDS pulmonary edema fluid but not by hydrostatic pulmonary edema fluid. Transcription of CD40, as well as paracrine effectors TSG6 and PTGS2 remained significantly upregulated for at least 12 hours after withdrawal of cytokine stimulation. Finally, induction of this immune phenotype altered the transdifferentiation of hMSCs, one of their hallmark properties. CD40 may play an important role in the immunomodulatory effects of hMSCs in ARDS and inflammation.
Published: 2020

22. Effect of a fluid bolus on cardiovascular collapse among critically ill adults undergoing tracheal intubation (PrePARE): a randomised controlled trial

Author: David R Janz, Jonathan D Casey, Matthew W Semler, Derek W Russell, James Dargin, Derek J Vonderhaar, Kevin M Dischert, Jason R West, Susan Stempek, Joanne Wozniak, Nicholas Caputo, Brent E Heideman, Aline N Zouk, Swati Gulati, William S Stigler, Itay Bentov, Aaron M Joffe, Todd W Rice, Ross Hoffman, Naveen Turlapati, Sneha Samant, Page Clark, Amita Krishnan, Joseph Gresens, Cody Hill, Bobby Matthew, Jason Henry, Jason Miller, Rose Paccione, Abdulla Majid-Moosa, Jairo I Santanilla, Erin M Wilfong, Justin C Hewlett, Stephen J Halliday, V Eric Kerchberger, Ryan M Brown, Luis E Huerta, Christopher M Merrick, Thomas Atwater, Emily G Kocurek, Andrew C McKown, Nichelle I Winters, Luke E Habegger, Matthew F Mart, Jeannette Z Berg, Christina C Noblit, Lisa N Flemmons, Kevin Dischert, Aaron Joffe, Trefan Archibald, Alejandro Arenas, Camelia Baldridge, Gaurav Bansal, Christopher Barnes, Nicholas Bishop, Beth Bryce, Laura Byrne, Rachel Clement, Carla DeLaCruz, Priya Deshpande, Zi Gong, John Green, Austin Henry, Andrew Herstein, Jessica Huang, Jake Heier, Bonnie Jenson, Lynn Johnston, Cara Langeland, Calvin Lee, Alex Nowlin, Travis Reece-Nguyen, Hunter Schultz, Graeme Segal, Ian Slade, Stuart Solomon, Sarah Stehpey, Robin Thompson, David Trausch, Carson Welker, Raymond Zhang, Derek Russell, Aline Zouk, William Stigler, Jason Fain, Bryan Garcia, David Lafon, Chao He, James O'Connor, David Campbell, Jordan Powner, Samuel McElwee, Cristina Bardita, Kevin D'Souza, G Bruno Pereira, Sarah Robinson, Scott Blumhof, Piyanuch Pataramekin, Dhruv Desai, Ekaterina Yayarovich, Robert DeMatteo, Sandeep Somalaraiu, Christopher Adler, Courtney Reid, Michael Plourde, Jordan Winnicki, Timothy Noland, Tamar Geva, Lee Gazourian, Avignat Patel, Khaled Eissa, Joshua Giacotto, Daniel Fitelson, Michael Colancecco, Anthony Gray, Mary Ryan, Thomas Parry, Benjamin Azan, Ali Khairat, Renee Morton, David Lewandowski, and Carlos Vaca
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_treatment, Critical Illness, Population, law.invention, Bolus (medicine), Randomized controlled trial, law, Intubation, Intratracheal, Medicine, Intubation, Humans, Vasoconstrictor Agents, education, Infusions, Intravenous, Aged, education.field_of_study, business.industry, Critically ill, Tracheal intubation, Shock, Emergency department, Crystalloid Solutions, Middle Aged, Respiration, Artificial, Blood pressure, Anesthesia, Fluid Therapy, Female, business
Abstract: Tracheal intubation is common in the care of critically ill adults and is frequently complicated by hypotension, cardiac arrest, or death. We aimed to evaluate administration of an intravenous fluid bolus to prevent cardiovascular collapse during intubation of critically ill adults.We did a pragmatic, multicentre, unblinded, randomised trial in nine sites (eight ICUs and one emergency department) around the USA. Critically ill adults (≥18 years) undergoing tracheal intubation were randomly assigned (1:1, block sizes of 2, 4, and 6, stratified by study site) to either an intravenous infusion of 500 mL of crystalloid solution or no fluid bolus. The primary outcome, assessed in the intention-to-treat population, was cardiovascular collapse, defined as a new systolic blood pressure65 mm Hg; new or increased vasopressor receipt between induction and 2 min after tracheal intubation; or cardiac arrest or death within 1 h of tracheal intubation. Adverse events were assessed in the as-treated population. This trial, which is now complete, is registered with ClinicalTrials.gov, number NCT03026777.Patients were enrolled from Feb 6, 2017, to Jan 9, 2018, when the data and safety monitoring board stopped the trial on the basis of futility. By trial termination, 337 (63%) of 537 screened adults had been randomly assigned. Cardiovascular collapse occurred in 33 (20%) of 168 patients in the fluid bolus group compared with 31 (18%) of 169 patients in the no fluid bolus group (absolute difference 1·3% [95% CI -7·1% to 9·7%]; p=0·76). The individual components of the cardiovascular collapse composite outcome did not differ between groups (new systolic blood pressure65 mm Hg 11 [7%] in the bolus group vs ten [6%] in the no-bolus group, new or increased vasopressor 32 [19%] vs 31 [18%], cardiac arrest within 1 h seven [4%] vs two [1%], death within 1 h of intubation two [1%] vs one [1%]). In-hospital mortality was not significantly different in the fluid bolus group (48 [29%]) compared with no fluid bolus (59 [35%]).Administration of an intravenous fluid bolus did not decrease the overall incidence of cardiovascular collapse during tracheal intubation of critically ill adults compared with no fluid bolus in this trial.US National Institutes of Health.
Published: 2019

