Abstract
Essential human immunome is composed of about 900 genes and proteins. Primary immunodeficiencies (IDs) are a large and heterogenic group of inherited disorders of the immune system. Since defects in any part of the adaptive or innate immune system can cause disorders, numerous IDs have been detected. Immunodeficiency patients have increased susceptibility to recurrent and persistent, even life-threatening infections. Other symptoms vary greatly between IDs. To date, some 200 IDs and 150 affected genes have been identified. ID-related genes are distributed throughout the genome. Features of IDs and information sources for them are discussed. Genotype–phenotype correlations are rather rare for IDs. Those diseases in which mutation type has effect on disease phenotype are described. ImmunoDeficiency Resource (IDR) is a comprehensive knowledge base for all essential information about IDs. The service is freely available at http://bioinf.uta.fi/IDR. IDdiagnostics (http://bioinf.uta.fi/IDdiagnostics) is dedicated to health professionals looking for laboratories performing gene and clinical tests for IDs. ID mutation data can be accessed in locus-specific, patient-related mutation databases, IDbases (http://bioinf.uta.fi/IDbases). Mutations are described at DNA, mRNA, and protein levels, with links to reference sequences and reference articles. The mutation data have been collated into entries, along with some clinical information. Currently, we have databases for 123 ID genes with 5359 patient entries. Immunome genes and proteins, their evolution, mouse–human comparisons, phylogenetics trees and orthologs for Metazoan immunome entities are available in Immunome Database, ImmTree, and ImmunomeBase all of which can be accessed via Immunome Knowledge Base (IKB) (http://bioinf.uta.fi/IKB).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., Harris, M. A., Hill, D. P., Issel-Tarver L., Kasarskis, A., Lewis, S., Matese, J. C., Richardson, J. E., Ringwald, M., Rubin, G. M., Sherlock, G. 2000. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25:25–29.
Altschul, S. F., Madden, T. L., Schäffer, A. A., Zhang, J., Zhang, Z., Miller, W., Lipman, D. J. 1997. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25:3389–3402.
Antonarakis, S. E., Ashburner, M., Auerbach, A. D., Beaudet, A. L., Beckmann, J. S., Beutler, E., Cooper, D. N., Cotton, R. G. H., den Dunnen, J. T., Desnick, R. J., Eng, C., Fasman, K. H., Goldman, D., Hayashi, K., Hutchinson, F., Kazazian, H. H., Keen, J., King, M.-C., Lehväslaiho, H., McAlpine, P. J., McKusick, V., Motulski, A. G., Povey, S., Schorderet, D., Scriver, C. R., Shows, T. B., Superti-Furga, A., Tay, A. H. N., Tsui, L.-C., Valle, D., Vihinen, M. 1998. Recommendations for a nomenclature system for human gene mutations. Hum. Mut. 11: 1–3
Arredondo-Vega, F. X., Santisteban, I., Daniels, S., Toutain, S., Hershfield, M. S. 1998. Adenosine deaminase deficiency: genotype-phenotype correlations based on expressed activity of 29 mutant alleles. Am. J. Hum. Genet. 63:1049–1059.
Bonilla, F. A., Bernstein, I. L., Khan, D. A., Ballas, Z. K., Chinen, J., Frank, M. M., Kobrynski, L. J., Levinson, A. I., Mazer, B., Nelson, R. P. Jr., Orange, J. S., Routes, J. M., Shearer, W. T., Sorensen, R.U. 2005. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann. Allergy Asthma Immunol. 94: S1–S63.
Bruford, E. A., Lush, M. J., Wright, M.W., Sneddon, T. P., Povey, S., Birney, E. 2008. The HGNC Database in 2008: a resource for the human genome. Nucleic Acids Res. 36:D445–448.
