Granuloma genes in sarcoidosis

Abstract

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.

Annexins family: insights into their functions and potential role in pathogenesis of sarcoidosis

“…More recent studies have confirmed that Annexin A11 and its regulation of apoptosis is a key genetic player in the development of sarcoidosis. The latest in sarcoidosis genetics research uses genome mapping to determine gene variants associated with increased granuloma formation [ 65 ]. A 2014 study of the Han Chinese population confirmed the potential role of ANXA11 SNPs in the genetic susceptibility to sarcoidosis.…”

“…In the era of personalized medicine, the annexin could be a novel focus. Annexin A11 thus may be a target for clinical trials in which a patient’s genetic risk factors are used to tailor treatment [ 65 ].…”

Cardiac sarcoidosis in monozygotic twins: An opportunity for early surveillance and treatment

“…Cardiac involvement is seen in 5% of presentations . Genetic factors, such as those that influence granulomatous processes, have been identified and play an important role in the development of sarcoidosis, but the cause is unknown . These genetic factors may determine disease pattern, severity, and prognosis.…”

The Effect of Genetics and Environmental Factors in Sarcoidosis Etiology

“…Bu bulgular, sarkoidozda gözlenen Th1 immün yanıtlarını ortaya çıkardığı bilinen HLA genotipleri ve hedeflenen antijenlere odaklanmış gen-çevre çalışmaları için zemin çalışmalarının oluşmasına imkân vermiştir. 15 GWAS ve aday gen araştırmalarında, BTNL2 (butyrophilin-like 2 gene), ANXA11 (Annexin 11), HLA bölgesindeki birkaç lokus ve IL-23/Th17 sinyal yolağı dâhil olmak üzere sarkoidoz için çeşitli genetik risk bölgeleri belirlenmiştir. Ayrıca, Blau sendromu, erken başlangıçlı sarkoidoz ve Chron hastalığı gibi granülomatöz hastalıklarda NOD2 mutasyonlarının da olduğu ifade edilmiştir.…”