Major histocompatibility complex class II and<i>BTNL2</i>associations in sarcoidosis

Wennerström, Annika; Pietinalho, Anne; Lasota, Jagoda; Salli, Krista; Surakka, Ida; Seppänen, Mikko; Selroos, Olof; Lokki, Marja-Liisa

doi:10.1183/09031936.00035213

Cited by 24 publications

(22 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, our study adds the original findings that although BTNL2 polymorphism was strongly associated with the disease, its presence was not predictive of the development of a rather familial or rather sporadic case and not associated with the clinical phenotypes, the SCAC, or the outcome. This result differs from others that suggested that BTNL2 might be a predisposing factor for persistent or progressive sarcoidosis [10, 21, 22]. Our data may be interpreted in the light of the low OR of BTNL2 rs2076530 (=2) we found; that is, the BTNL2 gene is not an explanatory factor of disease inheritance.…”

Section: Discussioncontrasting

confidence: 99%

“…Here, we cannot exclude that the BTNL2-sarcoidosis association we observed is the consequence of gene proximity in the 6p21 area with a synergistic effect of some HLA class II haplotypes and the truncated form of BTNL2 on T-cell activation and proliferation process [22, 25]. Actually, one limitation of the present study is the lack of extensive screening for HLA-DRB1/DPB1 in the patients.…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Familial vs. sporadic sarcoidosis: BTNL2 polymorphisms, clinical presentations, and outcomes in a French cohort

Pachéco¹,

Calender²,

Israël‐Biet³

et al. 2016

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundThe occurrence of familial forms of sarcoidosis (OMIM 181100) suggests a genetic predisposition. The involvement of butyrophilin-like 2 (BTNL2) gene (rs2076530 variant) has to be investigated.ResultsThe study performed independent analyses of BTNL2 polymorphism, clinical phenotypes, and outcomes in familial vs. sporadic presentations in 256 sporadic and 207 familial cases from 140 families. The logistic multivariate model showed that a young age at diagnosis and the combination of lung and skin involvement at diagnosis may distinguish sporadic from familial sarcoidosis (p = 0.016 and p = 0.041). We observed also that Sarcoid Clinical Activity Classification (SCAC) profiles were significantly different between familial and sporadic cases (p = 0.0497).Variant rs2076530 was more frequent in patients than in controls (OR = 2.02; 95% CI: [1.32–3.09]) but showed no difference between sporadic and familial cases and no difference according to the clinical phenotype or the outcome.ConclusionDespite a significant difference in BTNL2 polymorphism between sarcoid patients and controls, there was no such difference between familial and sporadic sarcoidosis cases and no correlation between BTNL2 polymorphism and disease severity or outcome. Thus, BTNL2 difference cannot be considered as a key marker for disease classification or patient management.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 90%

Familial vs. sporadic sarcoidosis: BTNL2 polymorphisms, clinical presentations, and outcomes in a French cohort

Pachéco¹,

Calender²,

Israël‐Biet³

et al. 2016

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…Two review articles were eliminated [24,39] ; 1 article was not included because it was not designed as a case–control study. [40] Two articles did not extract the available data to further count the pooled OR and 95% CI [41,42] ; 1 article was excluded because it mainly included family members of patients with sarcoidosis rather than healthy people in the control group, and 1 article was repeated. [43] Thus, all 15 articles were identified.…”

Section: Resultsmentioning

confidence: 99%

The BTNL2 G16071A gene polymorphism increases granulomatous disease susceptibility

