Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee

Stuart G Tangye, Waleed Al-Herz, Aziz Bousfiha, Talal Chatila, Charlotte Cunningham-Rundles, Amos Etzioni, Jose Luis Franco, Steven M Holland, Christoph Klein, Tomohiro Morio, Hans D Ochs, Eric Oksenhendler, Capucine Picard, Jennifer Puck, Troy R Torgerson, Jean-Laurent Casanova, Kathleen E Sullivan, Stuart G Tangye, Waleed Al-Herz, Aziz Bousfiha, Talal Chatila, Charlotte Cunningham-Rundles, Amos Etzioni, Jose Luis Franco, Steven M Holland, Christoph Klein, Tomohiro Morio, Hans D Ochs, Eric Oksenhendler, Capucine Picard, Jennifer Puck, Troy R Torgerson, Jean-Laurent Casanova, Kathleen E Sullivan

Abstract

We report the updated classification of Inborn Errors of Immunity/Primary Immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee. This report documents the key clinical and laboratory features of 430 inborn errors of immunity, including 64 gene defects that have either been discovered in the past 2 years since the previous update (published January 2018) or were characterized earlier but have since been confirmed or expanded upon in subsequent studies. The application of next-generation sequencing continues to expedite the rapid identification of novel gene defects, rare or common; broaden the immunological and clinical phenotypes of conditions arising from known gene defects and even known variants; and implement gene-specific therapies. These advances are contributing to greater understanding of the molecular, cellular, and immunological mechanisms of disease, thereby enhancing immunological knowledge while improving the management of patients and their families. This report serves as a valuable resource for the molecular diagnosis of individuals with heritable immunological disorders and also for the scientific dissection of cellular and molecular mechanisms underlying inborn errors of immunity and related human diseases.

Keywords: IUIS; autoinflammatory disorders; immune dysregulation; inborn errors of immunity; next-generation sequencing; primary immune deficiency.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Rate of discovery of novel inborn errors of immunity: 1983–2019. a The number of genetic defects underlying monogenic immune disorders as reported by the IUIS/WHO committee in the indicated year. b The number of pathogenic gene variants listed in each table by the IUIS committee. Report published in 2017, and the number of new genes for each table contained in this report (red bars). The numbers in each column correspond to the number of genes reported in the 2017 IUIS update (blue bars) [1, 2], the number of new genes for each table contained in this report (red bars), and the total number of genes for each table. Note: only data for Tables 1, 2, 3, 4, 5, 6, 7, and 8 are shown, because Table 9 (bone marrow failure) is a new addition to the current report.

References

    1. Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, et al. International Union of Immunological Societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018;38(1):96–128. doi: 10.1007/s10875-017-0464-9.
    1. Bousfiha A, Jeddane L, Picard C, Ailal F, Bobby Gaspar H, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary Immunodeficiencies. J Clin Immunol. 2018;38(1):129–143. doi: 10.1007/s10875-017-0465-8.
    1. Casanova JL, Abel L. Human genetics of infectious diseases: unique insights into immunological redundancy. Semin Immunol. 2018;36:1–12. doi: 10.1016/j.smim.2017.12.008.
    1. Fischer A, Rausell A. What do primary immunodeficiencies tell us about the essentiality/redundancy of immune responses? Semin Immunol. 2018;36:13–16. doi: 10.1016/j.smim.2017.12.001.
    1. Zhang SY, Jouanguy E, Zhang Q, Abel L, Puel A, Casanova JL. Human inborn errors of immunity to infection affecting cells other than leukocytes: from the immune system to the whole organism. Curr Opin Immunol. 2019;59:88–100. doi: 10.1016/j.coi.2019.03.008.
    1. Bucciol G, Moens L, Bosch B, Bossuyt X, Casanova JL, Puel A, et al. Lessons learned from the study of human inborn errors of innate immunity. J Allergy Clin Immunol. 2019;143(2):507–527. doi: 10.1016/j.jaci.2018.07.013.
