Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial

被引：31

作者：

Alotaibi, Faizah ^{[1
,2
]}

Alharbi, Naif Khalaf B. ^{[3
,4
]}

Rosen, Lindsey Y. ^{[5
]}

Asiri, Ayed M. ^{[6
]}

Assiri, Abdullah H. ^{[7
]}

Balkhy, Hanan ^{[8
]}

Al Jeraisy, Majed

Mandourah, Yasser ^{[9
]}

AlJohani, Sameera ^{[3
,4
,10
]}

Al Harbi, Shmeylan ^{[3
,4
,11
]}

Jokhdar, Hani A. Aziz M.

Deeb, Ahmad A. ^{[3
,4
]}

Memish, Ziad ^{[12
,13
]}

Jose, Jesna ^{[3
,4
]}

Ghazal, Sameeh

Al Faraj, Sarah A. ^{[9
]}

Al Mekhlafi, Ghaleb ^{[9
]}

Sherbeeni, Nisreen Murad ^{[9
]}

Elzein, Fatehi Elnour M. ^{[9
]}

AlMutairi, Badriah ^{[3
,4
]}

Al-Dawood, Abdulaziz L. ^{[3
,4
,15
]}

Abdullah, Mashan ^{[14
]}

Barhoumi, Tlili W. ^{[3
,4
]}

Alenazi, Mohammed ^{[3
,4
]}

Almasood, Abdulrahman M. ^{[3
,4
]}

Holland, Steven M.

Arabi, Yaseen ^{[3
,4
,15
,16
]}

Saudi Critical Care Trials Grp

机构：

[1] King Saud Bin Abdulaziz Univ Hlth Sci, Coll Sci & Hlth Profess, Riyadh, Saudi Arabia

[2] Minist Natl Guard Hlth Affairs, King Abdullah Int Med Res Ctr, Riyadh, Saudi Arabia

[3] King Abdullah Int Med Res Ctr, Riyadh, Saudi Arabia

[4] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia

[5] Natl Inst Allergy & Infect Dis NIAID, Natl Inst Hlth NIH, Div Intramural Res, Lab Clin Immunol & Microbiol, Bethesda, MD USA

[6] Prince Mohammed Bin Abdulaziz Hosp, Riyadh, Saudi Arabia

[7] Minist Hlth, Riyadh, Saudi Arabia

[8] WHO, Antimicrobial Resistance Div, Geneva, Switzerland

[9] Prince Sultan Mil Med City, Riyadh, Saudi Arabia

[10] King Abdul Aziz Med City, Minist Natl Guard Hlth Affairs, Dept Pathol & Lab Med, Riyadh, Saudi Arabia

[11] King Abdul Aziz Med City, Minist Natl Guard Hlth Affairs, Pharmaceut Care Dept, Riyadh, Saudi Arabia

[12] Alfaisal Univ, Prince Mohammed Bin Abdulaziz Hosp, Coll Med, Minist Hlth, Riyadh, Saudi Arabia

[13] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA USA

[14] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, Expt Med Dept, Riyadh, Saudi Arabia

[15] King Abdul Aziz Med City, Minist Natl Guard Hlth Affairs, Intens Care Dept, Riyadh, Saudi Arabia

[16] King Abdul Aziz Med City, Intens Care Dept, ICU 1425, POB 22490, Riyadh 11426, Saudi Arabia

来源：

INFLUENZA AND OTHER RESPIRATORY VIRUSES | 2023年 / 17卷 / 03期

关键词：

auto-abs; ICU; MERS; MIRACLE trial; Type I IFNs; MYASTHENIA-GRAVIS PATIENTS; ALPHA; ANTIBODIES; COV;

D O I：

10.1111/irv.13116

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

BackgroundType I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto-Abs) to type I IFNs were reported as a risk factor for life-threatening COVID-19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS). MethodsWe evaluated the prevalence of type I IFN auto-Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo-controlled clinical trial for treatment with IFN-beta 1b and lopinavir-ritonavir (MIRACLE trial). Samples were tested for type I IFN auto-Abs using a multiplex particle-based assay. ResultsAmong the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto-Abs for at least one subtype of type I IFNs. Auto-Abs positive patients were not different from auto-Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto-Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto-Abs negative patients. The effect of treatment with IFN-beta 1b and lopinavir-ritonavir did not significantly differ between the two groups. ConclusionThis study demonstrates the presence of type I IFN auto-Abs in hospitalized patients with MERS.

引用

页数：8

共 29 条

[1] SARS-CoV-2, the other face to SARS-CoV and MERS-CoV: Future predictions [J].

Abdelghany, T. M. ;

Ganash, Magdah ;

Bakri, Marwah M. ;

Qanash, Husam ;

Al-Rajhi, Aisha M. H. ;

Elhussieny, Nadeem, I .

BIOMEDICAL JOURNAL, 2021, 44 (01) :86-93

[2] Neutralizing type-I interferon autoantibodies are associated with delayed viral clearance and intensive care unit admission in patients with COVID-19 [J].