Xiang

Niu

et al. 2016

Medicine

View full text Add to dashboard Cite

Objective:The butyrophilin-like 2 (BTNL2) G16071A gene polymorphism has been implicated in the susceptibility to granulomatous diseases, but the results were inconclusive. The objective of the current study was to precisely explore the relationship between BTNL2 G16071A gene polymorphism and granulomatous disease susceptibility by the meta-analysis including false-positive report probability (FPRP) test.Methods:A systematic literature search in the PubMed, Embase, and Wanfang databases, China National Knowledge Internet, and commercial Internet search engines was conducted to identify studies published up to April 1, 2016. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the effect size. Statistical analysis was conducted using the STATA 12.0 software and FPRP test sheet.Results:In total, all 4324 cases and 4386 controls from 14 eligible studies were included in the current meta-analysis. By the overall meta-analysis, we found a significant association between BTNL2 G16071A gene polymorphism and granulomatous disease susceptibility (A vs G: OR = 1.25, 95% CI = 1.07–1.45, P = 0.005). The meta-regression analyses showed that a large proportion of the between-study heterogeneity was significantly attributed to the ethnicity (A vs G, P = 0.013) and the types of granulomatous diseases (A vs G, P = 0.002). By the subgroup meta-analysis, the BTNL2 G16071A gene polymorphism was associated with granulomatous disease susceptibility in Caucasians (A vs G: OR = 1.37, 95% CI = 1.18–1.58, P < 0.001). Moreover, a significant relationship between the BTNL2 G16071A gene polymorphism and sarcoidosis susceptibility (A vs G: OR = 1.52, 95% CI = 1.39–1.66, P < 0.001) was found. However, to avoid the “false-positive report,” we further investigated the significant associations observed in the present meta-analysis by the FPRP test. Interestingly, the results of FPRP test indicated that the BTNL2 G16071A gene polymorphism was truly associated with sarcoidosis susceptibility (A vs G, FPRP < 0.001). Additionally, the FPRP test confirmed that the BTNL2 G16071A gene polymorphism was associated only with granulomatous disease susceptibility among Caucasians (A vs G, FPRP < 0.001) at the level of a prior probability, which was 0.001.Conclusion:The meta-analysis indicated that BTNL2 G16071A gene polymorphism may as a likelihood factor contributed to granulomatous disease susceptibility, especially increasing the sarcoidosis susceptibility. In addition, the polymorphism may be greatly associated with likelihood of granulomatous diseases among Caucasians.

show abstract

“…In mice, it was shown that BTNL2 controls mucosal inflammation by promoting FOXP3 expression and thereby the development of regulatory T cells 34 . The genetic association of the BTNL2 variant with sarcoidosis has been confirmed in various populations, including African Americans and Japanese 17, 35-41 . Most recently, the association was confirmed in a Greek population of 146 sarcoidosis patients and 90 controls 42 .…”

Section: Introductionmentioning

confidence: 89%

Granuloma genes in sarcoidosis

Fischer

Rybicki

2015

Current Opinion in Pulmonary Medicine

View full text Add to dashboard Cite

Purpose of review Non-necrotizing granulomas in the affected organ are the hallmark of sarcoidosis. This review summarizes most recent genetic findings in sarcoidosis with a focus on genes that might influence granuloma formation or resolution. Specific results in multiple ethnic groups and certain clinical subphenotypes, such as extra-pulmonary organ involvement, are discussed. Recent findings Associations of genetic variants in antigen-presenting molecules (HLA-DRB1) were shown to confer risk to sarcoidosis and certain disease phenotypes in populations of different ethnic origin. Specific DRB1 alleles, such as *0301 and *0302, appear to confer protection against chronic disease, but in an ethnic-specific manner illustrating the extensive genetic heterogeneity and complexity at this locus. Mechanistic studies of putative sarcoid antigens lend further credence to a role of HLA-DRB1 in disease pathogenesis. With relevance to granuloma formation, genes involved in apoptotic processes and immune cell activation were further confirmed (ANXA11 and BTNL2) in multiple ethnicities; others were newly identified (XAF1). Linking mechanism to clinical application, a TNF variant was shown to correlate with anti-TNF response in sarcoidosis patients. Summary The investigation of known and novel risk variants for sarcoidosis and specific clinical phenotypes in various ethnicities highlights the genetic complexity of the disease. Detailed subanalysis of disease phenotypes revealed the potential for prediction of extra-pulmonary organ involvement and therapy response based on the patient's genotype.

show abstract

Major histocompatibility complex class II andBTNL2associations in sarcoidosis

Cited by 24 publications

References 9 publications

Familial vs. sporadic sarcoidosis: BTNL2 polymorphisms, clinical presentations, and outcomes in a French cohort

Familial vs. sporadic sarcoidosis: BTNL2 polymorphisms, clinical presentations, and outcomes in a French cohort

The BTNL2 G16071A gene polymorphism increases granulomatous disease susceptibility

Granuloma genes in sarcoidosis

Contact Info

Product

Resources

About