Defects in intrinsic and innate immunity
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Immunodeficiency Main Page |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Zahir Ali Shaikh, MD[2], Anmol Pitliya, M.B.B.S. M.D.[3]
Overview
Classification
| Defects in Intrinsic & Innate Immunity | |||||||||||||||
| (A) Bacterial and Parasitic Infections | (B) MSMD & Viral Infections | ||||||||||||||
Bacterial and Parasitic infections
| Defects in Intrinsic & Innate Immunity: (A) Bacterial and Parasitic Infections | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Predisposition to Invasive Bacterial Infections (pyrogens) | Predisposition to Parasitic & Fungal Infections | Others | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IRAK4 Deficiency, IRAK4, AR, MyD88 Deficiency, MYD88, AR | Osteopetrosis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IRAK-1 Deficiency:IRAK1,XL | Predisposition to mucocutaneous candidiasis(CMC) | CARD9 Deficiency, CARD9, AR | Hyderadenitis Suppurativa | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| TIRAP Deficiency, TIRAP, AR | STAT1 GOF, STAT1, AD | Trypanosomiasis APOL1, AD | Acute liver failure due to NBAS deficiency, NBAS, AR | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Isolated Congenital Asplenia, RPSA, AD; HMOX, AR | IL-17F Deficiency, IL-17F, AD | Acute necrotizing encephalopathy, RANBP2, AD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IL-17RA Deficiency, IL-17RA, AR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IL-17RC Deficiency, IL-17RC, AR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ACT1 Deficiency, ACT1, AR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
MSMD and Viral Infections
| Defects in Intrinsic & Innate Immunity: (B) MSMD & Viral Infections | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendelian susceptibility to mycobacterial disease(MSMD) | Predominant susceptibility to viral infections | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Severe Phenotypes | Moderate Phenotypes | Epidermodysplasia verruciformis(HPV) | Predisposition to severe viral infections | Herpes simplex encephalitis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Complete IFNGR1 def: and IFNGR2 def:, IFNGR1,IFNGR2,AR | IL12 & 23 receptor B1 chain def:, IL12P40 def:, STAT1 LOF, Partial IFNYR1 & 2, AD IFNGR1, TyK2 def: | EVER1 def:, TMC6, AR | STAT1 def: (AR LOF) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ISG15 def:, ISG15,AR; Macrophage Gp91 Phox def:CYBB,XL,IRG8 def:,IRF8,AD; IRF8 def:, IRF8 AR; RORc def:, ROCR,AR; JACK1(LOF),JAK1,AR | EVER2 def:, TMC8,AR | STAT2 def: (STAT2 AR) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) Syndrome, CXCR4, AD,GOF | IRF7 def: (IRF7,AR) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IFNAR2 def: (IFNAR2,AR) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CD16 def: (FCGR3A,AR) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| MDAS def: (LOF), IFIH1,AR | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
IRAK4 Deficiency
- IRAK4 (interleukin 1 receptor associated kinase 4) gene located on chromosome 12q12 encodes a kinase that activates NF-kappaB in both the toll-like receptor (TLR) and T-cell receptor (TCR) signalling pathways. The protein is essential for most innate immune responses.[1]
- IRAK4 deficiency presents with recurrent noninvasive and invasive bacterial infections especially with pseudomonas aeruginosa, staphylococcus aureus and pneumococcus, and poor inflammatory response.[2][3]
- Treatment includes; management of complications, antibiotic prophylaxis and pneumococcal vaccine.[3]
IRAK1 Deficiency
- IRAK1 (interleukin 1 receptor associated kinase 1) gene located on chromosome Xq28 encodes one of two putative serine/threonine kinases that become associated with interleukin 1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL-1 induced upregulation of transcription factor NF-kappaB.[4]
- IRAK1 deficiency can present with SLE like syndrome, autoimmunity, IgM & IgG autoantibodies, lymphocytic activation and renal disease.[5]
TIRAP Deficiency
- TIRAP (TIR domain containing adaptor protein) gene located on chromosome 11q24.2 encodes a toll interleukin 1 receptor (TIR) protein involved in TLR4 signalling pathway of immune system. It activates NF-kappaB, MAPK1, MAPK3 and JNK, which then results in cytokine secretion and the inflammatory response.[6]