    1. Meyts I, Bosch B, Bolze A, Boisson B, Itan Y, Belkadi A, et al. Exome and genome sequencing for inborn errors of immunity. J Allergy Clin Immunol. 2016;138(4):957–969. doi: 10.1016/j.jaci.2016.08.003.
    1. Picard C, Fischer A. Contribution of high-throughput DNA sequencing to the study of primary immunodeficiencies. Eur J Immunol. 2014;44(10):2854–2861. doi: 10.1002/eji.201444669.
    1. Zhang Q, Frange P, Blanche S, Casanova JL. Pathogenesis of infections in HIV-infected individuals: insights from primary immunodeficiencies. Curr Opin Immunol. 2017;48:122–133. doi: 10.1016/j.coi.2017.09.002.
    1. Kerner G, Ramirez-Alejo N, Seeleuthner Y, Yang R, Ogishi M, Cobat A, et al. Homozygosity for TYK2 P1104A underlies tuberculosis in about 1% of patients in a cohort of European ancestry. Proc Natl Acad Sci U S A. 2019;116(21):10430–10434. doi: 10.1073/pnas.1903561116.
    1. Leiding JW, Forbes LR. Mechanism-based precision therapy for the treatment of primary immunodeficiency and primary Immunodysregulatory diseases. J Allergy Clin Immunol Pract. 2019;7(3):761–773. doi: 10.1016/j.jaip.2018.12.017.
    1. Conley ME, Dobbs AK, Farmer DM, Kilic S, Paris K, Grigoriadou S, et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol. 2009;27:199–227. doi: 10.1146/annurev.immunol.021908.132649.
    1. Fischer A, Rausell A. Primary immunodeficiencies suggest redundancy within the human immune system. Sci Immunol. 2016;1(6). 10.1126/sciimmunol.aah5861.
    1. Gayko U, Fung M, Clow F, Sun S, Faust E, Price S, et al. Development of the Bruton's tyrosine kinase inhibitor ibrutinib for B cell malignancies. Ann N Y Acad Sci. 2015;1358:82–94. doi: 10.1111/nyas.12878.
    1. Ma CS, Tangye SG. Flow Cytometric-based analysis of defects in lymphocyte differentiation and function due to inborn errors of immunity. Front Immunol. 2019;10:2108. doi: 10.3389/fimmu.2019.02108.
    1. Bruton OC. Agammaglobulinemia Pediatrics. 1952;9(6):722–728.
    1. Casanova JL, Conley ME, Seligman SJ, Abel L, Notarangelo LD. Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies. J Exp Med. 2014;211(11):2137–2149. doi: 10.1084/jem.20140520.
    1. Byun M, Abhyankar A, Lelarge V, Plancoulaine S, Palanduz A, Telhan L, et al. Whole-exome sequencing-based discovery of STIM1 deficiency in a child with fatal classic Kaposi sarcoma. J Exp Med. 2010;207(11):2307–2312. doi: 10.1084/jem.20101597.
    1. Beziat V, Li J, Lin JX, Ma CS, Li P, Bousfiha A, et al. A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity. Sci Immunol. 2018;3(24). 10.1126/sciimmunol.aat4956.
    1. Frey-Jakobs S, Hartberger JM, Fliegauf M, Bossen C, Wehmeyer ML, Neubauer JC, et al. ZNF341 controls STAT3 expression and thereby immunocompetence. Sci Immunol. 2018;3(24). 10.1126/sciimmunol.aat4941.
    1. Shahin T, Aschenbrenner D, Cagdas D, Bal SK, Conde CD, Garncarz W, et al. Selective loss of function variants in IL6ST cause hyper-IgE syndrome with distinct impairments of T-cell phenotype and function. Haematologica. 2019;104(3):609–621. doi: 10.3324/haematol.2018.194233.
    1. Schwerd T, Twigg SRF, Aschenbrenner D, Manrique S, Miller KA, Taylor IB, et al. A biallelic mutation in IL6ST encoding the GP130 co-receptor causes immunodeficiency and craniosynostosis. J Exp Med. 2017;214(9):2547–2562. doi: 10.1084/jem.20161810.
