ICOS Gene Polymorphism May Be Associated with Pemphigus

Abstract

Our results suggest that genetically determined abnormal function of costimulatory receptors in T cells may be associated with the pathogenesis of pemphigus.

Targeting inducible costimulator expressed on CXCR5+PD-1+ TH cells suppresses the progression of pemphigus vulgaris

“…Single cells from spleens and draining lymph nodes of WT skin-grafted Dsg3 -/mice and from spleens of Rag1 -/mice given the various cell populations from WT skin-grafted Dsg3 -/mice were surface-stained at 48C for 20 minutes with the following antibodies: anti-CD3e-BV510 (145-2C11), anti-CD3e-PerCP-Cy5.5 (145-2C11), anti-CD4-APC-Cy7 (GK1.5), anti-CD4-PE-Cy7 (GK1.5), biotin anti-CXCR5 (2G8), anti-CD44-APC-R700 (IM7), anti-CD62L-BB515 (MEL-14), anti-CD19-PE-CF594 (1D3), anti-CD25-BV786 (PC61) anti-B220-BV650 (RA3-6B2), anti-B220-PerCP-Cy5.5 (RA3-6B2), anti-Fas-BV421 (Jo2), anti-Fas-PE-Cy7 (Jo2), anti-GL7-PE (GL7), anti-CD138-APC (281-2), anti-NK1.1-Alexa Fluor 700 (PK136) (all from BD Biosciences); anti-PD-1-BV605 (29F.1A12), anti-PD-1-PE (29F.1A12) (both from BioLegend San Diego, Calif); anti-ICOS-PE-Cy7 (C398.4A), anti-IgD-APC-Cy7 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), and anti-CD3-Alexa Fluor 700 (500A2) (all from Invitrogen). For the staining of human PBMCs the following were used for surface staining at 48C for 20 minutes: anti-CD3-BV786 (SK7), anti-CD4-APC-Cy7 (RPA-T4), biotin anti-CXCR5 (RF8B2), anti-CD45RA-FITC (HI100), anti-CCR7-PE-Cy7 (3D12), anti-CD14-BV510 (M4P-9), anti-CD8-BV510 (SK1), anti-CCR6-APC-R700 (11A9) (all from BD Biosciences); anti-PD-1-BV605 (EH12.2H7) (from BioLegend); anti-CD19-BV510 (HIB19), anti-ICOS-APC (ISA-3) (both from Invitrogen); and anti-CXCR3-PE (49801; R&D Systems).…”

“…14,15 Recently, an anti-ICOS depleting antibody was shown to control systemic sclerosis by reducing ICOS 1 T FH -like cells in the skin. 16 An ICOS polymorphism has also been observed in pemphigus patients; 17,18 however, whether ICOS is expressed in pathogenic T cells and targeting ICOS would control disease activity in pemphigus remain unclear.…”

Beyond the HLA polymorphism: A complex pattern of genetic susceptibility to pemphigus

“…Analysis of a small sample of Polish PV (n = 40) and PF (n = 14) patients showed no statistically significant differences between the patients and the controls for the CTLA4 missense polymorphism rs231775 (+49A>G; Thr17Ala). For ICOS, carriers of the allele C of rs10932029 (IVS1+173T>C) were more frequent between each of both patient samples in comparison with the control sample (Narbutt et al, 2010).…”

CTLA-4 +49 A/G, -318 C/T, -1661 A/G, CT60 A/G Gene Polymorphisms in Patients with Pemphigus in Turkey

“…FernandezMestre et al (16) reported a moderate increase in the +49 G/G genotype in pemphigus and statistically significant increase in +49 G/G genotype and +49 G allele in pemphigus vulgaris (PV) in Venezuelan population. Narbutt et al (17) found no difference in the frequency of genotypes and alleles of +49 A/G CTLA-4 gene polymorphism between the patients with PV and PF with respect to controls in Polish population which point to the differences among populations. The association of a CTLA-4 gene polymorphism with pemphigus in Turkish population has not been studied previously.…”