Sarcoidosis in the Genomic Era: From Genetic Drivers to Tailored Therapies

Rivera NV, Ronninger M, Shchetynsky K, Franke A, Nothen MM, Muller-Quernheim J, et al. High-density genetic mapping identifies new susceptibility variants in sarcoidosis phenotypes and shows genomic-driven phenotypic differences. Am J Respir Crit Care Med. 2016;193(9):1008–22. https://doi.org/10.1164/rccm.201507-1372OC.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cao J, Li H, Yin X, Yang J, Pu L, Yang J. Global burden of pulmonary sarcoidosis from 1990 to 2021: a comprehensive analysis based on the GBD 2021 study. Front Med Lausanne. 2025. https://doi.org/10.3389/fmed.2025.1585005.

Article  PubMed  PubMed Central  Google Scholar 

Desai SR, Sivarasan N, Johannson KA, George PM, Culver DA, Devaraj A, et al. High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational delphi consensus study. Lancet Respir Med. 2024;12(5):409–18. https://doi.org/10.1016/s2213-2600(23)00267-9.

Article  PubMed  Google Scholar 

Harper LJ, Farver CF, Yadav R, Culver DA. A framework for exclusion of alternative diagnoses in sarcoidosis. J Autoimmun. 2024;149:103288. https://doi.org/10.1016/j.jaut.2024.103288.

Article  CAS  PubMed  Google Scholar 

Kırkıl G. Predictors of mortality in sarcoidosis. Clin Chest Med. 2024;45(1):175–83. https://doi.org/10.1016/j.ccm.2023.06.006.

Article  PubMed  Google Scholar 

Mayer-Fuentes A, Feijoo-Masso C, Flores-Chávez A, Policarpo-Torres G, Gómez de la Torre R, Vallejo-Grijalba J, et al. POS1127 Predictors of mortality in sarcoidosis: A nationwide cohort study from the SARCOGEAS registry. Ann Rheum Dis. 2025;84:1207–8. https://doi.org/10.1016/j.ard.2025.06.477.

Gerke AK. Morbidity and mortality in sarcoidosis. Curr Opin Pulm Med. 2014;20(5):472–8. https://doi.org/10.1097/mcp.0000000000000080.

Article  PubMed  PubMed Central  Google Scholar 

Tana C, Drent M, Nunes H, Kouranos V, Cinetto F, Jessurun NT, et al. Comorbidities of sarcoidosis. Ann Med. 2022;54(1):1014–35. https://doi.org/10.1080/07853890.2022.2063375.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cohen Aubart F, Lhote R, Amoura A, Valeyre D, Haroche J, Amoura Z, et al. Drug-induced sarcoidosis: an overview of the WHO pharmacovigilance database. J Intern Med. 2020;288(3):356–62. https://doi.org/10.1111/joim.12991.

Article  CAS  PubMed  Google Scholar 

Baughman RP, Grutters JC. New treatment strategies for pulmonary sarcoidosis: antimetabolites, biological drugs, and other treatment approaches. Lancet Respir Med. 2015;3(10):813–22. https://doi.org/10.1016/S2213-2600(15)00199-X.

Article  CAS  PubMed  Google Scholar 

Arango M-T, Perricone C, Kivity S, Cipriano E, Ceccarelli F, Valesini G, et al. HLA-DRB1 the notorious gene in the mosaic of autoimmunity. Immunol Res. 2017;65(1):82–98. https://doi.org/10.1007/s12026-016-8817-7.

Article  CAS  PubMed  Google Scholar 

Ferreiro-Iglesias A, Lesseur C, McKay J, Hung RJ, Han Y, Zong X, et al. Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity. Nat Commun. 2018;9(1):3927. https://doi.org/10.1038/s41467-018-05890-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Matzaraki V, Kumar V, Wijmenga C, Zhernakova A. The MHC locus and genetic susceptibility to autoimmune and infectious diseases. Genome Biol. 2017;18(1):76. https://doi.org/10.1186/s13059-017-1207-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sikorová K, Moon S-J, Yoon H-Y, Strnad A, Song JW, Petrek M. HLA class II variants defined by next generation sequencing are associated with sarcoidosis in Korean patients. Sci Rep. 2022;12(1):9302. https://doi.org/10.1038/s41598-022-13199-w.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sato H, Woodhead FA, Ahmad T, Grutters JC, Spagnolo P, van den Bosch JM, et al. Sarcoidosis HLA class II genotyping distinguishes differences of clinical phenotype across ethnic groups. Hum Mol Genet. 2010;19(20):4100–11. https://doi.org/10.1093/hmg/ddq325.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Strnad A, Sikorova K, Rapti A, Adam K, Charikiopoulou M, Kocourkova L, et al. Association of HLA variants and related SNPs with sarcoidosis and its phenotypes in the Greek patients. Gene. 2024;927:148706. https://doi.org/10.1016/j.gene.2024.148706.