    1. Spencer S, Kostel Bal S, Egner W, Lango Allen H, Raza SI, Ma CA, et al. Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses. J Exp Med. 2019;216(9):1986–1998. doi: 10.1084/jem.20190344.
    1. Nahum A, Sharfe N, Broides A, Dadi H, Naghdi Z, Mandola AB, et al. Defining the biological responses of IL-6 by the study of a novel IL-6 receptor chain (IL6R) immunodeficiency. J Allergy Clin Immunol. 2019. 10.1016/j.jaci.2019.11.015.
    1. Ma CA, Stinson JR, Zhang Y, Abbott JK, Weinreich MA, Hauk PJ, et al. Germline hypomorphic CARD11 mutations in severe atopic disease. Nat Genet. 2017;49(8):1192–1201. doi: 10.1038/ng.3898.
    1. Dorjbal B, Stinson JR, Ma CA, Weinreich MA, Miraghazadeh B, Hartberger JM, et al. Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease. J Allergy Clin Immunol. 2019;143(4):1482–1495. doi: 10.1016/j.jaci.2018.08.013.
    1. Klammt J, Neumann D, Gevers EF, Andrew SF, Schwartz ID, Rockstroh D, et al. Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation. Nat Commun. 2018;9(1):2105. doi: 10.1038/s41467-018-04521-0.
    1. Lu HY, Bauman BM, Arjunaraja S, Dorjbal B, Milner JD, Snow AL, et al. The CBM-opathies-A rapidly expanding Spectrum of human inborn errors of immunity caused by mutations in the CARD11-BCL10-MALT1 complex. Front Immunol. 2018;9:2078. doi: 10.3389/fimmu.2018.02078.
    1. Nadeau K, Hwa V, Rosenfeld RG. STAT5b deficiency: an unsuspected cause of growth failure, immunodeficiency, and severe pulmonary disease. J Pediatr. 2011;158(5):701–708. doi: 10.1016/j.jpeds.2010.12.042.
    1. Boisson B, Wang YD, Bosompem A, Ma CS, Lim A, Kochetkov T, et al. A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(−) B cells. J Clin Invest. 2013;123(11):4781–4785. doi: 10.1172/JCI71927.
    1. Ben-Ali M, Yang J, Chan KW, Ben-Mustapha I, Mekki N, Benabdesselem C, et al. Homozygous transcription factor 3 gene (TCF3) mutation is associated with severe hypogammaglobulinemia and B-cell acute lymphoblastic leukemia. J Allergy Clin Immunol. 2017;140(4):1191–4 e4. doi: 10.1016/j.jaci.2017.04.037.
    1. Qureshi S, Sheikh MDA, Qamar FN. Autosomal recessive Agammaglobulinemia - first case with a novel TCF3 mutation from Pakistan. Clin Immunol. 2019;198:100–101. doi: 10.1016/j.clim.2018.07.016.
    1. Cardinez C, Miraghazadeh B, Tanita K, da Silva E, Hoshino A, Okada S, et al. Gain-of-function IKBKB mutation causes human combined immune deficiency. J Exp Med. 2018;215(11):2715–2724. doi: 10.1084/jem.20180639.
    1. Pannicke U, Baumann B, Fuchs S, Henneke P, Rensing-Ehl A, Rizzi M, et al. Deficiency of innate and acquired immunity caused by an IKBKB mutation. N Engl J Med. 2013;369(26):2504–2514. doi: 10.1056/NEJMoa1309199.
    1. Sogkas G, Fedchenko M, Dhingra A, Jablonka A, Schmidt RE, Atschekzei F. Primary immunodeficiency disorder caused by phosphoinositide 3-kinase delta deficiency. J Allergy Clin Immunol. 2018;142(5):1650–1653. doi: 10.1016/j.jaci.2018.06.039.
    1. Cohen SB, Bainter W, Johnson JL, Lin TY, Wong JCY, Wallace JG, et al. Human primary immunodeficiency caused by expression of a kinase-dead p110delta mutant. J Allergy Clin Immunol. 2019;143(2):797–9 e2. doi: 10.1016/j.jaci.2018.10.005.
