@article {904, title = {Autoantibodies against type I IFNs in patients with life-threatening COVID-19.}, journal = {Science}, volume = {370}, year = {2020}, month = {2020 10 23}, abstract = {

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6\% of women and 12.5\% of men.

}, keywords = {Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing, Asymptomatic Infections, Autoantibodies, Betacoronavirus, Case-Control Studies, Coronavirus Infections, COVID-19, Critical Illness, Female, Humans, Immunoglobulin G, Interferon alpha-2, Interferon Type I, Male, Middle Aged, Pandemics, Pneumonia, Viral, SARS-CoV-2}, issn = {1095-9203}, doi = {10.1126/science.abd4585}, author = {Bastard, Paul and Rosen, Lindsey B and Zhang, Qian and Michailidis, Eleftherios and Hoffmann, Hans-Heinrich and Zhang, Yu and Dorgham, Karim and Philippot, Quentin and Rosain, J{\'e}r{\'e}mie and B{\'e}ziat, Vivien and Manry, Jeremy and Shaw, Elana and Haljasm{\"a}gi, Liis and Peterson, P{\"a}rt and Lorenzo, Lazaro and Bizien, Lucy and Trouillet-Assant, Sophie and Dobbs, Kerry and de Jesus, Adriana Almeida and Belot, Alexandre and Kallaste, Anne and Catherinot, Emilie and Tandjaoui-Lambiotte, Yacine and Le Pen, J{\'e}r{\'e}mie and Kerner, Gaspard and Bigio, Benedetta and Seeleuthner, Yoann and Yang, Rui and Bolze, Alexandre and Spaan, Andr{\'a}s N and Delmonte, Ottavia M and Abers, Michael S and Aiuti, Alessandro and Casari, Giorgio and Lampasona, Vito and Piemonti, Lorenzo and Ciceri, Fabio and Bilguvar, Kaya and Lifton, Richard P and Vasse, Marc and Smadja, David M and Migaud, M{\'e}lanie and Hadjadj, J{\'e}rome and Terrier, Benjamin and Duffy, Darragh and Quintana-Murci, Lluis and van de Beek, Diederik and Roussel, Lucie and Vinh, Donald C and Tangye, Stuart G and Haerynck, Filomeen and Dalmau, David and Martinez-Picado, Javier and Brodin, Petter and Nussenzweig, Michel C and Boisson-Dupuis, St{\'e}phanie and Rodr{\'\i}guez-Gallego, Carlos and Vogt, Guillaume and Mogensen, Trine H and Oler, Andrew J and Gu, Jingwen and Burbelo, Peter D and Cohen, Jeffrey I and Biondi, Andrea and Bettini, Laura Rachele and D{\textquoteright}Angio, Mariella and Bonfanti, Paolo and Rossignol, Patrick and Mayaux, Julien and Rieux-Laucat, Fr{\'e}d{\'e}ric and Husebye, Eystein S and Fusco, Francesca and Ursini, Matilde Valeria and Imberti, Luisa and Sottini, Alessandra and Paghera, Simone and Quiros-Roldan, Eugenia and Rossi, Camillo and Castagnoli, Riccardo and Montagna, Daniela and Licari, Amelia and Marseglia, Gian Luigi and Duval, Xavier and Ghosn, Jade and Tsang, John S and Goldbach-Mansky, Raphaela and Kisand, Kai and Lionakis, Michail S and Puel, Anne and Zhang, Shen-Ying and Holland, Steven M and Gorochov, Guy and Jouanguy, Emmanuelle and Rice, Charles M and Cobat, Aurelie and Notarangelo, Luigi D and Abel, Laurent and Su, Helen C and Casanova, Jean-Laurent} } @article {731, title = {A combined immunodeficiency with severe infections, inflammation, and allergy caused by ARPC1B deficiency.}, journal = {J Allergy Clin Immunol}, volume = {143}, year = {2019}, month = {2019 Jun}, pages = {2296-2299}, issn = {1097-6825}, doi = {10.1016/j.jaci.2019.02.003}, author = {Volpi, Stefano and Cicalese, Maria Pia and Tuijnenburg, Paul and Tool, Anton T J and Cuadrado, Eloy and Abu-Halaweh, Marwan and Ahanchian, Hamid and Alzyoud, Raed and Akdemir, Zeynep Coban and Barzaghi, Federica and Blank, Alexander and Boisson, Bertrand and Bottino, Cristina and Brigida, Immacolata and Caorsi, Roberta and Casanova, Jean-Laurent and Chiesa, Sabrina and Chinn, Ivan Kingyue and D{\"u}ckers, Gregor and Enders, Anselm and Erichsen, Hans Christian and Forbes, Lisa R and Gambin, Tomasz and Gattorno, Marco and Karimiani, Ehsan Ghayoor and Giliani, Silvia and Gold, Michael S and Jacobsen, Eva-Maria and Jansen, Machiel H and King, Jovanka R and Laxer, Ronald M and Lupski, James R and Mace, Emily and Marcenaro, Stefania and Maroofian, Reza and Meijer, Alexander B and Niehues, Tim and Notarangelo, Luigi D and Orange, Jordan and Pannicke, Ulrich and Pearson, Chris and Picco, Paolo and Quinn, Patrick J and Schulz, Ansgar and Seeborg, Filiz and Stray-Pedersen, Asbj{\o}rg and Tawamie, Hasan and van Leeuwen, Ester M M and Aiuti, Alessandro and Yeung, Rae and Schwarz, Klaus and Kuijpers, Taco W} } @article {27, title = {Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders.}, journal = {J Allergy Clin Immunol}, volume = {139}, year = {2017}, month = {2017 Jan}, pages = {232-245}, abstract = {