Cavazzana-Calvo, M., Hacein-Bey, S., de Saint Basile, G., Gross, F., Yvon, E., Nusbaum, P., Selz, F., Hue, C., Certain, S., Casanova, J. L., Bousso, P., Deist, F. L., Fischer A. 2000. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 288, 669–672.
Castigli E, Wilson, S. A., Garibyan, L., Rachid, R., Bonilla, F., Schneider, L., Geha, R. S. 2005. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat. Genet. 37:829–834.
Conley, M. E., Notarangelo, L. D., Etzioni, A. 1999. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin. Immunol. 93:190–197.
Cotton, R. G. H., Auerbach, A. D., Beckmann J. S., Blumenfeld, O. O., Brookes, A. J., Brown, A. F., Carrera, P., Cox, D. W., Gottlieb, B., Greenblatt, M. S., Hilbert, P., Lehvaslaiho, H., Liang, P., Marsh, S., Nebert, D. W., Povey, A., Rossetti, S., Scriver, C. R., Summar, M., Tolan, D. R., Verma, I. C., Vihinen, M., den Dunnen, J. T. 2008. Recommendations for locus specific databases and their curation. Hum. Mut. 29:2–5.
Dale, D. C., Person, R. E., Bolyard, A. A., Aprikyan, A. G., Bos, C., Bonilla, M. A., Boxer, L. A., Kannourakis, G., Zeidler, C., Welte, K., Benson, K. F., Horwitz, M. 2000. Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood 96:2317–2322.
den Dunnen, J. T., Antonarakis, S. E. 2000. Mutation nomenclature extensions and suggestions to describe complex mutations: A discussion. Hum. Mut. 15:7–12.
Eades-Perner, A. M., Gathmann, B., Knerr, V., Guzman, D., Veit, D., Kindle, G., Grimbacher, B. 2007. The European internet-based patient and research database for primary immunodeficiencies: results 2004–06. Clin Exp Immunol. 147:306–312.
Fischer, A., Hacein-Bey, S., Cavazzana-Calvo, M. 2002. Gene therapy of severe combined immunodeficiencies. Nat. Rev. Immunol. 8:615–621.
Giardine, B., Riemer, C., Hefferon, T., Thomas, D., Hsu, F., Zielenski, J., Sang, Y., Elnitski, L., Cutting, G., Trumbower, H., Kern, A., Kuhn, R., Patrinos, G. P., Hughes, J., Higgs, D., Chui, D., Scriver, C., Phommarinh, M., Patnaik, S. K., Blumenfeld, O., Gottlieb, B., Vihinen, M., Väliaho, J., Kent, J., Miller, W., Hardison, R. C. 2007. PhenCode: connecting ENCODE data with mutations and phenotype. Hum. Mut. 28:554–562.
Hershfield, M.S. 2003. Genotype is an important determinant of phenotype in adenosine deaminase deficiency. Curr. Opin. Immunol. 15:571–577.
Imai, K., Nonoyama, S., Ochs, H.D. 2003. WASP (Wiskott-Aldrich syndrome protein) gene mutations and phenotype. Curr. Opin. Allergy Clin. Immunol. 3:427–436.
Infante, A. J., Britton, H. A., DeNapoli, T., Middelton, L. A., Lenardo, M. J., Jackson, C. E., Wang, J., Fleisher, T., Straus, S. E., Puck, J. M. 1998. The clinical spectrum in a large kindred with autoimmune lymphoproliferative syndrome caused by a Fas mutation that impairs lymphocyte apoptosis. J. Pediatr. 133:629–633.
Johnston, J., Kelley, R. I., Feigenbaum, A., Cox, G. F., Iyer, G. S., Funanage, V. L., Proujansky, R. 1997. Am. J. Hum. Genet. 61:1053–1058.
Lindvall, J. M., Blomberg, K. E., Väliaho, J., Vargas, L., Heinonen, J. E., Berglof, A., Mohamed, A. J., Nore, B. F., Vihinen, M., Smith, C. I. E. 2005. Bruton's tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling. Immunol. Rev. 203:200–215.