    1. Tangye SG, Bier J, Lau A, Nguyen T, Uzel G, Deenick EK. Immune Dysregulation and disease pathogenesis due to activating mutations in PIK3CD-the Goldilocks' effect. J Clin Immunol. 2019;39(2):148–158. doi: 10.1007/s10875-019-00612-9.
    1. Boutboul D, Kuehn HS, Van de Wyngaert Z, Niemela JE, Callebaut I, Stoddard J, et al. Dominant-negative IKZF1 mutations cause a T, B, and myeloid cell combined immunodeficiency. J Clin Invest. 2018;128(7):3071–3087. doi: 10.1172/JCI98164.
    1. Kuehn HS, Boisson B, Cunningham-Rundles C, Reichenbach J, Stray-Pedersen A, Gelfand EW, et al. Loss of B cells in patients with heterozygous mutations in IKAROS. N Engl J Med. 2016;374(11):1032–1043. doi: 10.1056/NEJMoa1512234.
    1. Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC, et al. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood. 2016;127(25):3154–3164. doi: 10.1182/blood-2015-11-679902.
    1. Alkhairy OK, Rezaei N, Graham RR, Abolhassani H, Borte S, Hultenby K, et al. RAC2 loss-of-function mutation in 2 siblings with characteristics of common variable immunodeficiency. J Allergy Clin Immunol. 2015;135(5):1380–4 e1-5. doi: 10.1016/j.jaci.2014.10.039.
    1. Hsu AP, Donko A, Arrington ME, Swamydas M, Fink D, Das A, et al. Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects. Blood. 2019;133(18):1977–1988. doi: 10.1182/blood-2018-11-886028.
    1. Lougaris V, Chou J, Beano A, Wallace JG, Baronio M, Gazzurelli L, et al. A monoallelic activating mutation in RAC2 resulting in a combined immunodeficiency. J Allergy Clin Immunol. 2019;143(4):1649–1653. doi: 10.1016/j.jaci.2019.01.001.
    1. Sharapova SO, Haapaniemi E, Sakovich IS, Kostyuchenko LV, Donko A, Dulau-Florea A, et al. Heterozygous activating mutation in RAC2 causes infantile-onset combined immunodeficiency with susceptibility to viral infections. Clin Immunol. 2019;205:1–5. doi: 10.1016/j.clim.2019.05.003.
    1. Smits BM, Lelieveld PHC, Ververs FA, Turkenburg M, de Koning C, van Dijk M, et al. A dominant activating RAC2 variant associated with immunodeficiency and pulmonary disease. Clin Immunol. 2019;108248. 10.1016/j.clim.2019.108248.
    1. Hernandez N, Melki I, Jing H, Habib T, Huang SSY, Danielson J, et al. Life-threatening influenza pneumonitis in a child with inherited IRF9 deficiency. J Exp Med. 2018;215(10):2567–2585. doi: 10.1084/jem.20180628.
    1. Belkaya S, Michailidis E, Korol CB, Kabbani M, Cobat A, Bastard P, et al. Inherited IL-18BP deficiency in human fulminant viral hepatitis. J Exp Med. 2019;216(8):1777–1790. doi: 10.1084/jem.20190669.
    1. Serwas NK, Hoeger B, Ardy RC, Stulz SV, Sui Z, Memaran N, et al. Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis. Nat Commun. 2019;10(1):3106. doi: 10.1038/s41467-019-10812-x.
    1. Lo B, Zhang K, Lu W, Zheng L, Zhang Q, Kanellopoulou C, et al. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science. 2015;349(6246):436–440. doi: 10.1126/science.aaa1663.
    1. Schwab C, Gabrysch A, Olbrich P, Patino V, Warnatz K, Wolff D, et al. Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects. J Allergy Clin Immunol. 2018;142(6):1932–1946. doi: 10.1016/j.jaci.2018.02.055.
