Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo.

Hdl Handle:
http://hdl.handle.net/10034/604457
Title:
Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo.
Authors:
Augusto, Danillo G.; O'Connor, Geraldine M.; Lobo-Alves, Sara C.; Bass, Sara; Martin, Maureen P.; Carrington, Mary; McVicar, Daniel W.; Petzl-Erler, Maria L.
Abstract:
Although HLA-A3 and A11 have been reported to be ligands for KIR3DL2, evidence for any in vivo relevance of this interaction is still missing. To explore the functional importance of KIR3DL2 allelic variation, we analyzed the autoimmune disease pemphigus foliaceus, previously associated (lower risk) with activating KIR genes. KIR3DL2*001 was increased in patients (odds ratio (OR) = 2.04; p = 0.007). The risk was higher for the presence of both KIR3DL2*001 and HLA-A3 or A11 (OR = 3.76, p = 0.013), providing the first evidence that HLA-A3 and A11 may interact with KIR3DL2 in vivo. The nonsynonymous single nucleotide polymorphism 1190T (rs3745902) was associated with protection (OR = 0.52, p = 0.018). This SNP results in a threonine-to-methionine substitution. Individuals who have methionine in this position exhibit a lower percentage of KIR3DL2-positive natural killer (NK) cells and also lower intensity of KIR3DL2 on expressing natural killer cells; additionally, we show that the expression of KIR3DL2 is independent of other killer cell immunoglobulin-like receptors. Pemphigus foliaceus is a very unique complex disease strongly associated with immune-related genes. It is the only autoimmune disease known to be endemic, showing a strong correlation with environmental factors. Our data demonstrate that this relatively unknown autoimmune disease may facilitate understanding of the molecular mechanisms of KIR3DL2 ligand recognition.
Affiliation:
Departamento de Genética, Universidade Federal do Paraná, Curitiba, PR, Brazil; Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA; Leidos Biomedical Research, Cancer and Inflammation Program, Laboratory for Experimental Immunology, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Citation:
Augusto, D. G., O'Connor, G. M., Lobo-Alves, S. C., Bass, S., Martin, M. P., Carrington, M., . . . Petzl-Erler, M. L. (2015). Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo. European Journal of Immunology, 45(7), 2052-2060. doi: 10.1002/eji.201445324
Publisher:
Wiley
Journal:
European Journal of Immunology
Publication Date:
6-May-2015
URI:
http://hdl.handle.net/10034/604457
DOI:
10.1002/eji.201445324
Additional Links:
http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-4141
Type:
Article
Language:
en
Description:
This is the peer reviewed version of the following article:Augusto, D. G., O'Connor, G. M., Lobo-Alves, S. C., Bass, S., Martin, M. P., Carrington, M., . . . Petzl-Erler, M. L. (2015). Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo. European Journal of Immunology, 45(7), 2052-2060, which has been published in final form at DOI: 10.1002/eji.201445324. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving
EISSN:
1521-4141
Appears in Collections:
Biological Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorAugusto, Danillo G.en
dc.contributor.authorO'Connor, Geraldine M.en
dc.contributor.authorLobo-Alves, Sara C.en
dc.contributor.authorBass, Saraen
dc.contributor.authorMartin, Maureen P.en
dc.contributor.authorCarrington, Maryen
dc.contributor.authorMcVicar, Daniel W.en
dc.contributor.authorPetzl-Erler, Maria L.en
dc.date.accessioned2016-04-05T14:00:23Zen
dc.date.available2016-04-05T14:00:23Zen
dc.date.issued2015-05-06en
dc.identifier.citationAugusto, D. G., O'Connor, G. M., Lobo-Alves, S. C., Bass, S., Martin, M. P., Carrington, M., . . . Petzl-Erler, M. L. (2015). Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo. European Journal of Immunology, 45(7), 2052-2060. doi: 10.1002/eji.201445324en
dc.identifier.doi10.1002/eji.201445324en
dc.identifier.urihttp://hdl.handle.net/10034/604457en
dc.descriptionThis is the peer reviewed version of the following article:Augusto, D. G., O'Connor, G. M., Lobo-Alves, S. C., Bass, S., Martin, M. P., Carrington, M., . . . Petzl-Erler, M. L. (2015). Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo. European Journal of Immunology, 45(7), 2052-2060, which has been published in final form at DOI: 10.1002/eji.201445324. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archivingen
dc.description.abstractAlthough HLA-A3 and A11 have been reported to be ligands for KIR3DL2, evidence for any in vivo relevance of this interaction is still missing. To explore the functional importance of KIR3DL2 allelic variation, we analyzed the autoimmune disease pemphigus foliaceus, previously associated (lower risk) with activating KIR genes. KIR3DL2*001 was increased in patients (odds ratio (OR) = 2.04; p = 0.007). The risk was higher for the presence of both KIR3DL2*001 and HLA-A3 or A11 (OR = 3.76, p = 0.013), providing the first evidence that HLA-A3 and A11 may interact with KIR3DL2 in vivo. The nonsynonymous single nucleotide polymorphism 1190T (rs3745902) was associated with protection (OR = 0.52, p = 0.018). This SNP results in a threonine-to-methionine substitution. Individuals who have methionine in this position exhibit a lower percentage of KIR3DL2-positive natural killer (NK) cells and also lower intensity of KIR3DL2 on expressing natural killer cells; additionally, we show that the expression of KIR3DL2 is independent of other killer cell immunoglobulin-like receptors. Pemphigus foliaceus is a very unique complex disease strongly associated with immune-related genes. It is the only autoimmune disease known to be endemic, showing a strong correlation with environmental factors. Our data demonstrate that this relatively unknown autoimmune disease may facilitate understanding of the molecular mechanisms of KIR3DL2 ligand recognition.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-4141en
dc.subjectNatural Killer Cellsen
dc.subjectKIRen
dc.titlePemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo.en
dc.typeArticleen
dc.identifier.eissn1521-4141en
dc.contributor.departmentDepartamento de Genética, Universidade Federal do Paraná, Curitiba, PR, Brazil; Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA; Leidos Biomedical Research, Cancer and Inflammation Program, Laboratory for Experimental Immunology, Frederick National Laboratory for Cancer Research, Frederick, MD, USA; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.en
dc.identifier.journalEuropean Journal of Immunologyen
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