- TIRAP deficiency can present with disordered innate immune responses and life threatening staphylococcal disease.[7]
- Treatment includes; prophylactic antibiotics, vaccinations and immunoglobulin replacement therapy.[8]
RPSA Deficiency
- RPSA (ribosomal protein SA) gene located on chromosome 3p22.1 encodes a high-affinity, non-integrin family, laminin receptor 1. This receptor has been variously called 67 kD laminin receptor, 37 kD laminin receptor precursor (37LRP) and p40 ribosome-associated protein. The level of the laminin receptor transcript is higher in colon carcinoma tissue and lung cancer cell line than their normal counterparts.[9]
- RPSA haploinsufficiency causes isolated congenital asplenia (ICA) with life threatening bacterial infections.[10]
- Treatment includes; pneumococcal vaccine, antibiotic prophylaxis, preemptive investigation and emperic treatment early in the course of disease.[11]
STAT1 GOF
- STAT1 (signal transducer & activator of transcription 1) gene located on chromosome 2q32.2 encodes a protein member of the STAT protein family. When activated, STAT family members translocate to the cell nucleus where they act as transcription activators. It is activated by various ligands including interferon-alpha, interferon-gamma, EGF, PDGF and IL6 and is thought to be important for cell viability in response to different cell stimuli and pathogens.[12]
- STAT1 GOF (gain of function) mutation can present with chronic mucocutaneous candidiasis (CMC), autoimmune thyroid & skin disease,cerebral aneurysms, squamous cell carcinoma and bone fragility.[13]
- Treatment includes; antibiotic prophylaxis, IgG infusion, ruxolitinib and hematopoietic stem cell transplantation (HST).[14]
IL17F Deficiency
- IL17F (interleukin 17F) gene located on chromosome 6p12.2 encodes a protein cytokine that shares sequence similarity with IL17. It is expressed by activated T cells and stimulates the production of several other cytokines including IL6, IL8 and CSF2/GM_CSF. It also inhibits angiogensis of endothelial cells.[15]
- IL17F deficiency can cause; recurrent mucocutaneous candidiasis, recurrent aphthous stomatitis (RAS) and enterovirus 71 (EV71) infection causing hand foot & mouth disease (HFMD).[16][17]
- Treatment includes; management of the complications and immunosuppresive drugs.[18]
IL17RA Deficiency
IL17RC Deficiency
ACT1 Deficiency
CARD9 Deficiency
Trypanosomiasis APOL1
Osteopetrosis
Hideradenitis Suppurativa
NBAS Deficiency
RANBP2 Deficiency
P
Q
R
S
T
U
V
W
X
Y
Z
References
- ↑ Linn Fagerberg, Bjorn M. Hallstrom, Per Oksvold, Caroline Kampf, Dijana Djureinovic, Jacob Odeberg, Masato Habuka, Simin Tahmasebpoor, Angelika Danielsson, Karolina Edlund, Anna Asplund, Evelina Sjostedt, Emma Lundberg, Cristina Al-Khalili Szigyarto, Marie Skogs, Jenny Ottosson Takanen, Holger Berling, Hanna Tegel, Jan Mulder, Peter Nilsson, Jochen M. Schwenk, Cecilia Lindskog, Frida Danielsson, Adil Mardinoglu, Asa Sivertsson, Kalle von Feilitzen, Mattias Forsberg, Martin Zwahlen, IngMarie Olsson, Sanjay Navani, Mikael Huss, Jens Nielsen, Fredrik Ponten & Mathias Uhlen (2014). "Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics". Molecular & cellular proteomics : MCP. 13 (2): 397–406. doi:10.1074/mcp.M113.035600. PMID 24309898. Unknown parameter
|month=ignored (help) - ↑ Capucine Picard, Anne Puel, Marion Bonnet, Cheng-Lung Ku, Jacinta Bustamante, Kun Yang, Claire Soudais, Stephanie Dupuis, Jacqueline Feinberg, Claire Fieschi, Carole Elbim, Remi Hitchcock, David Lammas, Graham Davies, Abdulaziz Al-Ghonaium, Hassan Al-Rayes, Sulaiman Al-Jumaah, Sami Al-Hajjar, Ibrahim Zaid Al-Mohsen, Husn H. Frayha, Rajivi Rucker, Thomas R. Hawn, Alan Aderem, Haysam Tufenkeji, Soichi Haraguchi, Noorbibi K. Day, Robert A. Good, Marie-Anne Gougerot-Pocidalo, Adrian Ozinsky & Jean-Laurent Casanova (2003). "Pyogenic bacterial infections in humans with IRAK-4 deficiency". Science (New York, N.Y.). 299 (5615): 2076–2079. doi:10.1126/science.1081902. PMID 12637671. Unknown parameter
|month=ignored (help) - ↑ 3.0 3.1 Takada, Hidetoshi; Ishimura, Masataka; Takimoto, Tomohito; Kohagura, Toaki; Yoshikawa, Hideto; Imaizumi, Masue; Shichijyou, Koichi; Shimabukuro, Yoko; Kise, Tomoo; Hyakuna, Nobuyuki; Ohara, Osamu; Nonoyama, Shigeaki; Hara, Toshiro (2016). "Invasive Bacterial Infection in Patients with Interleukin-1 Receptor-associated Kinase 4 Deficiency". Medicine. 95 (4): e2437. doi:10.1097/MD.0000000000002437. ISSN 0025-7974.