    1. Martinez-Barricarte R, Markle JG, Ma CS, Deenick EK, Ramirez-Alejo N, Mele F, et al. Human IFN-gamma immunity to mycobacteria is governed by both IL-12 and IL-23. Sci Immunol. 2018;3(30). 10.1126/sciimmunol.aau6759.
    1. Kong XF, Martinez-Barricarte R, Kennedy J, Mele F, Lazarov T, Deenick EK, et al. Disruption of an antimycobacterial circuit between dendritic and helper T cells in human SPPL2a deficiency. Nat Immunol. 2018;19(9):973–985. doi: 10.1038/s41590-018-0178-z.
    1. Roussel L, Landekic M, Golizeh M, Gavino C, Zhong MC, Chen J, et al. Loss of human ICOSL results in combined immunodeficiency. J Exp Med. 2018;215(12):3151–3164. doi: 10.1084/jem.20180668.
    1. Conde CD, Petronczki OY, Baris S, Willmann KL, Girardi E, Salzer E, et al. Polymerase delta deficiency causes syndromic immunodeficiency with replicative stress. J Clin Invest. 2019;129(10):4194–4206. doi: 10.1172/JCI128903.
    1. Cui Y, Keles S, Charbonnier LM, Jule AM, Henderson L, Celik SC, et al. Combined immunodeficiency due to a loss of function mutation in DNA Polymerase Delta 1. J Allergy Clin Immunol. 2019. 10.1016/j.jaci.2019.10.004.
    1. Badran YR, Dedeoglu F, Leyva Castillo JM, Bainter W, Ohsumi TK, Bousvaros A, et al. Human RELA haploinsufficiency results in autosomal-dominant chronic mucocutaneous ulceration. J Exp Med. 2017;214(7):1937–1947. doi: 10.1084/jem.20160724.
    1. Comrie WA, Faruqi AJ, Price S, Zhang Y, Rao VK, Su HC, et al. RELA haploinsufficiency in CD4 lymphoproliferative disease with autoimmune cytopenias. J Allergy Clin Immunol. 2018;141(4):1507–1510. doi: 10.1016/j.jaci.2017.11.036.
    1. Beaussant-Cohen S, Jaber F, Massaad MJ, Weeks S, Jones J, Alosaimi MF, et al. Combined immunodeficiency in a patient with c-Rel deficiency. J Allergy Clin Immunol. 2019;144(2):606–608. doi: 10.1016/j.jaci.2019.05.003.
    1. Calzoni E, Platt CD, Keles S, Kuehn HS, Beaussant-Cohen S, Zhang Y, et al. F-BAR domain only protein 1 (FCHO1) deficiency is a novel cause of combined immune deficiency in human subjects. J Allergy Clin Immunol. 2019;143(6):2317–2321. doi: 10.1016/j.jaci.2019.02.014.
    1. Maffucci P, Chavez J, Jurkiw TJ, O'Brien PJ, Abbott JK, Reynolds PR, et al. Biallelic mutations in DNA ligase 1 underlie a spectrum of immune deficiencies. J Clin Invest. 2018;128(12):5489–5504. doi: 10.1172/JCI99629.
    1. Bosticardo M, Yamazaki Y, Cowan J, Giardino G, Corsino C, Scalia G, et al. Heterozygous FOXN1 variants cause low TRECs and severe T cell Lymphopenia, revealing a crucial role of FOXN1 in supporting early Thymopoiesis. Am J Hum Genet. 2019;105(3):549–561. doi: 10.1016/j.ajhg.2019.07.014.
    1. Lyons JJ, Liu Y, Ma CA, Yu X, O'Connell MP, Lawrence MG, et al. ERBIN deficiency links STAT3 and TGF-beta pathway defects with atopy in humans. J Exp Med. 2017;214(3):669–680. doi: 10.1084/jem.20161435.
    1. Schepers D, Tortora G, Morisaki H, MacCarrick G, Lindsay M, Liang D, et al. A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3. Hum Mutat. 2018;39(5):621–634. doi: 10.1002/humu.23407.
    1. Fabre A, Charroux B, Martinez-Vinson C, Roquelaure B, Odul E, Sayar E, et al. SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric syndrome. Am J Hum Genet. 2012;90(4):689–692. doi: 10.1016/j.ajhg.2012.02.009.