Abers, Michael S. ;

Rosen, Lindsey B. ;

Delmonte, Ottavia M. ;

Shaw, Elana ;

Bastard, Paul ;

Imberti, Luisa ;

Quaresima, Virginia ;

Biondi, Andrea ;

Bonfanti, Paolo ;

Castagnoli, Riccardo ;

Casanova, Jean-Laurent ;

Su, Helen C. ;

Notarangelo, Luigi D. ;

Holland, Steven M. ;

Lionakis, Michail S. .

IMMUNOLOGY AND CELL BIOLOGY, 2021, 99 (09) :917-921

[3]

Almasaud A, 2020, METHODS MOL BIOL, V2099, P117, DOI 10.1007/978-1-0716-0211-9_10

[4] Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome [J].

Arabi, Yaseen M. ;

Asiri, Ayed Y. ;

Assiri, Abdullah M. ;

Balkhy, Hanan H. ;

Al Bshabshe, Ali ;

Al Jeraisy, Majed ;

Mandourah, Yasser ;

Azzam, Mohamed H. A. ;

Bin Eshaq, Abdulhadi M. ;

Al Johani, Sameera ;

Al Harbi, Shmeylan ;

Jokhdar, Hani A. A. ;

Deeb, Ahmad M. ;

Memish, Ziad A. ;

Jose, Jesna ;

Ghazal, Sameeh ;

Al Faraj, Sarah ;

Al Mekhlafi, Ghaleb A. ;

Sherbeeni, Nisreen M. ;

Elzein, Fatehi E. ;

Al-Hameed, Fahad ;

Al Saedi, Asim ;

Alharbi, Naif K. ;

Fowler, Robert A. ;

Hayden, Frederick G. ;

Al-Dawood, Abdulaziz ;

Abdelzaher, Mohamed ;

Bajhmom, Wail ;

AlMutairi, Badriah M. ;

Hussein, Mohamed A. ;

Alothman, Adel .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (17) :1645-1656

[5] Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-β1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial [J].

Arabi, Yaseen M. ;

Asiri, Ayed Y. ;

Assiri, Abdullah M. ;

Aziz Jokhdar, Hani A. ;

Alothman, Adel ;

Balkhy, Hanan H. ;

AlJohani, Sameera ;

Al Harbi, Shmeylan ;

Kojan, Suleiman ;

Al Jeraisy, Majed ;

Deeb, Ahmad M. ;

Memish, Ziad A. ;

Ghazal, Sameeh ;

Al Faraj, Sarah ;

Al-Hameed, Fahad ;

AlSaedi, Asim ;

Mandourah, Yasser ;

Al Mekhlafi, Ghaleb A. ;

Sherbeeni, Nisreen Murad ;

Elzein, Fatehi Elnour ;

Almotairi, Abdullah ;

Al Bshabshe, Ali ;

Kharaba, Ayman ;

Jose, Jesna ;

Al Harthy, Abdulrahman ;

Al Sulaiman, Mohammed ;

Mady, Ahmed ;

Fowler, Robert A. ;

Hayden, Frederick G. ;

Al-Dawood, Abdulaziz ;

Abdelzaher, Mohamed ;

Bajhmom, Wail ;

Hussein, Mohamed A. .

TRIALS, 2020, 21 (01)

[6] Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial [J].

Arabi, Yaseen M. ;

Alothman, Adel ;

Balkhy, Hanan H. ;

Al-Dawood, Abdulaziz ;

AlJohani, Sameera ;

Al Harbi, Shmeylan ;

Kojan, Suleiman ;

Al Jeraisy, Majed ;

Deeb, Ahmad M. ;

Assiri, Abdullah M. ;

Al-Hameed, Fahad ;

AlSaedi, Asim ;

Mandourah, Yasser ;

Almekhlafi, Ghaleb A. ;

Sherbeeni, Nisreen Murad ;

Elzein, Fatehi Elnour ;

Memon, Javed ;

Taha, Yusri ;

Almotairi, Abdullah ;

Maghrabi, Khalid A. ;

Qushmaq, Ismael ;

Al Bshabshe, Ali ;

Kharaba, Ayman ;

Shalhoub, Sarah ;

Jose, Jesna ;

Fowler, Robert A. ;

Hayden, Frederick G. ;

Hussein, Mohamed A. .

TRIALS, 2018, 19

[7] Risk factors for severity and mortality in patients with MERS-CoV: Analysis of publicly available data from Saudi Arabia [J].

Banik, Gouri Rani ;

Alqahtani, Amani Salem ;

Booy, Robert ;

Rashid, Harunor .

VIROLOGICA SINICA, 2016, 31 (01) :81-84

[8] Autoantibodies neutralizing type I IFNs are present in ∼4% of uninfected individuals over 70 years old and account for ∼20% of COVID-19 deaths [J].