Article  CAS  PubMed  Google Scholar 

Iannuzzi MC, Maliarik MJ, Poisson LM, Rybicki BA. Sarcoidosis susceptibility and resistance HLA-DQB1 alleles in African Americans. Am J Respir Crit Care Med. 2003;167(9):1225–31. https://doi.org/10.1164/rccm.200209-1097OC.

Article  PubMed  Google Scholar 

Badenhoop K, Walfish PG, Rau H, Fischer S, Nicolay A, Bogner U, et al. Susceptibility and resistance alleles of human leukocyte antigen (HLA) DQA1 and HLA DQB1 are shared in endocrine autoimmune disease. J Clin Endocrinol Metab. 1995;80(7):2112–7. https://doi.org/10.1210/jcem.80.7.7608264.

Article  CAS  PubMed  Google Scholar 

Miedema J, Cinetto F, Smed-Sörensen A, Spagnolo P. The immunopathogenesis of sarcoidosis. J Autoimmun. 2024;149:103247. https://doi.org/10.1016/j.jaut.2024.103247.

Article  CAS  PubMed  Google Scholar 

Hofmann S, Franke A, Fischer A, Jacobs G, Nothnagel M, Gaede KI, et al. Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis. Nat Genet. 2008;40(9):1103–6. https://doi.org/10.1038/ng.198.

Article  CAS  PubMed  Google Scholar 

Karakaya B, van der Vis JJ, Veltkamp M, Biesma DH, Grutters JC, van Moorsel CHM. ANXA11 rs1049550 Associates with Löfgren’s syndrome and chronic sarcoidosis patients. Cells. 2022;11(9):20220505. https://doi.org/10.3390/cells11091557.

Article  CAS  Google Scholar 

Levin AM, Iannuzzi MC, Montgomery CG, Trudeau S, Datta I, McKeigue P, et al. Association of ANXA11 genetic variation with sarcoidosis in African Americans and European Americans. Genes Immun. 2013;14(1):13–8. https://doi.org/10.1038/gene.2012.48.

Article  CAS  PubMed  Google Scholar 

Xianjun F, Shuzhi Z, Yanrong Y, Shasha Z, Yunxia L, Xinyuan G, et al. Annexin A11 (ANXA11) gene polymorphisms are associated with sarcoidosis in a Han Chinese population: a case–control study. BMJ Open. 2014;4(7):e004466. https://doi.org/10.1136/bmjopen-2013-004466.

Article  Google Scholar 

Kullberg S, Darlington P, Ellinghaus D, Prasse A, Iseda T, Chuquimia O, et al. Unraveling genetic mysteries: phenotype-shaping profiles in chronic sarcoidosis. medRxiv. 2024:2024.12.29.24319750. https://doi.org/10.1101/2024.12.29.24319750.

Kallberg H, Padyukov L, Plenge RM, Ronnelid J, Gregersen PK, van der Helm-van Mil AH, et al. Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet. 2007;80(5):867–75. https://doi.org/10.1086/516736.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wilkinson B, Downey JS, Rudd CE. T-cell signalling and immune system disorders. Expert Rev Mol Med. 2005;7(29):1–29. https://doi.org/10.1017/s1462399405010264.

Article  PubMed  Google Scholar 

Chatterjee D, Parkash J, Sharma A. A bioinformatics approach to solving the puzzle of autoimmune diseases. Int J Bioinform Res Appl. 2022;18(5):415–59. https://doi.org/10.1504/ijbra.2022.128245.

Article  Google Scholar 

Rivera NV, Hagemann-Jensen M, Ferreira MAR, Kullberg S, Eklund A, Martin NG, et al. Common variants of T-cells contribute differently to phenotypic variation in sarcoidosis. Sci Rep. 2017;7(1):5623. https://doi.org/10.1038/s41598-017-05754-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fischer A, Nothnagel M, Franke A, Jacobs G, Saadati HR, Gaede KI, et al. Association of inflammatory bowel disease risk loci with sarcoidosis, and its acute and chronic subphenotypes. Eur Respir J. 2011;37(3):610–6. https://doi.org/10.1183/09031936.00049410.

Article  CAS  PubMed 

Comments (0)

No login
gif