    1. Huppke P, Weissbach S, Church JA, Schnur R, Krusen M, Dreha-Kulaczewski S, et al. Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder. Nat Commun. 2017;8(1):818. doi: 10.1038/s41467-017-00932-7.
    1. Rodriguez R, Fournier B, Cordeiro DJ, Winter S, Izawa K, Martin E, et al. Concomitant PIK3CD and TNFRSF9 deficiencies cause chronic active Epstein-Barr virus infection of T cells. J Exp Med. 2019. 10.1084/jem.20190678.
    1. Anzilotti C, Swan DJ, Boisson B, Deobagkar-Lele M, Oliveira C, Chabosseau P, et al. An essential role for the Zn(2+) transporter ZIP7 in B cell development. Nat Immunol. 2019;20(3):350–361. doi: 10.1038/s41590-018-0295-8.
    1. Broderick L, Yost S, Li D, McGeough MD, Booshehri LM, Guaderrama M, et al. Mutations in topoisomerase IIbeta result in a B cell immunodeficiency. Nat Commun. 2019;10(1):3644. doi: 10.1038/s41467-019-11570-6.
    1. Bouafia A, Lofek S, Bruneau J, Chentout L, Lamrini H, Trinquand A, et al. Loss of ARHGEF1 causes a human primary antibody deficiency. J Clin Invest. 2019;129(3):1047–1060. doi: 10.1172/JCI120572.
    1. Keller B, Shoukier M, Schulz K, Bhatt A, Heine I, Strohmeier V, et al. Germline deletion of CIN85 in humans with X chromosome-linked antibody deficiency. J Exp Med. 2018;215(5):1327–1336. doi: 10.1084/jem.20170534.
    1. Schubert D, Klein MC, Hassdenteufel S, Caballero-Oteyza A, Yang L, Proietti M, et al. Plasma cell deficiency in human subjects with heterozygous mutations in Sec61 translocon alpha 1 subunit (SEC61A1) J Allergy Clin Immunol. 2018;141(4):1427–1438. doi: 10.1016/j.jaci.2017.06.042.
    1. Mauhin W, Habarou F, Gobin S, Servais A, Brassier A, Grisel C, et al. Update on Lysinuric protein intolerance, a multi-faceted disease retrospective cohort analysis from birth to adulthood. Orphanet J Rare Dis. 2017;12(1):3. doi: 10.1186/s13023-016-0550-8.
    1. Fernandez IZ, Baxter RM, Garcia-Perez JE, Vendrame E, Ranganath T, Kong DS, et al. A novel human IL2RB mutation results in T and NK cell-driven immune dysregulation. J Exp Med. 2019;216(6):1255–1267. doi: 10.1084/jem.20182015.
    1. Zhang Z, Gothe F, Pennamen P, James JR, McDonald D, Mata CP, et al. Human interleukin-2 receptor beta mutations associated with defects in immunity and peripheral tolerance. J Exp Med. 2019;216(6):1311–1327. doi: 10.1084/jem.20182304.
    1. Has C, Castiglia D, del Rio M, Diez MG, Piccinni E, Kiritsi D, et al. Kindler syndrome: extension of FERMT1 mutational spectrum and natural history. Hum Mutat. 2011;32(11):1204–1212. doi: 10.1002/humu.21576.
    1. Kotlarz D, Marquardt B, Baroy T, Lee WS, Konnikova L, Hollizeck S, et al. Human TGF-beta1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nat Genet. 2018;50(3):344–348. doi: 10.1038/s41588-018-0063-6.
    1. Cuchet-Lourenco D, Eletto D, Wu C, Plagnol V, Papapietro O, Curtis J, et al. Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation. Science. 2018;361(6404):810–813. doi: 10.1126/science.aar2641.
    1. Li Y, Fuhrer M, Bahrami E, Socha P, Klaudel-Dreszler M, Bouzidi A, et al. Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2019;116(3):970–975. doi: 10.1073/pnas.1813582116.