23. 007. ANCA-ASSOCIATED INTERSTITIAL LUNG DISEASE: THE VANDERBILT EXPERIENCE

Author: Erin M Wilfong, Narender Annapureddy, Kevin Byram, and Leslie J. Crofford
Subjects: Pathology, medicine.medical_specialty, Rheumatology, business.industry, Interstitial lung disease, medicine, Pharmacology (medical), medicine.disease, business
Published: 2019
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24. Reply

Author: Leslie J. Crofford, Erin M. Wilfong, and Jonathan A. Kropski
Subjects: Rheumatology, business.industry, Immunology, Immunology and Allergy, Medicine, Interstitial pneumonia, Sarcoidosis, business, medicine.disease, Hypersensitivity pneumonitis
Published: 2019
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25. Reply

Author: Kevin Byram, Leslie J. Crofford, and Erin M. Wilfong
Subjects: 030203 arthritis & rheumatology, medicine.medical_specialty, business.industry, Immunology, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Rheumatology, Pulmonary Medicine, medicine, Humans, Immunology and Allergy, Interstitial pneumonia, Lung Diseases, Interstitial, Intensive care medicine, business
Published: 2019
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26. Effects of bone marrow-derived mesenchymal stromal cells on gene expression in human alveolar type II cells exposed to TNF-α , IL-1β , and IFN-γ

Author: Erin M. Wilfong, Xiaohui Fang, Claudia C. dos Santos, Michael A. Matthay, Rachel L. Zemans, Patty J. Lee, and Matthew Schwede
Subjects: Adult, Male, 0301 basic medicine, Physiology, Immunology, Interleukin-1beta, alveolar epithelial cells, Proinflammatory cytokine, Extracellular matrix, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Physiology (medical), Gene expression, medicine, Humans, Cells, Cultured, Original Research, Respiratory Conditions Disorder and Diseases, Principal Component Analysis, Acute respiratory distress syndrome, Tumor Necrosis Factor-alpha, Microarray analysis techniques, Chemistry, Gene Expression Profiling, Mesenchymal stem cell, Mesenchymal Stem Cells, Pulmonary Surfactants, respiratory system, cytokines, 3. Good health, Pulmonary Alveoli, Gene expression profiling, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, Cancer research, Cellular Physiology, Bone marrow, Inflammation Mediators, mesenchymal stromal cells, 030217 neurology & neurosurgery
Abstract: The acute respiratory distress syndrome (ARDS) is common in critically ill patients and has a high mortality rate. Mesenchymal stromal cells (MSCs) have demonstrated therapeutic potential in animal models of ARDS, and their benefits occur in part through interactions with alveolar type II (ATII) cells. However, the effects that MSCs have on human ATII cells have not been well studied. Using previously published microarray data, we performed genome‐wide differential gene expression analyses of human ATII cells that were (1) unstimulated, (2) exposed to proinflammatory cytokines (CytoMix), or (3) exposed to proinflammatory cytokines plus MSCs. Findings were validated by qPCR. Alveolar type II cells differentially expressed hundreds of genes when exposed either to proinflammatory cytokines or to proinflammatory cytokines plus MSCs. Stimulation with proinflammatory cytokines increased expression of inflammatory genes and downregulated genes related to surfactant function and alveolar fluid clearance. Some of these changes, including expression of some cytokines and genes related to surfactant, were reversed by exposure to MSCs. In addition, MSCs induced upregulation of other potentially beneficial genes, such as those related to extracellular matrix remodeling. We confirmed several of these gene expression changes by qPCR. Thus, ATII cells downregulate genes associated with surfactant and alveolar fluid clearance when exposed to inflammatory cytokines, and mesenchymal stromal cells partially reverse many of these gene expression changes.
Published: 2018
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27. Autoreactive-prone CD21lo B cells increased in scleroderma patients with interstitial lung disease