Lopéz-Granados, E., Pérez de Diego, R., Ferreira, Cerdán. A., Fontán, Casariego. G., García, Rodríguez. M. C. 2005. A genotype-phenotype correlation study in a group of 54 patients with X-linked agammaglobulinemia. J. Allergy Clin. Immunol. 116:690–697.
Maródi, L., Notarangelo, L. D. 2007. Immunological and genetic bases of new primary immunodeficiencies. Nat. Rev. Immunol. 7:851–61.
Notarangelo, L., Casanova, J. L., Fischer, A., Puck, J., Rosen, F., Seger, R., Geha, R. 2004. Primary immunodeficiency diseases: an update. J. Allergy Clin. Immunol. 114:677–687.
Notarangelo, L. D., Hayward, A. R. 2000. X-linked immunodeficiency with hyper-IgM (XHIM). Clin. Exp. Immunol. 120:399–405.
Notarangelo, L. D., Giliani, S., Mazza, C., Mella, P., Savoldi, G., Rodriguez-Pérez, C., Mazzolari, E., Duse, M., Plebani, A., Ugazio, A. G., Vihinen, M., Candotti, F., Schumacher, R. F. 2000. Of genes and phenotypes: The immunological spectrum of combined immune deficiency. Defects of the γc-JAK3 signaling pathway as a model. Immunol. Rev. 178:39–49.
Ochs, H. H., Smith, C. I. E. and Puck, J. 2006. Primary immunodeficiency disaeses. A molecular and cellular approach. Oxford Univ. Press.
Ortutay, C. and Vihinen, M. 2006. Immunome: a reference set for system biology on the human immune system. Cell. Immunol. 244:87–89.
Ortutay, C., Siermala, M. and Vihinen, M. 2007a. Molecular characterization of the immune system: emergence of proteins, processes and domains. Immunogenet. 59:333–348.
Ortutay, C., Siermala, M. and Vihinen, M. 2007b. ImmTree: database of evolutionary relationships of genes and proteins in the human immune system. Immunome Res. 3:4.
Piirilä, H., Väliaho, J. and Vihinen, M. 2006. Immunodeficiency mutation databases (IDbases). Hum. Mut. 27:1200–1208.
Rannikko, K., Ortutay, C. and Vihinen, M. 2007. Immunity genes and their orthologs: a multi-species database. Int. Immunol. 19:1361–1370.
Riikonen, P., Vihinen M. 1999. MUTbase: maintenance and analysis of distributed mutation databases. Bioinformatics 15:852–859.
Salzer, U., Chapel, H. M., Webster, A. D., Pan-Hammarström, Q., Schmitt-Graeff, A., Schlesier, M., Peter, H. H., Rockstroh, J. K., Schneider, P., Schaffer, A. A., Hammarström, L., Grimbacher, B. 2005. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat. Genet. 37:820–828.
Samarghitean, C., Väliaho, J., Vihinen, M. 2004. Online registry of genetic and clinical immunodeficiency diagnostic laboratories, IDdiagnostics. J. Clin. Immunol. 24:53–61.
Samarghitean, C., Väliaho, J., Vihinen, M. 2007. IDR knowledgebase for primary immunodeficiencies. Immunome Res. 3:6.
Samarghitean, C. and Vihinen, M. 2008. Medical expert systems. Curr. Bioinf. 3:56–65.
Scriver, C. R., Nowacki, P. M., Lehväslaiho, H. 1999. Guidelines and recommendations for content, structure and deployment of mutation databases. Hum. Mut. 13: 344–350.
Väliaho, J., Riikonen, P., Vihinen, M. 2000. Novel immunodeficiency data servers. Immunol. Rev. 178:177–185.
Väliaho, J., Pusa, M., Ylinen, T., Vihinen, M. 2002. IDR: the ImmunoDeficiency Resource. Nucleic Acids Res. 30:232–234.