    1. Alosaimi MF, Hoenig M, Jaber F, Platt CD, Jones J, Wallace J, et al. Immunodeficiency and EBV-induced lymphoproliferation caused by 4-1BB deficiency. J Allergy Clin Immunol. 2019;144(2):574–83 e5. doi: 10.1016/j.jaci.2019.03.002.
    1. Somekh I, Thian M, Medgyesi D, Gulez N, Magg T, Gallon Duque A, et al. CD137 deficiency causes immune dysregulation with predisposition to lymphomagenesis. Blood. 2019. 10.1182/blood.2019000644.
    1. Carapito R, Konantz M, Paillard C, Miao Z, Pichot A, Leduc MS, et al. Mutations in signal recognition particle SRP54 cause syndromic neutropenia with Shwachman-diamond-like features. J Clin Invest. 2017;127(11):4090–4103. doi: 10.1172/JCI92876.
    1. Bellanne-Chantelot C, Schmaltz-Panneau B, Marty C, Fenneteau O, Callebaut I, Clauin S, et al. Mutations in the SRP54 gene cause severe congenital neutropenia as well as Shwachman-diamond-like syndrome. Blood. 2018;132(12):1318–1331. doi: 10.1182/blood-2017-12-820308.
    1. Dhanraj S, Matveev A, Li H, Lauhasurayotin S, Jardine L, Cada M, et al. Biallelic mutations in DNAJC21 cause Shwachman-diamond syndrome. Blood. 2017;129(11):1557–1562. doi: 10.1182/blood-2016-08-735431.
    1. Arnadottir GA, Norddahl GL, Gudmundsdottir S, Agustsdottir AB, Sigurdsson S, Jensson BO, et al. A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease. Nat Commun. 2018;9(1):4447. doi: 10.1038/s41467-018-06964-x.
    1. Thomas DC, Charbonnier LM, Schejtman A, Aldhekri H, Coomber EL, Dufficy ER, et al. EROS/CYBC1 mutations: decreased NADPH oxidase function and chronic granulomatous disease. J Allergy Clin Immunol. 2019;143(2):782–785. doi: 10.1016/j.jaci.2018.09.019.
    1. de Jong SJ, Crequer A, Matos I, Hum D, Gunasekharan V, Lorenzo L, et al. The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to beta-papillomaviruses. J Exp Med. 2018;215(9):2289–2310. doi: 10.1084/jem.20170308.
    1. Hernandez N, Bucciol G, Moens L, Le Pen J, Shahrooei M, Goudouris E, et al. Inherited IFNAR1 deficiency in otherwise healthy patients with adverse reaction to measles and yellow fever live vaccines. J Exp Med. 2019;216(9):2057–2070. doi: 10.1084/jem.20182295.
    1. Ogunjimi B, Zhang SY, Sorensen KB, Skipper KA, Carter-Timofte M, Kerner G, et al. Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections. J Clin Invest. 2017;127(9):3543–3556. doi: 10.1172/JCI92280.
    1. Carter-Timofte ME, Hansen AF, Mardahl M, Fribourg S, Rapaport F, Zhang SY, et al. Varicella-zoster virus CNS vasculitis and RNA polymerase III gene mutation in identical twins. Neurol Neuroimmunol Neuroinflamm. 2018;5(6):e500. doi: 10.1212/NXI.0000000000000500.
    1. Zhang SY, Clark NE, Freije CA, Pauwels E, Taggart AJ, Okada S, et al. Inborn errors of RNA lariat metabolism in humans with brainstem viral infection. Cell. 2018;172(5):952–965. doi: 10.1016/j.cell.2018.02.019.
    1. Guerin A, Kerner G, Marr N, Markle JG, Fenollar F, Wong N, et al. IRF4 haploinsufficiency in a family with Whipple's disease. Elife. 2018;7. 10.7554/eLife.32340.
    1. Brehm A, Liu Y, Sheikh A, Marrero B, Omoyinmi E, Zhou Q, et al. Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Invest. 2015;125(11):4196–4211. doi: 10.1172/JCI81260.