Author: Katherine Nicholas Vowell, Erin M. Wilfong, Leslie J. Crofford, and Peggy L. Kendall
Subjects: Immunology, Immunology and Allergy
Abstract: Systemic sclerosis (SSc) is a devastating autoimmune disease characterized by fibrosis of the skin and vital organs. The pathogenesis of SSc is unknown, but detection of autoantibodies in >90% of SSc patients suggests that B lymphocytes play a role. Therefore, we explored B cell phenotypes in SSc patients using fluorescence cytometry and the multi-dimensional unsupervised analysis tool viSNE. We found that compared to healthy controls, SSc patients had significantly higher proportions of an autoreactive-prone B cell subset identified by low expression of CD21 (CD21lo). Previously, circulating CD21lo B cells were shown to express autoantibodies and were increased in other autoimmune diseases. When considering the clinical phenotypes of the SSc patients, we found that the frequency of CD21lo B cells was only increased in SSc patients with interstitial lung disease (ILD). ILD is a complication of SSc that is associated with increased morbidity and mortality. To our knowledge, this is the first time that a peripheral blood B cell subset has been identified in association with ILD in patients with a systemic autoimmune disease. We investigated the signaling properties of these anergic cells and found lower expression of Bruton’s tyrosine kinase (BTK) in CD21lo B cells compared to normal B cells. This was surprising, as BTK is thought to be overexpressed in autoimmunity, but may indicate that the anergic state is due in part to suppression of BTK-mediated signaling. Our data suggest that CD21lo B cells should be investigated for their role in SSc pathogenesis, and for their utility as a biomarker of ILD. In addition, these findings demonstrate a potential mechanism by which B cell depleting therapy may specifically benefit SSc patients with ILD.
Published: 2018
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28. Vasculitis in the intensive care unit

Author: Philip Seo and Erin M. Wilfong
Subjects: medicine.medical_specialty, Cyclophosphamide, business.industry, Systemic Vasculitis, MEDLINE, Glomerulonephritis, medicine.disease, Intensive care unit, law.invention, Airway Compromise, Intensive Care Units, Rheumatology, law, Intensive care, Immunology, Medicine, Humans, business, Intensive care medicine, Vasculitis, medicine.drug, Systemic vasculitis
Abstract: The systemic vasculitides are a diverse set of diseases linked by the presence of blood-vessel inflammation and are often associated with life-threatening or critical complications, including glomerulonephritis, diffuse alveolar haemorrhage, pulmonary arterial hypertension and airway compromise. The protean manifestations of the systemic vasculitides make them challenging to diagnose. Early recognition, however, is crucial to improving outcomes. This article serves as an introduction to these complex diseases, reviewing the manifestations of systemic vasculitis that may be encountered in an intensive care setting, and outlines an overall approach to their treatment.
Published: 2013