Väliaho, J., Riikonen, P., Vihinen, M. 2005. Distribution of immunodeficiency fact files with XML – from Web to WAP. BMC Med. Inform. Decis. Mak. 5:21.
Väliaho, J., Smith, C. I. E., Vihinen, M. 2006. BTKbase: mutation database for X-linked agammaglobulinemia. Hum. Mut. 27:1209–1217.
Verpy, E., Biasotto, M., Brai, M., Misiano, G., Meo, T., Tosi, M. 1996. Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angiodema. Am. J. Hum. Genet. 59:308–319.
Vihinen, M., Vetrie, D., Maniar, H. S., Ochs, H. D., Zhu, Q., Vorechovský, I., Webster, A. D., Notarangelo, L. D., Nilsson, L., Sowadski, J. M., Smith, C. I. E. 1994. Structural basis for chromosome X-linked agammaglobulinemia: a tyrosine kinase disease. Proc. Natl. Acad. Sci. USA. 91:12803–12807.
Vihinen, M., Cooper, M. D., de Saint Basile, G., Fischer, A., Good, R. A., Hendriks, R. W., Kinnon, C., Kwan, S. P., Litman, G. W., Notarangelo, L. D., Ochs, H. D., Rosen, F. S., Vetrie, D., Webster, A. D. B., Zegers, B. J. M, Smith, C. I. E. 1995. BTKbase: a database of XLA-causing mutations. Immunol. Today 16:460–465.
Vihinen, M., Durandy, A. 2005. Primary immunodeficiencies: genotype-phenotype correlations. Immunogenomics and human disease (ed. Falus, A.) John Wiley and Sons. pp. 443–460.
Vihinen, M., Kwan, S. P., Lester, T., Ochs, H. D., Resnick, I., Väliaho, J., Conley, M. E., Smith, C. I. E. 1999. Mutations of the human BTK gene coding for Bruton tyrosine kinase in X-linked agammaglobulinemia. Hum. Mutat. 13:280–285.
Vihinen, M., Arredondo-Vega, F. X., Casanova, J. L., Etzioni, A., Giliani, S., Hammarström, L., Hershfield, M. S., Heyworth, P. G., Hsu, A. P., Lähdesmäki, A., Lappalainen, I., Notarangelo, L. D., Puck, J. M., Reith, W., Roos, D., Schumacher, R. F., Schwarz, K., Vezzoni, P., Villa, A., Väliaho, J., Smith, C. I. E. 2001. Primary immunodeficiency mutation databases. Adv. Genet. 43:103–188.
Villa, A., Sobacchi, C., Notarangelo, L. D., Bozzi, F., Abinun, M., Abrahamsen, T. G., Arkwright, P. D., Baniyash, M., Brooks, E. G., Conley, M. E., Cortes, P., Duse, M., Fasth, A., Filipovich, A. M., Infante, A. J., Jones, A., Mazzolari, E., Muller, S. M., Pasic, S., Rechavi, G., Sacco, M. G., Santagata, S., Schroeder, M. L., Seger, R., Strina, D., Ugazio, A., Väliaho, J., Vihinen, M., Vogler, L. B., Ochs, H., Vezzoni, P., Friedrich, W., Schwarz, K. 2001. V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations. Blood 97:81–88.
Acknowledgments
Financial support from Finnish Academy and the Medical Research Fund of Tampere University Hospital is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Vihinen, M. (2009). Immunodeficiencies and Immunome: Diseases and Information Services. In: Falus, A. (eds) Clinical Applications of Immunomics. Immunomics Reviews, vol 2. Springer, New York, NY. https://doi.org/10.1007/978-0-387-79208-8_4
Download citation
DOI: https://doi.org/10.1007/978-0-387-79208-8_4
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-79207-1
Online ISBN: 978-0-387-79208-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)