- ↑ Linn Fagerberg, Bjorn M. Hallstrom, Per Oksvold, Caroline Kampf, Dijana Djureinovic, Jacob Odeberg, Masato Habuka, Simin Tahmasebpoor, Angelika Danielsson, Karolina Edlund, Anna Asplund, Evelina Sjostedt, Emma Lundberg, Cristina Al-Khalili Szigyarto, Marie Skogs, Jenny Ottosson Takanen, Holger Berling, Hanna Tegel, Jan Mulder, Peter Nilsson, Jochen M. Schwenk, Cecilia Lindskog, Frida Danielsson, Adil Mardinoglu, Asa Sivertsson, Kalle von Feilitzen, Mattias Forsberg, Martin Zwahlen, IngMarie Olsson, Sanjay Navani, Mikael Huss, Jens Nielsen, Fredrik Ponten & Mathias Uhlen (2014). "Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics". Molecular & cellular proteomics : MCP. 13 (2): 397–406. doi:10.1074/mcp.M113.035600. PMID 24309898. Unknown parameter
|month=ignored (help) - ↑ Chaim O. Jacob, Jiankun Zhu, Don L. Armstrong, Mei Yan, Jie Han, Xin J. Zhou, James A. Thomas, Andreas Reiff, Barry L. Myones, Joshua O. Ojwang, Kenneth M. Kaufman, Marisa Klein-Gitelman, Deborah McCurdy, Linda Wagner-Weiner, Earl Silverman, Julie Ziegler, Jennifer A. Kelly, Joan T. Merrill, John B. Harley, Rosalind Ramsey-Goldman, Luis M. Vila, Sang-Cheol Bae, Timothy J. Vyse, Gary S. Gilkeson, Patrick M. Gaffney, Kathy L. Moser, Carl D. Langefeld, Raphael Zidovetzki & Chandra Mohan (2009). "Identification of IRAK1 as a risk gene with critical role in the pathogenesis of systemic lupus erythematosus". Proceedings of the National Academy of Sciences of the United States of America. 106 (15): 6256–6261. doi:10.1073/pnas.0901181106. PMID 19329491. Unknown parameter
|month=ignored (help) - ↑ Linn Fagerberg, Bjorn M. Hallstrom, Per Oksvold, Caroline Kampf, Dijana Djureinovic, Jacob Odeberg, Masato Habuka, Simin Tahmasebpoor, Angelika Danielsson, Karolina Edlund, Anna Asplund, Evelina Sjostedt, Emma Lundberg, Cristina Al-Khalili Szigyarto, Marie Skogs, Jenny Ottosson Takanen, Holger Berling, Hanna Tegel, Jan Mulder, Peter Nilsson, Jochen M. Schwenk, Cecilia Lindskog, Frida Danielsson, Adil Mardinoglu, Asa Sivertsson, Kalle von Feilitzen, Mattias Forsberg, Martin Zwahlen, IngMarie Olsson, Sanjay Navani, Mikael Huss, Jens Nielsen, Fredrik Ponten & Mathias Uhlen (2014). "Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics". Molecular & cellular proteomics : MCP. 13 (2): 397–406. doi:10.1074/mcp.M113.035600. PMID 24309898. Unknown parameter
|month=ignored (help) - ↑ Laura Israel, Ying Wang, Katarzyna Bulek, Erika Della Mina, Zhao Zhang, Vincent Pedergnana, Maya Chrabieh, Nicole A. Lemmens, Vanessa Sancho-Shimizu, Marc Descatoire, Theo Lasseau, Elisabeth Israelsson, Lazaro Lorenzo, Ling Yun, Aziz Belkadi, Andrew Moran, Leonard E. Weisman, Francois Vandenesch, Frederic Batteux, Sandra Weller, Michael Levin, Jethro Herberg, Avinash Abhyankar, Carolina Prando, Yuval Itan, Willem J. B. van Wamel, Capucine Picard, Laurent Abel, Damien Chaussabel, Xiaoxia Li, Bruce Beutler, Peter D. Arkwright, Jean-Laurent Casanova & Anne Puel (2017). "Human Adaptive Immunity Rescues an Inborn Error of Innate Immunity". Cell. 168 (5): 789–800. doi:10.1016/j.cell.2017.01.039. PMID 28235196. Unknown parameter