29. An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1

Author: Erin M. Wilfong, Yu Du, and Eric J. Toone
Subjects: Stereochemistry, Clinical Biochemistry, Fragment-based lead discovery, Pharmaceutical Science, Matrix Metalloproteinase Inhibitors, Hydroxamic Acids, Ligands, Biochemistry, Stromelysin 1, Article, chemistry.chemical_compound, Additive function, Drug Discovery, Humans, Binding site, Molecular Biology, Biphenyl, Hydroxamic acid, Binding Sites, Organic Chemistry, Biphenyl Compounds, Solvent, Biphenyl compound, chemistry, Drug Design, Molecular Medicine, Thermodynamics, Matrix Metalloproteinase 3
Abstract: Fragment based drug discovery remains a successful tool for pharmaceutical lead discovery. Although based upon the principle of thermodynamic additivity, the underlying thermodynamic basis is poorly understood. A thermodynamic additivity analysis was performed using stromelysin-1 and a series of biphenyl hydroxamate ligands identified through fragment additivity. Our studies suggest that, in this instance, additivity arises from enthalpic effects, while interaction entropies are unfavorable; this thermodynamic behavior is masked by proton transfer. Evaluation of the changes in constant pressure heat capacities during binding suggest that solvent exclusion from the binding site does not account for the dramatic affinity enhancements observed.
Published: 2011

30. A multidisciplinary approach to probing enthalpy-entropy compensation and the interfacial mobility model

Author: Erin M. Wilfong, Eric J. Toone, Thomas Kowatz, Terry L. Gustafson, Yu Du, Sivaramakrishnan Muthukrishnan, James H. Naismith, Christopher M. Hadad, Yuri Kogiso, and Amber Bowie
Subjects: Models, Molecular, Mobility model, Thermodynamics, Crystallography, X-Ray, Hydroxamic Acids, Ligands, Spectrum Analysis, Raman, Biochemistry, Catalysis, Article, symbols.namesake, Colloid and Surface Chemistry, Molecule, Protein activity, Computer Simulation, Spectroscopy, Binding Sites, Molecular Structure, Chemistry, Computational Biology, Isothermal titration calorimetry, Reduced mobility, Stereoisomerism, General Chemistry, Enthalpy–entropy compensation, symbols, Physical chemistry, Matrix Metalloproteinase 3, Raman spectroscopy
Abstract: In recent years, interfacial mobility has gained popularity as a model with which to rationalize both affinity in ligand binding and the often observed phenomenon of enthalpy-entropy compensation. While protein contraction and reduced mobility, as demonstrated by computational and NMR techniques respectively, have been correlated to entropies of binding for a variety of systems, to our knowledge, Raman difference spectroscopy has never been included in these analyses. Here, non-resonance Raman difference spectroscopy, isothermal titration calorimetry, and x-ray crystallography were utilized to correlate protein contraction, as demonstrated by an increase in protein interior packing and decreased residual protein movement, with trends of enthalpy-entropy compensation. These results are in accord with the interfacial mobility model, and lend additional credence to this view of protein activity.
Published: 2011

31. A single step purification for autolytic zinc proteinases

Author: Eric J. Toone, Ursala Locklear, and Erin M. Wilfong
Subjects: Autolysis (biology), Protein Folding, Clinical Biochemistry, Pharmaceutical Science, chemistry.chemical_element, Zinc, Biochemistry, Chromatography, Affinity, Article, Affinity chromatography, Catalytic Domain, Drug Discovery, Protein purification, Histidine, Molecular Biology, chemistry.chemical_classification, Oligopeptide, Metalloproteinase, Chromatography, Organic Chemistry, Imidazoles, Enzyme, chemistry, Molecular Medicine, Matrix Metalloproteinase 3, Autolysis, Oligopeptides
Abstract: We describe a novel single-step method for the purification of stromelysin-1 catalytic domain (SCD) via immobilized metal affinity chromatography under denaturing conditions that inhibit proteolytic activity followed by on-column refolding and spontaneous autolysis of the fusion peptide to yield pure, active stromelysin-1 catalytic domain. The methodology provides a general approach for the rapid purification of large quantities of zinc proteinases.
Published: 2009

32. Proinflammatory cytokines and ARDS pulmonary edema fluid induce CD40 on human mesenchymal stromal cells-A potential mechanism for immune modulation.

