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

Beretta, Lorenzo; Rueda, Blanca; Marchini, Maurizio; Santaniello, Alessandro; Simeón, Carmen P.; Fonollosa, V.; Caronni, Monica; Ríos-Fernández, Raquel; Carreira, Patrícia; Rodríguez‐Rodríguez, Luis; Moreno, Antonia Ruíz; López–Nevot, Miguel A.; Escalera, Ana Marı́a Anaya; González‐Escribano, María Francisca; Martín, Javier; Scorza, Raffaella

doi:10.1093/rheumatology/ker335

Cited by 49 publications

(43 citation statements)

References 28 publications

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“…However, for the Hispanic populations, HLA-DRB1*1104 was the allele that showed the most significant association and the highest OR for this autoantibody. Interestingly, previous studies have also correlated HLA-DRB1*11 with ATA-positive status in whites, blacks and Hispanics [11,21,22]. The analyses performed in the ACA-positive subset of patients revealed an over-representation of the HLA-DQB1*0501 and HLA-DQB1*26 epi alleles in white population.…”

Section: Hlamentioning

confidence: 68%

“…The analyses performed in the ACA-positive subset of patients revealed an over-representation of the HLA-DQB1*0501 and HLA-DQB1*26 epi alleles in white population. Additionally, significant associations with HLA-DRB1*01, HLA-DRB1*04 and HLA-DRB1*08 have also been reported [11,21,22]. The anti-RNA polymerase III antibody positive SSc patient subset was explained by HLA-DRB1*0404, HLA-DRB1*11 and HLA-DQB1*03 in Caucasian and Hispanic populations [20].…”

Section: Hlamentioning

confidence: 87%

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Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways

Bossini‐Castillo

López‐Isac

Martı́n

2015

Journal of Autoimmunity

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Section: Hlamentioning

confidence: 68%

Section: Hlamentioning

confidence: 87%

Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways

Bossini‐Castillo

López‐Isac

Martı́n

2015

Journal of Autoimmunity

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“…Moreover, these HLA alleles not only determine SSc susceptibility, several studies also showed that some of them have a protective effect. It should also be noted that these associations can be common in different ethnicities, while others are specific to certain populations [24, 25]. The first GWAS in SSc reported that a SNP located in HLA-DQB1 had the strongest association [18].…”

Section: Genetic Involvementmentioning

confidence: 99%

Unfolding the pathogenesis of scleroderma through genomics and epigenomics

Tsou

Sawalha

2017

Journal of Autoimmunity

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With unknown etiology, scleroderma (SSc) is a multifaceted disease that comprises of immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated. The non-HLA genes associated with SSc are involved in various functions, with the most robust associations including genes for B and T cell activation and innate immunity. Other pathways include genes involved in extracellular matrix deposition, cytokines, and autophagy. Among these genes, IRF5, STAT4, and CD247 were replicated most frequently while SNPs rs35677470 in DNASE1L3, rs5029939 in TNFAIP3, and rs7574685 in STAT4 have the strongest associations with SSc. In addition to genetic predisposition, it became clear that environmental factors and epigenetic influences also contribute to the development of SSc. Epigenetics, which refers to studies that focus on heritable phenotypes resulting from changes in chromatin structure without affecting the DNA sequence, is one of the most rapidly expanding fields in biomedical research. Indeed extensive epigenetic changes have been described in SSc. Alteration in enzymes and mediators involved in DNA methylation and histone modification, as well as dysregulated miRNA levels all contribute to fibrosis, immune dysregulation, and impaired angiogenesis in this disease. Genes that were affected by epigenetic dysregulation include ones involved in autoimmunity, T cell function and regulation, TGFβ pathway, Wnt pathway, extracellular matrix, and transcription factors governing fibrosis and angiogenesis. In this review, we provide a comprehensive overview of the current findings of SSc genetic susceptibility, followed by an extensive description and a systematic review of epigenetic research that has been carried out to date in SSc. We also summarize the therapeutic potential of drugs that affect epigenetic mechanisms, and outline the future prospective of genomincs and epigenomics research in SSc.

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“…Class I (HLA A, B, and C) and class II (HLA DR, DQ, and DP) molecules are expressed on the cell surface and participate in antigen presentation and T lymphocyte activation. Class I molecules also activate natural killer (NK) cell receptors [11], and class II molecules appear to stimulate the secretion of IL-6 and monocyte chemotactic protein (MCP-1) by fibroblasts, especially in antibody antitopoisomerase (ATA) associated clinical forms [12]. …”

Section: Introductionmentioning

confidence: 99%

“…Caucasian patients were associated with HLA-DR5 [23–25], corresponding to DRB1*05, and Japanese patients were associated with HLA-DR2 [5], DRB1*15, or DRB1*16 in the current nomenclature. The anticentromere antibody (ACA) was related to the HLA-DRB1*01, DRB1*04, DQA1*0101, and DQB1*0501 alleles [7, 12, 13, 23]. …”

Section: Introductionmentioning

confidence: 99%

HLA Markers for Poor Prognosis in Systemic Sclerosis Brazilian Patients

et al. 2013

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Objectives. The aim of this study was to evaluate human leukocyte antigen (HLA) involvement in the disease expression and poor prognostic clinical features (pulmonary fibrosis and pulmonary arterial hypertension) in patients diagnosed with systemic sclerosis (SSc) in a multiethnic population. Methods. SSc patients followed up between 2008 and 2011 were included, and clinical data were obtained through records review. Molecular HLA typing was performed (polymerase chain reaction amplification technique using specific primer sequences). The statistical analysis involved Fisher's exact test and Pearson's corrected chi-square test. P values ≤ 0.05 were considered significant. The delta method was used to estimate the variance of the prevalence ratio (PR). Results. A total of 141 patients (120 women and 21 men) with SSc were studied, including 33.3% with diffuse cutaneous SSc (dcSSc), 62.4% with limited cutaneous SSc (lcSSc), and 4.3% with sine scleroderma. Pulmonary fibrosis was present in 61 patients (43.3%), and the HLA-A∗30 and DQB1∗04 alleles were related to susceptibility. In contrast, the HLA-DRB1∗01 and DQB1∗05 alleles were protective. Pulmonary arterial hypertension was diagnosed in 19 patients (13.5%) and was associated with HLA-B∗35 and C∗04; in contrast, C∗03 seemed to be protective. Conclusions. Our current study documents the association of some classes I and II HLA alleles with the most severe clinical manifestations in a multiethnic case series. Our findings differed slightly from the previous data in other populations.

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

Abstract: We describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc.

Cited by 49 publications

References 28 publications

Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways

Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways

Unfolding the pathogenesis of scleroderma through genomics and epigenomics

HLA Markers for Poor Prognosis in Systemic Sclerosis Brazilian Patients

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