Abstract
Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are rare autoimmune blistering
diseases with presumed T-cell–dependent pathology. Activation of naïve T cells is
dependent on antigen recognition, subsequent signaling through the T-cell receptor
complex (signal 1), and various other interactions of T cells with antigen presenting
cells that may be collectively designated as signal 2, which is unconditionally required
for T-cell activation both in response to infection and to autoantigens. Among the
best described interactions contributing to signal 2 are those mediated by B7 family
molecules, such as CD80 and CD86 with their ligands; CD28, providing activation signals;
and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), conferring inhibition. Single
nucleotide polymorphisms (SNPs) within genes encoding those molecules may alter the
signaling process. It is not known whether functional genetic polymorphisms within
genes encoding the aforementioned proteins may increase risk for developing PV and
PF and, if so, whether they might serve as biomarkers for susceptibility to these
diseases. To address those questions, we examined functional single nucleotide polymorphisms
within CD86 (rs1129055) and CTLA4 (rs733618 and rs5742909) genes in 61 pemphigus patients and 486 healthy controls.
We found statistically significant differences in allele and genotype frequencies
between PV patients and controls for rs1129055, as well as for rs5742909 among PV
and PF patients. Namely, the rs1129055 A allele was significantly more common in PV
patients compared with controls (35.4% versus 25.7%, respectively; P = .040), whereas the rs5742909 T allele was significantly more common in PF compared
with PV patients (19.2% versus 5.2%, respectively; P = .035). The frequency of the rs5742909 T allele did not, however, differ significantly
in PF or in PV compared with controls (10.5%; P = .187 and P = .100, respectively). We report a novel association of SNPs within CD86 and CTLA4 genes with pemphigus. The CD86 rs1129055 A allele appears to confer susceptibility to PV but not to PF. © 2016 Elsevier
Inc. All rights reserved.
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Article info
Footnotes
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☆☆This study was supported by the Fund of The Serbian Ministry of Education and Science (Grant No 175038). This study was approved by the Ethical Review Board of the School of Medicine University of Belgrade ERB № 29/VI-4 (19. 06. 2013), Ethical Review Board of the Dermatovenereology Clinics of the Clinical Centre of Serbia ERB № 1323 (03.12. 2012), and Ethical Review Board of the National Blood Transfusion Institute ERB № 29/5-15 (18. 11. 2012).
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© 2016 Elsevier Inc. All rights reserved.
