Systemic scleroderma in Greece: low mortality and strong linkage with HLA-DRB1*1104 allele

Vlachoyiannopoulos, P.

doi:10.1136/ard.59.5.359

Cited by 65 publications

(48 citation statements)

References 47 publications

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“…39 of 54 (72%) patients who tested positive for ATA carried these alleles versus ,18% carriership in controls (p50.00006) [84]. Within HLA-DRB1*11, the allelic subtype *1104 seems to be associated with ATA positivity and the presence of lung fibrosis [85]. GILCHRIST et al [84] also showed that HLA DPB1*1301 was tightly associated with ATA presence.…”

Section: Pulmonary Fibrosis In Systemic Sclerosismentioning

confidence: 91%

“…Major histocompatibility complex Strong associations have been found between HLA-DRB1*11, and also HLA-DPB1*1301, and diffuse systemic sclerosis, and there is some evidence to suggest that it is an amino-acid motif, shared by the different class II susceptibility alleles, that may be pivotal in predisposing to autoantibody formation [84,85].…”

Section: Pulmonary Fibrosis In Systemic Sclerosismentioning

confidence: 99%

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Genetics of fibrosing lung diseases

Grutters

Bois²

2005

Eur Respir J

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Genetic studies in familial lung fibrosis have demonstrated an association with surfactant protein C genes: two mutations have been found resulting in protein misfolding and causing type-II epithelial cell injury. Remarkably, different histological patterns were observed in the affected subjects, suggesting the influence of modifier genes and/or environmental factors. Surfactant protein C gene variations have not, however, been associated with sporadic cases,i.e.idiopathic pulmonary fibrosis (IPF).Susceptibility to IPF probably involves a combination of polymorphisms related to epithelial cell injury and abnormal wound healing. To date, the genetic associations with IPF that have been reported in different cohorts include the genes encoding tumour necrosis factor (TNF; −308 adenine), interleukin-1 receptor antagonist (+2018 thymidine) and association with severity and progression (interleukin-6/TNF receptor II and transforming growth factor-β1 (TGFB1; +869 cytosine)), but none of these associations have been replicated by others.Unlike in IPF, immunological inflammation seems to be more prominent in the pathogenesis of scleroderma lung fibrosis, being an autoimmune disease with specific autoantibodies, such as antitopoisomerase antibodies, in patients with diffuse lung disease, and anticentromere antibodies, in patients with pulmonary vascular disease. Antitopoisomerase antibody positivity is associated with the carriage of human leukocyte antigen DRB1*11 and DPB1*1301 alleles, suggesting the recognition of a specific amino-acid motif. Extended haplotype analysis also supports the conclusion that TNF may be the primary association with anticentromere positivity. Intriguingly, associations with TGFB1 and genes involved in extracellular matrix homeostasis have been reported in this disease.In conclusion, significant steps forward have been taken in the understanding of the genetic contribution to fibrosing lung diseases, but major challenges lay ahead. It is the present authors' opinion that only a combined approach studying large numbers of familial and sporadic cases, all clinically well phenotyped, using multiple distinct cohorts, and genotyped according to relevant gene ontologies will be successful. It will be necessary to be particularly vigilant with regard to phenotype; the absence of very strong reproducible associations may be because of the rigidity of phenotype definition, coupled with the possibility that idiopathic pulmonary fibrosis may still be a heterogeneous group of diseases, despite the more rigid definition set out by the European Respiratory Society/American Thoracic Society statement.

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Section: Pulmonary Fibrosis In Systemic Sclerosismentioning

confidence: 91%

Section: Pulmonary Fibrosis In Systemic Sclerosismentioning

confidence: 99%

Genetics of fibrosing lung diseases

Grutters

Bois²

2005

Eur Respir J

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“…It is worth mentioning that none of the patients with RP expressed HLA-DRB1*04 and -DQB1*0302 alleles, which are also in linkage disequilibrium in the Greek population [27]. The above-mentioned negative association may define a protective haplotype against RP, a condition already noticed in several autoimmune diseases [27,28]. …”

Section: Discussionmentioning

confidence: 99%

The Role of the Immunogenetic Background in the Development and Recurrence of Acute Idiopathic Pericarditis

Lazaros

Karavidas²,

Spyropoulou³

et al. 2011

Cardiology

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Objectives: We assessed the role of the immunogenetic background in the development and recurrence of acute idiopathic pericarditis (AIP). Methods: Fifty-five patients with a first episode of AIP were followed for 23.8 ± 6.3 months and recurrences were recorded. The control group consisted of 246 healthy individuals. In all subjects, genomic human leukocyte antigen (HLA) typing was performed. Moreover, circulating lymphocyte subpopulations were studied in 44 randomly selected patients and in 20 controls. Results: An increased frequency of HLA-A*02, -Cw*07 and -DQB1*0202 alleles, and a decreased frequency of the -DQB1*0302 allele was detected in patients with AIP. The recurrence rate was 40% and time to recurrence was 202.8 ± 164.1 days. In patients with idiopathic recurrent pericarditis (RP), increased frequencies of HLA-A*02, -Cw*07 and -DQB1*0202 alleles were found. Notably, no patient with RP exhibited HLA-DRB1*04 and -DQB1*0302 alleles. Patients with RP exhibited lower CD4+/CD45RA+ naïve T cells (p = 0.03) than controls, and higher CD8+DR+ activated T cells (p = 0.01) than patients without recurrence and controls. Conclusions: HLA alleles may confer either susceptibility or resistance to AIP and RP. Circulating T-cell subpopulations may also predict RP. A combination of the above parameters might help to better define patients prone to recurrence.

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“…5 Systemic sclerosis is found to be strongly associated with HLA-DRB1*1104 allele in the Greek community. 6 …”

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confidence: 97%

Takayasu arteritis associated with systemic sclerosis

et al. 2006

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Takayasu arteritis (TA), or pulselessness disease, is a necrotizing and obliterative giant cell arteritis whose etiology is unknown; it involves the aorta and its main branches, and coronary and pulmonary arteries. It is diagnosed by clinical findings and angiographic investigation. 1 Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology. Its vasculopathy is manifested by abnormal collection of collagen and extracellular matrix in skin and internal organs, and is caused by immunologic mechanisms. 1 Causes of TA associated with SSc are rarely found. 2 We report the case of a patient with TA who developed SSc 1 year later. This is the third case of Takayasu arteritis associated with systemic sclerosis reported in the literature.A 48-year-old female patient was admitted to our clinic with complaints of malaise and cyanosis on the fingertips, especially in cold environments. One year previously a physical examination for intermittent claudication had shown that she had no pulse on the distal arms. Doppler ultrosonographic investigation showed 85% and 75% narrowing of the right and left subclavian arteries, respectively. The narrowing showed that the left and right subclavian arteries were obliterated on the distal side of the vertebral artery bifurcation region (Fig. 1). Angiographic investigation of the lower extremities revealed that visualization was not possible for the right dorsal pedal artery, the 1/3 distal side of left tibial anterior artery, and the left dorsal pedal artery. The patient was diagnosed as having TA. She had a 3-year history of Raynaud phenomenon in her medical record. Physical examination showed that her blood pressure was 150/70 mmHg on right thigh, pulse rate rhythm 74/min, and upper extremity pulses could not be palpated. There was no murmur on the vessels of the neck. There were dermal indurations on the proximal metacarpopharyngeal joints and fingers of both hands. There were no abnormalities on the other systemic organs.

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Systemic scleroderma in Greece: low mortality and strong linkage with HLA-DRB1*1104 allele

Cited by 65 publications

References 47 publications

Genetics of fibrosing lung diseases

Genetics of fibrosing lung diseases

The Role of the Immunogenetic Background in the Development and Recurrence of Acute Idiopathic Pericarditis

Takayasu arteritis associated with systemic sclerosis

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