Author: Erin M Wilfong, Roxanne Croze, Xiaohui Fang, Matthew Schwede, Erene Niemi, Giselle Y López, Jae-Woo Lee, Mary C Nakamura, and Michael A Matthay
Subjects: Medicine, Science
Abstract: Human mesenchymal stem/stromal cells (hMSCs) are a promising therapy for acute respiratory distress syndrome (ARDS) and other inflammatory conditions. While considerable research has focused on paracrine effects and mitochondrial transfer that improve lung fluid balance, hMSCs are well known to have immunomodulatory properties as well. Some of these immunomodulatory properties have been related to previously reported paracrine effectors such as indoleamine-2,3-dioxygenase (IDO), but these effects cannot fully account for cell-contact dependent immunomodulation. Here, we report that CD40 is upregulated on hMSCs under the same conditions previously reported to induce IDO. Further, CD40 transcription is also upregulated on hMSCs by ARDS pulmonary edema fluid but not by hydrostatic pulmonary edema fluid. Transcription of CD40, as well as paracrine effectors TSG6 and PTGS2 remained significantly upregulated for at least 12 hours after withdrawal of cytokine stimulation. Finally, induction of this immune phenotype altered the transdifferentiation of hMSCs, one of their hallmark properties. CD40 may play an important role in the immunomodulatory effects of hMSCs in ARDS and inflammation.
Published: 2020
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32 results on '"Erin M. Wilfong"'

1. Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine

2. Jo-1 autoantigen-specific B cells are skewed towards distinct functional B cell subsets in anti-synthetase syndrome patients

3. Neurologic Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Hospitalized Patients During the First Year of the COVID-19 Pandemic

4. High-Dimensional Analysis Reveals Distinct Endotypes in Patients With Idiopathic Inflammatory Myopathies

5. Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease

6. Low Gut Microbial Diversity Augments Estrogen-Driven Pulmonary Fibrosis in Female-Predominant Interstitial Lung Disease

7. Risk Factors for Critical Coronavirus Disease 2019 and Mortality in Hospitalized Young Adults: An Analysis of the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Coronavirus Disease 2019 Registry

8. High-Throughput Detection of Autoantigen-Specific B Cells Among Distinct Functional Subsets in Autoimmune Donors

9. Risk factors for mortality and mortality rates in interstitial lung disease patients in the intensive care unit

10. Distinct CD3+CD14+T Cell-Monocytes are dynamic complexes that harbor HIV and are increased with glucose intolerance

11. CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

12. Intravenous immunoglobulin therapy for COVID-19 ARDS

13. Jo-1 autoantigen-specific B cells are skewed towards distinct functional B cell subsets in anti-synthetase syndrome patients

14. Single-Cell Profiling of the Antigen-Specific Response to BNT162b2 SARS-CoV-2 RNA Vaccine

15. High-dimensional analysis reveals abnormal B cell subsets associated with specific changes to circulating T and myeloid cell populations in patients with idiopathic inflammatory myopathies

16. Anti-tRNA synthetase syndrome interstitial lung disease: A single center experience

17. Systemic soluble Programmed Death-Ligand 1 levels in sarcoidosis subjects does not vary with disease progression

18. Severity of illness scores at presentation predict ICU admission and mortality in COVID-19

19. Myositis and Systemic Sclerosis Spectrum IPAF Patients Are More Likely to Respond Favorably to Immunosuppression

20. Interstitial Pneumonia With Autoimmune Features

21. Proinflammatory cytokines and ARDS pulmonary edema fluid induce CD40 on human mesenchymal stromal cells-A potential mechanism for immune modulation

22. Effect of a fluid bolus on cardiovascular collapse among critically ill adults undergoing tracheal intubation (PrePARE): a randomised controlled trial

23. 007. ANCA-ASSOCIATED INTERSTITIAL LUNG DISEASE: THE VANDERBILT EXPERIENCE

24. Reply

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26. Effects of bone marrow-derived mesenchymal stromal cells on gene expression in human alveolar type II cells exposed to TNF-α , IL-1β , and IFN-γ

27. Autoreactive-prone CD21lo B cells increased in scleroderma patients with interstitial lung disease

28. Vasculitis in the intensive care unit

29. An enthalpic basis of additivity in biphenyl hydroxamic acid ligands for stromelysin-1

30. A multidisciplinary approach to probing enthalpy-entropy compensation and the interfacial mobility model

31. A single step purification for autolytic zinc proteinases

32. Proinflammatory cytokines and ARDS pulmonary edema fluid induce CD40 on human mesenchymal stromal cells-A potential mechanism for immune modulation.

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32 results on '"Erin M. Wilfong"'

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