    1. Rodero MP, Tesser A, Bartok E, Rice GI, Della Mina E, Depp M, et al. Type I interferon-mediated autoinflammation due to DNase II deficiency. Nat Commun. 2017;8(1):2176. doi: 10.1038/s41467-017-01932-3.
    1. Al-Mayouf SM, Sunker A, Abdwani R, Abrawi SA, Almurshedi F, Alhashmi N, et al. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat Genet. 2011;43(12):1186–1188. doi: 10.1038/ng.975.
    1. Ozcakar ZB, Foster J, 2nd, Diaz-Horta O, Kasapcopur O, Fan YS, Yalcinkaya F, et al. DNASE1L3 mutations in hypocomplementemic urticarial vasculitis syndrome. Arthritis Rheum. 2013;65(8):2183–2189. doi: 10.1002/art.38010.
    1. Carbonella A, Mancano G, Gremese E, Alkuraya FS, Patel N, Gurrieri F, et al. An autosomal recessive DNASE1L3-related autoimmune disease with unusual clinical presentation mimicking systemic lupus erythematosus. Lupus. 2017;26(7):768–772. doi: 10.1177/0961203316676382.
    1. Cho K, Yamada M, Agematsu K, Kanegane H, Miyake N, Ueki M, et al. Heterozygous mutations in OAS1 cause infantile-onset pulmonary alveolar Proteinosis with Hypogammaglobulinemia. Am J Hum Genet. 2018;102(3):480–486. doi: 10.1016/j.ajhg.2018.01.019.
    1. Zhong FL, Mamai O, Sborgi L, Boussofara L, Hopkins R, Robinson K, et al. Germline NLRP1 mutations cause skin inflammatory and Cancer susceptibility syndromes via Inflammasome activation. Cell. 2016;167(1):187–202. doi: 10.1016/j.cell.2016.09.001.
    1. Drutman SB, Haerynck F, Zhong FL, Hum D, Hernandez NJ, Belkaya S, et al. Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic form of recurrent respiratory papillomatosis. Proc Natl Acad Sci U S A. 2019;116(38):19055–19063. doi: 10.1073/pnas.1906184116.
    1. Parlato M, Charbit-Henrion F, Pan J, Romano C, Duclaux-Loras R, Le Du MH, et al. Human ALPI deficiency causes inflammatory bowel disease and highlights a key mechanism of gut homeostasis. EMBO Mol Med. 2018;10(4). 10.15252/emmm.201708483.
    1. Li Q, Lee CH, Peters LA, Mastropaolo LA, Thoeni C, Elkadri A, et al. Variants in TRIM22 that affect NOD2 signaling are associated with very-early-onset inflammatory bowel disease. Gastroenterology. 2016;150(5):1196–1207. doi: 10.1053/j.gastro.2016.01.031.
    1. de Jesus AA, Brehm A, VanTries R, Pillet P, Parentelli AS, Montealegre Sanchez GA, et al. Novel proteasome assembly chaperone mutations in PSMG2/PAC2 cause the autoinflammatory interferonopathy CANDLE/PRAAS4. J Allergy Clin Immunol. 2019;143(5):1939–1943. doi: 10.1016/j.jaci.2018.12.1012.
    1. Gayden T, Sepulveda FE, Khuong-Quang DA, Pratt J, Valera ET, Garrigue A, et al. Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome. Nat Genet. 2018;50(12):1650–1657. doi: 10.1038/s41588-018-0251-4.
    1. Polprasert C, Takeuchi Y, Kakiuchi N, Yoshida K, Assanasen T, Sitthi W, et al. Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma. Blood Adv. 2019;3(4):588–595. doi: 10.1182/bloodadvances.2018028340.
    1. Kapferer-Seebacher I, Pepin M, Werner R, Aitman TJ, Nordgren A, Stoiber H, et al. Periodontal Ehlers-Danlos syndrome is caused by mutations in C1R and C1S, which encode subcomponents C1r and C1s of complement. Am J Hum Genet. 2016;99(5):1005–1014. doi: 10.1016/j.ajhg.2016.08.019.

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