Dataset Information

Analysis of Class II human leucocyte antigens in Italian and Spanish systemic sclerosis.

ABSTRACT:

Objective

To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry.

Methods

Nine hundred and forty-four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA-DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I-positive subjects. Associations between SSc or SSc-specific antibodies and HLA alleles or HLA haplotypes were sought via the chi-square test after 10?000-fold permutation testing. A meta-analysis including this study cohort and other Caucasoids samples was also conducted.

Results

In both the cohorts, the strongest association was observed between the HLA-DRB1*1104 allele and SSc or anti-topo I antibodies. The HLA-DRB1*1104 -DQA1*0501 -DQB1*0301 haplotype was overrepresented in Italian [odds ratio (OR)?=?2.069, 95% asymptotic CIs (CI(95)) 1.486, 2.881; P?ConclusionsWe describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc.

SUBMITTER: Beretta L

PROVIDER: S-EPMC3276293 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysis of Class II human leucocyte antigens in Italian and Spanish systemic sclerosis.

Beretta Lorenzo L Rueda Blanca B Marchini Maurizio M Santaniello Alessandro A Simeón Carmen P CP Fonollosa Vicente V Caronni Monica M Rios-Fernandez Raquel R Carreira Patricia P Rodriguez-Rodriguez Luis L Moreno Antonia A López-Nevot Miguel A MA Escalera Ana A González-Escribano Maria F MF Martin Javier J Scorza Raffaella R

Rheumatology (Oxford, England) 20111115 1

<h4>Objective</h4>To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry.<h4>Methods</h4>Nine hundred and forty-four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA-DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I-positi ...[more]

PMID: 22087014

Similar Datasets

Project description:JC polyomavirus (JCV) carriers with a compromised immune system, such as in HIV, or subjects on immune-modulating therapies, such as anti VLA-4 therapy may develop progressive multifocal leukoencephalopathy (PML) which is a lytic infection of oligodendrocytes in the brain. Serum antibodies to JCV mark infection occur only in 50-60% of infected individuals, and high JCV-antibody titers seem to increase the risk of developing PML. We here investigated the role of human leukocyte antigen (HLA), instrumental in immune defense in JCV antibody response. Anti-JCV antibody status, as a surrogate for JCV infection, were compared to HLA class I and II alleles in 1621 Scandinavian persons with MS and 1064 population-based Swedish controls and associations were replicated in 718 German persons with MS. HLA-alleles were determined by SNP imputation, sequence specific (SSP) kits and a reverse PCR sequence-specific oligonucleotide (PCR-SSO) method. An initial GWAS screen displayed a strong HLA class II region signal. The HLA-DRB1*15 haplotype was strongly negatively associated to JCV sero-status in Scandinavian MS cases (OR?=?0.42, p?=?7×10(-15)) and controls (OR?=?0.53, p?=?2×10(-5)). In contrast, the DQB1*06:03 haplotype was positively associated with JCV sero-status, in Scandinavian MS cases (OR?=?1.63, p?=?0.006), and controls (OR?=?2.69, p?=?1×10(-5)). The German dataset confirmed these findings (OR?=?0.54, p?=?1×10(-4) and OR?=?1.58, p?=?0.03 respectively for these haplotypes). HLA class II restricted immune responses, and hence CD4+ T cell immunity is pivotal for JCV infection control. Alleles within the HLA-DR1*15 haplotype are associated with a protective effect on JCV infection. Alleles within the DQB1*06:03 haplotype show an opposite association. These associations between JC virus antibody response and human leucocyte antigens supports the notion that CD4+ T cells are crucial in the immune defence to JCV and lays the ground for risk stratification for PML and development of therapy and prevention.

Dataset Information

Analysis of Class II human leucocyte antigens in Italian and Spanish systemic sclerosis.

Objective

Methods

Results

Publications

Analysis of Class II human leucocyte antigens in Italian and Spanish systemic sclerosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets