High prevalence of familial sarcoidosis in an Irish population.

Brennan, Niamh; Crean, P.; Long, Jun; Fitzgerald, M. X.

doi:10.1136/thx.39.1.14

Cited by 73 publications

(34 citation statements)

References 15 publications

(3 reference statements)

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“…Environmental, humoral, and hormonal factors may also play a role in the chronic and persistent disease. It is a well-known fact that the occasional occurrence of sarcoidosis in the first-degree relatives and identical twins suggests that genetic predisposition plays the most important role in the pathogenesis and thereby in the variable clinical manifestations of sarcoidosis [5,15,16]. The genetic background of sarcoidosis patients described by the HLA typing in clinical practice appears to be the most crucial factor determining the variable outcome of sarcoidosis for the individual patient is the most relevant finding of this study.…”

Section: Discussionsupporting

confidence: 49%

Association of HLA antigens with the clinical course of sarcoidosis and familial disease

Yanardağ

Tetikkurt

Bilir

et al. 2017

Monaldi Arch Chest Dis

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Patients with sarcoidosis usually have a benign course and a favourable prognosis. Although spontaneous remission is common, a progressive disease with a severe prognosis occurs in a small but significant number of patients. The aim of this study was to evaluate the potential significance of HLA antigens as a clinical marker on the outcome of sarcoidosis patients. We conducted a retrospective cohort study for HLA class I and II allels in 74 sarcoidosis patients and 72 healthy transplant donors. Bronchoscopy and bronchial biopsies were performed in each patient.

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Section: Discussionsupporting

confidence: 49%

Association of HLA antigens with the clinical course of sarcoidosis and familial disease

Yanardağ

Tetikkurt

Bilir

et al. 2017

Monaldi Arch Chest Dis

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“…Cumulative incidence estimates predict a lifetime risk of sarcoidosis of 0.85 and 2.4% for U.S. whites and blacks, respectively (3). Familial clustering of the disease has provided evidence that genetic predisposition may be an important risk factor, with loci that influence T cell function, regulation of Ag recognition, and processing or regulation of matrix deposition and granuloma formation representing the most likely candidate genes (4,5). In particular, individuals with specific HLA-DR genotypes appear to be at higher risk (6 -10).…”

mentioning

confidence: 99%

Role of IL-18 in CD4+ T Lymphocyte Activation in Sarcoidosis

Greene

Meachery

Taggart

et al. 2000

The Journal of Immunology

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Sarcoidosis is a granulomatous disease of unknown etiology associated with the expansion of IL-2-producing activated CD4+ T lymphocytes. A number of factors including the recently described IL-18 have been implicated in IL-2 expression in vitro. We investigated the role of IL-18 in IL-2 expression in sarcoidosis. Eighteen individuals with sarcoidosis and 15 normal controls were studied. IL-18R expression and epithelial lining fluid (ELF) concentrations of IL-18 were significantly elevated in the sarcoid group (p = 0.0143 and 0.0024, respectively). Both AP1 and NF-κB, transcription factors that regulate IL-2 gene expression, were activated in vivo in sarcoid pulmonary CD4+ T lymphocytes. Transcription factor activity was not detected in pulmonary CD4+ T lymphocytes from normal controls or from peripheral blood CD4+ T lymphocytes from individuals with sarcoidosis, further evidence of compartmentalization of the lymphoproliferative process in this condition. We examined the effects of IL-18 on AP1 and NF-κB in Jurkat T cells in vitro. These effects were both time and dose dependent. Examination of transcription factor activation and IL-2 gene expression in Jurkat T cells revealed that sarcoid but not normal ELF activated AP1 and NF-κB, induced IL-2 gene transcription, and up-regulated IL-2 protein production. Addition of IL-18 to normal ELF also induced IL-2 mRNA accumulation, whereas correspondent depletion of IL-18 from sarcoid ELF using neutralizing Abs abrogated all of the effects. These data strongly implicate IL-18 in the pathogenesis of sarcoidosis via activation of AP1 and NF-κB, leading to enhanced IL-2 gene expression and IL-2 protein production and concomitant T cell activation.

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“…[3][4][5][6][7][8][9] In the UK report a total of nine families from a series of 537 patients were identified giving a prevalence of 1.7% for familial sarcoidosis. This study also showed a preponderance of monozygous over dizygous twins, like-sex over unlike-sex pairs, and mother-child over father-child associations in these families.…”

mentioning

confidence: 99%

Epidemiology of familial sarcoidosis in the UK

McGrath

2000

Thorax

109

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Background-The last comprehensive epidemiological studies on familial sarcoidosis in the UK were more than 25 years ago, reporting another aVected family member in 1.7% of index cases. A significant proportion of like-sex over unlike-sex pairs, an excess of mother-child over father-child associations, and a preponderance of monozygous over dizygous twins was noted. Another study reported ethnic heterogeneity in familial disease. This study was undertaken to identify the risk ratio ( S ) for siblings of familial sarcoidosis in the UK, to determine if the previous epidemiological findings have persisted, and to reassess whether ethnic heterogeneity prevails in familial disease. Method-Questionnaires were sent to 406 index patients. Results-Two hundred and sixty eight replies (66%) were received. Twenty four of the original 406 index patients (5.91%) were found to have at least one other relative (first, second or third degree) with biopsy proven sarcoidosis. A S value of 36-73 was calculated indicating significant familial clustering of the disease. Ethnically the families comprised 62.5% Caucasian, 29.2% Afro-Caribbean, and 8.3% Asian. Mean age at diagnosis was 39.8 years for women and 40.9 years for men with a male to female ratio of 1:1.7. This diVered for the Asian families in which all the aVected members were male. Three sets of female twins (two monozygous and one dizygous) were included. There was an equal distribution of like-sex (primarily female) and unlike-sex families as well as mother-child and father-child pairs. Pulmonary involvement was predominant irrespective of ethnicity, as was the need for corticosteroid treatment. Conclusions-These results support the theory that a shared determinant (either genetic or environmental) is operating in familial sarcoidosis and suggest that this determinant is similar for all ethnic groups.

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High prevalence of familial sarcoidosis in an Irish population.

Cited by 73 publications

References 15 publications

Association of HLA antigens with the clinical course of sarcoidosis and familial disease

Association of HLA antigens with the clinical course of sarcoidosis and familial disease

Role of IL-18 in CD4+ T Lymphocyte Activation in Sarcoidosis

Epidemiology of familial sarcoidosis in the UK

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