BACKGROUND: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions.

OBJECTIVE: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs.

METHODS: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping.

RESULTS: A likely molecular diagnosis was achieved in 110 (40\%) unrelated probands. Clinical diagnosis was revised in about half (60/110) and management was directly altered in nearly a quarter (26/110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30~Kb that would not have been detected with conventional diagnostic CNV arrays.

CONCLUSION: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.

}, keywords = {Adolescent, Adult, Aged, Child, Child, Preschool, DNA Copy Number Variations, Female, Genomics, High-Throughput Nucleotide Sequencing, Humans, Immunologic Deficiency Syndromes, Infant, Male, Middle Aged, Young Adult}, issn = {1097-6825}, doi = {10.1016/j.jaci.2016.05.042}, author = {Stray-Pedersen, Asbj{\o}rg and Sorte, Hanne S{\o}rmo and Samarakoon, Pubudu and Gambin, Tomasz and Chinn, Ivan K and Coban Akdemir, Zeynep H and Erichsen, Hans Christian and Forbes, Lisa R and Gu, Shen and Yuan, Bo and Jhangiani, Shalini N and Muzny, Donna M and R{\o}dningen, Olaug Kristin and Sheng, Ying and Nicholas, Sarah K and Noroski, Lenora M and Seeborg, Filiz O and Davis, Carla M and Canter, Debra L and Mace, Emily M and Vece, Timothy J and Allen, Carl E and Abhyankar, Harshal A and Boone, Philip M and Beck, Christine R and Wiszniewski, Wojciech and Fevang, B{\o}rre and Aukrust, P{\r a}l and Tj{\o}nnfjord, Geir E and Gedde-Dahl, Tobias and Hjorth-Hansen, Henrik and Dybedal, Ingunn and Nord{\o}y, Ingvild and J{\o}rgensen, Silje F and Abrahamsen, Tore G and {\O}verland, Torstein and Bechensteen, Anne Grete and Skogen, Vegard and Osnes, Liv T N and Kulseth, Mari Ann and Prescott, Trine E and Rustad, Cecilie F and Heimdal, Ketil R and Belmont, John W and Rider, Nicholas L and Chinen, Javier and Cao, Tram N and Smith, Eric A and Caldirola, Maria Soledad and Bezrodnik, Liliana and Lugo Reyes, Saul Oswaldo and Espinosa Rosales, Francisco J and Guerrero-Cursaru, Nina Denisse and Pedroza, Luis Alberto and Poli, Cecilia M and Franco, Jose L and Trujillo Vargas, Claudia M and Aldave Becerra, Juan Carlos and Wright, Nicola and Issekutz, Thomas B and Issekutz, Andrew C and Abbott, Jordan and Caldwell, Jason W and Bayer, Diana K and Chan, Alice Y and Aiuti, Alessandro and Cancrini, Caterina and Holmberg, Eva and West, Christina and Burstedt, Magnus and Karaca, Ender and Yesil, G{\"o}zde and Artac, Hasibe and Bayram, Yavuz and Atik, Mehmed Musa and Eldomery, Mohammad K and Ehlayel, Mohammad S and Jolles, Stephen and Flat{\o}, Berit and Bertuch, Alison A and Hanson, I Celine and Zhang, Victor W and Wong, Lee-Jun and Hu, Jianhong and Walkiewicz, Magdalena and Yang, Yaping and Eng, Christine M and Boerwinkle, Eric and Gibbs, Richard A and Shearer, William T and Lyle, Robert and Orange, Jordan S and Lupski, James R} }