|month=ignored (help) - ↑ Paul J. Maglione, Noa Simchoni & Charlotte Cunningham-Rundles (2015). "Toll-like receptor signaling in primary immune deficiencies". Annals of the New York Academy of Sciences. 1356: 1–21. doi:10.1111/nyas.12763. PMID 25930993. Unknown parameter
|month=ignored (help) - ↑ Linn Fagerberg, Bjorn M. Hallstrom, Per Oksvold, Caroline Kampf, Dijana Djureinovic, Jacob Odeberg, Masato Habuka, Simin Tahmasebpoor, Angelika Danielsson, Karolina Edlund, Anna Asplund, Evelina Sjostedt, Emma Lundberg, Cristina Al-Khalili Szigyarto, Marie Skogs, Jenny Ottosson Takanen, Holger Berling, Hanna Tegel, Jan Mulder, Peter Nilsson, Jochen M. Schwenk, Cecilia Lindskog, Frida Danielsson, Adil Mardinoglu, Asa Sivertsson, Kalle von Feilitzen, Mattias Forsberg, Martin Zwahlen, IngMarie Olsson, Sanjay Navani, Mikael Huss, Jens Nielsen, Fredrik Ponten & Mathias Uhlen (2014). "Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics". Molecular & cellular proteomics : MCP. 13 (2): 397–406. doi:10.1074/mcp.M113.035600. PMID 24309898. Unknown parameter
|month=ignored (help) - ↑ Alexandre Bolze, Nizar Mahlaoui, Minji Byun, Bridget Turner, Nikolaus Trede, Steven R. Ellis, Avinash Abhyankar, Yuval Itan, Etienne Patin, Samuel Brebner, Paul Sackstein, Anne Puel, Capucine Picard, Laurent Abel, Lluis Quintana-Murci, Saul N. Faust, Anthony P. Williams, Richard Baretto, Michael Duddridge, Usha Kini, Andrew J. Pollard, Catherine Gaud, Pierre Frange, Daniel Orbach, Jean-Francois Emile, Jean-Louis Stephan, Ricardo Sorensen, Alessandro Plebani, Lennart Hammarstrom, Mary Ellen Conley, Licia Selleri & Jean-Laurent Casanova (2013). "Ribosomal protein SA haploinsufficiency in humans with isolated congenital asplenia". Science (New York, N.Y.). 340 (6135): 976–978. doi:10.1126/science.1234864. PMID 23579497. Unknown parameter
|month=ignored (help) - ↑ Shigeo Iijima (2017). "Sporadic isolated congenital asplenia with fulminant pneumococcal meningitis: a case report and updated literature review". BMC infectious diseases. 17 (1): 777. doi:10.1186/s12879-017-2896-5. PMID 29254492. Unknown parameter
|month=ignored (help) - ↑ Linn Fagerberg, Bjorn M. Hallstrom, Per Oksvold, Caroline Kampf, Dijana Djureinovic, Jacob Odeberg, Masato Habuka, Simin Tahmasebpoor, Angelika Danielsson, Karolina Edlund, Anna Asplund, Evelina Sjostedt, Emma Lundberg, Cristina Al-Khalili Szigyarto, Marie Skogs, Jenny Ottosson Takanen, Holger Berling, Hanna Tegel, Jan Mulder, Peter Nilsson, Jochen M. Schwenk, Cecilia Lindskog, Frida Danielsson, Adil Mardinoglu, Asa Sivertsson, Kalle von Feilitzen, Mattias Forsberg, Martin Zwahlen, IngMarie Olsson, Sanjay Navani, Mikael Huss, Jens Nielsen, Fredrik Ponten & Mathias Uhlen (2014). "Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics". Molecular & cellular proteomics : MCP. 13 (2): 397–406. doi:10.1074/mcp.M113.035600. PMID 24309898. Unknown parameter