Bastard, Paul ;

Gervais, Adrian ;

Le Voyer, Tom ;

Rosain, Jeremie ;

Philippot, Quentin ;

Manry, Jeremy ;

Michailidis, Eleftherios ;

Hoffmann, Hans-Heinrich ;

Eto, Shohei ;

Garcia-Prat, Marina ;

Bizien, Lucy ;

Parra-Martinez, Alba ;

Yang, Rui ;

Haljasmagi, Liis ;

Migaud, Melanie ;

Sarekannu, Karita ;

Maslovskaja, Julia ;

de Prost, Nicolas ;

Tandjaoui-Lambiotte, Yacine ;

Luyt, Charles-Edouard ;

Amador-Borrero, Blanca ;

Gaudet, Alexandre ;

Poissy, Julien ;

Morel, Pascal ;

Richard, Pascale ;

Cognasse, Fabrice ;

Troya, Jesus ;

Trouillet-Assant, Sophie ;

Belot, Alexandre ;

Saker, Kahina ;

Garcon, Pierre ;

Riviere, Jacques G. ;

Lagier, Jean-Christophe ;

Gentile, Stephanie ;

Rosen, Lindsey B. ;

Shaw, Elana ;

Morio, Tomohiro ;

Tanaka, Junko ;

Dalmau, David ;

Tharaux, Pierre-Louis ;

Sene, Damien ;

Stepanian, Alain ;

Megarbane, Bruno ;

Triantafyllia, Vasiliki ;

Fekkar, Arnaud ;

Heath, James R. ;

Franco, Jose Luis ;

Anaya, Juan-Manuel ;

Sole-Violan, Jordi ;

Imberti, Luisa .

SCIENCE IMMUNOLOGY, 2021, 6 (62)

[9] Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1 [J].

Bastard, Paul ;

Orlova, Elizaveta ;

Sozaeva, Leila ;

Levy, Romain ;

James, Alyssa ;

Schmitt, Monica M. ;

Ochoa, Sebastian ;

Kareva, Maria ;

Rodina, Yulia ;

Gervais, Adrian ;

Le Voyer, Tom ;

Rosain, Jeremie ;

Philippot, Quentin ;

Neehus, Anna-Lena ;

Shaw, Elana ;

Migaud, Melanie ;

Bizien, Lucy ;

Ekwall, Olov ;

Berg, Stefan ;

Beccuti, Guglielmo ;

Ghizzoni, Lucia ;

Thiriez, Gerard ;

Pavot, Arthur ;

Goujard, Cecile ;

Fremond, Marie-Louise ;

Carter, Edwin ;

Rothenbuhler, Anya ;

Linglart, Agnes ;

Mignot, Brigite ;

Comte, Aurelie ;

Cheikh, Nathalie ;

Hermine, Olivier ;

Breivik, Lars ;

Husebye, Eystein S. ;

Humbert, Sebastien ;

Rohrlich, Pierre ;

Coaquette, Alain ;

Vuoto, Fanny ;

Faure, Karine ;

Mahlaoui, Nizar ;

Kotnik, Primoz ;

Battelino, Tadej ;

Podkrajsek, Katarina Trebusak ;

Kisand, Kai ;

Ferre, Elise M. N. ;

DiMaggio, Thomas ;

Rosen, Lindsey B. ;

Burbelo, Peter D. ;

McIntyre, Martin ;

Kann, Nelli Y. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2021, 218 (07)

[10] Autoantibodies against type I IFNs in patients with life-threatening COVID-19 [J].

Bastard, Paul ;

Rosen, Lindsey B. ;

Zhang, Qian ;

Michailidis, Eleftherios ;

Hoffmann, Hans-Heinrich ;

Zhang, Yu ;

Dorgham, Karim ;

Philippot, Quentin ;

Rosain, Jeremie ;

Beziat, Vivien ;

Manry, Jeremy ;

Shaw, Elana ;

Haljasmagi, Liis ;

Peterson, Part ;

Lorenzo, Lazaro ;

Bizien, Lucy ;

Trouillet-Assant, Sophie ;

Dobbs, Kerry ;

de Jesus, Adriana Almeida ;

Belot, Alexandre ;

Kallaste, Anne ;

Catherinot, Emilie ;

Tandjaoui-Lambiotte, Yacine ;

Le Pen, Jeremie ;

Kerner, Gaspard ;

Bigio, Benedetta ;

Seeleuthner, Yoann ;

Yang, Rui ;

Bolze, Alexandre ;

Spaan, Andras N. ;

Delmonte, Ottavia M. ;

Abers, Michael S. ;

Aiuti, Alessandro ;

Casari, Giorgio ;

Lampasona, Vito ;

Piemonti, Lorenzo ;

Ciceri, Fabio ;

Bilguvar, Kaya ;

Lifton, Richard P. ;

Vasse, Marc ;

Smadja, David M. ;

Migaud, Melanie ;

Hadjadj, Jerome ;

Terrier, Benjamin ;

Duffy, Darragh ;

Quintana-Murci, Lluis ;

van de Beek, Diederik ;

Roussel, Lucie ;

Vinh, Donald C. ;

Tangye, Stuart G. .

SCIENCE, 2020, 370 (6515) :423-+

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