Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA‐A3 and A11 in vivo. Issue 7 (6th May 2015)

• Record Type: Journal Article
• 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 Luiza
• Is Part Of: European journal of immunology. Volume 45:Issue 7(2015:Jul.)
• Page Start: 2052
• Page End: 2060
• Publication Date: 2015-05-06
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201445324
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>KIR3DL2</italic> allelic variation, we analyzed the autoimmune disease pemphigus foliaceus, previously associated (lower risk) with activating <italic>KIR</italic> genes. <italic>KIR3DL2*001</italic> was increased in patients (odds ratio (OR) = 2.04; <italic>p</italic> = 0.007). The risk was higher for the presence of both <italic>KIR3DL2*001</italic> and HLA‐A3 or A11 (OR = 3.76, <italic>p</italic> = 0.013), providing the first evidence that HLA‐A3 and A11 may interact with KIR3DL2 in vivo. The nonsynonymous single nucleotide polymorphism <italic>1190T</italic> (<italic>rs3745902</italic>) was associated with protection (OR = 0.52, <italic>p</italic> = 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.</p> </abstract>