|month=ignored (help) - ↑ Julie Toubiana, Satoshi Okada, Julia Hiller, Matias Oleastro, Macarena Lagos Gomez, Juan Carlos Aldave Becerra, Marie Ouachee-Chardin, Fanny Fouyssac, Katta Mohan Girisha, Amos Etzioni, Joris Van Montfrans, Yildiz Camcioglu, Leigh Ann Kerns, Bernd Belohradsky, Stephane Blanche, Aziz Bousfiha, Carlos Rodriguez-Gallego, Isabelle Meyts, Kai Kisand, Janine Reichenbach, Ellen D. Renner, Sergio Rosenzweig, Bodo Grimbacher, Frank L. van de Veerdonk, Claudia Traidl-Hoffmann, Capucine Picard, Laszlo Marodi, Tomohiro Morio, Masao Kobayashi, Desa Lilic, Joshua D. Milner, Steven Holland, Jean-Laurent Casanova & Anne Puel (2016). "Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype". Blood. 127 (25): 3154–3164. doi:10.1182/blood-2015-11-679902. PMID 27114460. Unknown parameter
|month=ignored (help) - ↑ Julie Toubiana, Satoshi Okada, Julia Hiller, Matias Oleastro, Macarena Lagos Gomez, Juan Carlos Aldave Becerra, Marie Ouachee-Chardin, Fanny Fouyssac, Katta Mohan Girisha, Amos Etzioni, Joris Van Montfrans, Yildiz Camcioglu, Leigh Ann Kerns, Bernd Belohradsky, Stephane Blanche, Aziz Bousfiha, Carlos Rodriguez-Gallego, Isabelle Meyts, Kai Kisand, Janine Reichenbach, Ellen D. Renner, Sergio Rosenzweig, Bodo Grimbacher, Frank L. van de Veerdonk, Claudia Traidl-Hoffmann, Capucine Picard, Laszlo Marodi, Tomohiro Morio, Masao Kobayashi, Desa Lilic, Joshua D. Milner, Steven Holland, Jean-Laurent Casanova & Anne Puel (2016). "Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype". Blood. 127 (25): 3154–3164. doi:10.1182/blood-2015-11-679902. PMID 27114460. Unknown parameter
|month=ignored (help) - ↑ Linn Fagerberg, Bjorn M. Hallstrom, Per Oksvold, Caroline Kampf, Dijana Djureinovic, Jacob Odeberg, Masato Habuka, Simin Tahmasebpoor, Angelika Danielsson, Karolina Edlund, Anna Asplund, Evelina Sjostedt, Emma Lundberg, Cristina Al-Khalili Szigyarto, Marie Skogs, Jenny Ottosson Takanen, Holger Berling, Hanna Tegel, Jan Mulder, Peter Nilsson, Jochen M. Schwenk, Cecilia Lindskog, Frida Danielsson, Adil Mardinoglu, Asa Sivertsson, Kalle von Feilitzen, Mattias Forsberg, Martin Zwahlen, IngMarie Olsson, Sanjay Navani, Mikael Huss, Jens Nielsen, Fredrik Ponten & Mathias Uhlen (2014). "Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics". Molecular & cellular proteomics : MCP. 13 (2): 397–406. doi:10.1074/mcp.M113.035600. PMID 24309898. Unknown parameter
|month=ignored (help) - ↑ Fei Li, Peipei Liu, Ya Guo, Zhenliang Han, Yedan Liu, Yuanyuan Wang, Long Song, Jianguo Cheng & Zongbo Chen (2018). "Association of Interleukin-17F gene polymorphisms with susceptibility to severe enterovirus 71 infection in Chinese children". Archives of virology. 163 (7): 1933–1939. doi:10.1007/s00705-018-3807-9. PMID 29549443. Unknown parameter
|month=ignored (help) - ↑ Alireza Zare Bidoki, Ahmad Massoud, Shamsolmoulouk Najafi, Mahsa Mohammadzadeh & Nima Rezaei (2018). "Autosomal dominant deficiency of the interleukin-17F in recurrent aphthous stomatitis: Possible novel mutation in a new entity". Gene. 654: 64–68. doi:10.1016/j.gene.2018.02.041. PMID 29458167. Unknown parameter
|month=ignored (help) - ↑ Anna R. Huppler, Shrinivas Bishu & Sarah L. Gaffen (2012). "Mucocutaneous candidiasis: the IL-17 pathway and implications for targeted immunotherapy". Arthritis research & therapy. 14 (4): 217. doi:10.1186/ar3893. PMID 22838497. Unknown parameter
|month=ignored (help)