Severe Pulmonary Sarcoidosis Is Strongly Associated With the Haplotype HLA-DQB1*0602–DRB1*150101

Voorter, Christina E.M.; Drent, Marjolein; Berg‐Loonen, Ella M. van den

doi:10.1016/j.humimm.2005.04.003

Cited by 76 publications

(66 citation statements)

References 37 publications

(47 reference statements)

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“…As expected, many of the genes or products of genes overexpressed in sarcoidosis participate in Th1-type antigen responses, including HLA-DRB1, which has been specifically linked to the pathogenesis of sarcoidosis (46,47). The most significant finding of this analysis was the identification of highly interactive gene networks, which regulate the expression of granuloma-promoting signaling proteins (STAT1), inflammatory cytokines (IL-7, IL-15), and proteolytic enzymes (MMP-12, ADAMDEC1), that are operating within the lung compartment of patients with sarcoidosis.…”

Section: Mmp12supporting

confidence: 62%

Gene Expression Profiling Identifies MMP-12 and ADAMDEC1 as Potential Pathogenic Mediators of Pulmonary Sarcoidosis

Crouser¹,

Culver²,

Knox³

et al. 2009

Am J Respir Crit Care Med

132

126

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Section: Mmp12supporting

confidence: 62%

Gene Expression Profiling Identifies MMP-12 and ADAMDEC1 as Potential Pathogenic Mediators of Pulmonary Sarcoidosis

Crouser¹,

Culver²,

Knox³

et al. 2009

Am J Respir Crit Care Med

132

126

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“…Initial chest x-ray revealed more advanced disease in HLA-DRB1*014 and HLA-DRB1*015 positive patients. Previous studies revealed that HLA-DRB allels played a crucial role for many aspects of sarcoidosis [9,10,[17][18][19][20]. Prognosis and outcome of sarcoidosis predominantly depends upon the specific HLA profile of the patient.…”

Section: Discussionmentioning

confidence: 99%

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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“…In addition to disease susceptibility, variation at DRB1 is associated with organspecific involvement (7,11) and disease course (3,8,9,(15)(16)(17). The allele DRB1*03 belongs to the European-derived "8.1 ancestral haplotype," made up primarily of *03:01 carriers (18).…”

mentioning

confidence: 99%

Association of HLA-DRB1 with Sarcoidosis Susceptibility and Progression in African Americans

Levin¹,

Adrianto

Iannuzzi

et al. 2015

Am J Respir Cell Mol Biol

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HLA-DRB1 is a sarcoidosis risk gene, and the *03:01 allele is strongly associated with disease resolution in European sarcoidosis cases. Whereas the HLA-DRB1 variation is associated with sarcoidosis susceptibility in African Americans, DRB1 risk alleles are not as well defined, and associations with disease resolution have not been studied. Associations between genotyped and imputed HLA-DRB1 alleles and disease susceptibility/resolution were evaluated in a sample of 1,277 African-American patients with sarcoidosis and 1,467 control subjects. In silico binding assays were performed to assess the functional significance of the associated alleles. Increased disease susceptibility was associated with the HLA-DRB1 alleles *12:01 (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.65-2.69; P = 3.2 3 10 29 ) and *11:01 (OR, 1.69; 95% CI, 1.42-2.01; P = 3.0 3 10 29 ). The strongest protective association was found with *03:01 (OR, 0.56; 95% CI, 0.44-0.73; P = 1.0 3 10 25 ). The African-derived allele *03:02 was associated with decreased risk of persistent radiographic disease (OR, 0.52; 95% CI, 0.37-0.72; P = 1.3 3 10 24 ), a finding consistent across the three component studies comprising the analytic sample. The DRB1*03:01 association with disease persistence was dependent upon local ancestry, with carriers of at least one European allele at DRB1 at a decreased risk of persistent disease (OR, 0.36; 95% CI, 0.14-0.94; P = 0.037). Results of in silico binding analyses showed that DRB1*03:01 consistently demonstrated the highest binding affinities for six bacterial peptides previously found in sarcoidosis granulomas, whereas *12:01 displayed the lowest binding affinities. This study has identified DRB1*03:01 and *03:02 as novel alleles associated with disease susceptibility and course in African Americans. Further investigation of DRB1*03 alleles may uncover immunologic factors that favor sarcoidosis protection and resolution among African Americans.

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Severe Pulmonary Sarcoidosis Is Strongly Associated With the Haplotype HLA-DQB10602–DRB1150101

Cited by 76 publications

References 37 publications

Gene Expression Profiling Identifies MMP-12 and ADAMDEC1 as Potential Pathogenic Mediators of Pulmonary Sarcoidosis

Gene Expression Profiling Identifies MMP-12 and ADAMDEC1 as Potential Pathogenic Mediators of Pulmonary Sarcoidosis

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

Association of HLA-DRB1 with Sarcoidosis Susceptibility and Progression in African Americans

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