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

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.
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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.
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2015-05-06
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Biological Sciences
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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.
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
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Wiley
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European Journal of Immunology
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http://hdl.handle.net/10034/604457
DOI
10.1002/eji.201445324
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Article
Language
en
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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
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1521-4141
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http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1521-4141
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