{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T02:54:47Z","timestamp":1781924087677,"version":"3.54.5"},"reference-count":36,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T00:00:00Z","timestamp":1574294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polpharma Scientific Fundation","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Mixed connective tissue disease (MCTD) is a rare complex autoimmune disease in which autoantigens are recognized by endosomal TLRs. Their activation induces a higher secretion of the type I interferons, IFN-\u03b3 and the up-regulation of the INF-inducible genes. The present study aimed to investigate whether SNPs that are located in the IFN-A, IFN-B, and IFN-G genes are associated with MCTD. 145 MCTD patients and 281 healthy subjects were examined for IFN-A, IFN-B, and IFN-G genetic variants by TaqMan SNP genotyping assay. ELISA determined IFN-\u03b1\/-\u03b2\/-\u03b3 serum levels. Among the seven tested SNPs, four polymorphisms: IFN-A rs10757212, IFN-A rs3758236, IFN-G rs2069705, IFN-G rs2069718, as well as INF-G rs1861493A\/rs2069705A\/rs2069718G haplotype were significantly associated with a predisposition for MCTD. Raynaud\u2019s phenomenon, erosive arthritis, swollen hands and fingers, and sclerodactyly were significantly more frequently observed in MCTD patients with IFN-G rs2069718 G allele than in patients with IFN-G rs2069718 A allele. We also found that anti-U1-A autoantibodies most frequently occurred in MCTD patients with rs2069718 GA genotype, while the IFN-G rs2069705 AG and rs2069718 GA genotypes might be a marker of anti-Ro60 presence in MCTD patients. Our results indicate that IFN-G genetic variants may be potential genetic biomarkers for MCTD susceptibility and severity.<\/jats:p>","DOI":"10.3390\/jcm8122046","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T02:49:27Z","timestamp":1574390967000},"page":"2046","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Interferons (IFN-A\/-B\/-G) Genetic Variants in Patients with Mixed Connective Tissue Disease (MCTD)"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4249-3136","authenticated-orcid":false,"given":"Agnieszka","family":"Paradowska-Gorycka","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6384-2916","authenticated-orcid":false,"given":"Anna","family":"Wajda","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Stypinska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Walczuk","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1255-1830","authenticated-orcid":false,"given":"Marcela","family":"Walczyk","sequence":"additional","affiliation":[{"name":"Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Felis-Giemza","sequence":"additional","affiliation":[{"name":"Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Poluch-Lewandowska","sequence":"additional","affiliation":[{"name":"Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"Olesi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw 02-637, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/0002-9343(72)90064-2","article-title":"Mixed connective tissue disease\u2014An apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA)","volume":"52","author":"Sharp","year":"1972","journal-title":"Am. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1001\/archderm.1976.01630350011003","article-title":"Mixed connective tissue disease","volume":"112","author":"Minkin","year":"1976","journal-title":"Arch. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.berh.2012.01.009","article-title":"Mixed connective tissue disease: An overview of clinical manifestations, diagnosis and treatment","volume":"26","author":"Shoenfeld","year":"2012","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.rdc.2005.04.007","article-title":"Does mixed connective tissue disease exist? Yes","volume":"31","author":"Aringer","year":"2005","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.rdc.2005.04.004","article-title":"Autoantibodies in the pathogenesis of mixed connective tissue disease","volume":"31","author":"Greidinger","year":"2005","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Tani, C., Carli, L., Vagnani, S., Talarico, R., Baldini, C., Mosca, M., and Bombardieri, S. (2014). The diagnosis and classification of mixed connective tissue disease. J. Autoimmun., 46\u201349.","DOI":"10.1016\/j.jaut.2014.01.008"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/j.0105-2896.2009.00863.x","article-title":"The U1-snRNP complex: Structural properties relating to autoimmune pathogenesis in rheumatic diseases","volume":"233","author":"Kattah","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"30757","DOI":"10.1016\/S0021-9258(18)47343-7","article-title":"Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death","volume":"269","author":"Miller","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"94","DOI":"10.5114\/reum.2015.51509","article-title":"U1-RNP and TLR receptors in the pathogenesis of mixed connective tissue disease. Part I. The U1-RNP complex and its biological significance in the pathogenesis of mixed connective tissue disease","volume":"53","year":"2015","journal-title":"Reumatologia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.autrev.2006.08.007","article-title":"Anti-RNP immunity: Implications for tissue injury and the pathogenesis of connective tissue disease","volume":"6","author":"Keith","year":"2007","journal-title":"Autoimmun. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.autrev.2005.02.003","article-title":"Apoptotic modifications affect the autoreactivity of the U1 snRNP autoantigen","volume":"4","author":"Hof","year":"2005","journal-title":"Autoimmun. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.clim.2008.03.461","article-title":"Immune pathogenesis of Mixed Connective Tissue Disease: A short analytical review","volume":"128","author":"Hoffman","year":"2008","journal-title":"Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.pharmthera.2013.03.003","article-title":"Toll-like receptors as therapeutic targets for autoimmune connective tissue diseases","volume":"138","author":"Li","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_14","first-page":"S21","article-title":"The importance of the type I interferon system in autoimmunity","volume":"34","author":"Ronnblom","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.berh.2017.10.003","article-title":"Role of interferons in SLE","volume":"31","author":"Bengtsson","year":"2017","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_16","first-page":"1662","article-title":"Type I interferon-mediated autoimmune diseases: Pathogenesis, diagnosis and targeted therapy","volume":"56","author":"Psarras","year":"2017","journal-title":"Rheumatology (Oxford)"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s13075-018-1683-z","article-title":"Interferon-\u03bb3\/4 genetic variants and interferon-\u03bb3 serum levels are biomarkers of lupus nephritis and disease activity in Taiwanese","volume":"20","author":"Chen","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nri3787","article-title":"Type I interferons in infectious disease","volume":"15","author":"McNab","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1002\/art.37821","article-title":"Disease mechanisms in rheumatology\u2013tools and pathways: Plasmacytoid dendritic cells and their role in autoimmune rheumatic diseases","volume":"65","author":"Eloranta","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/ar3803","article-title":"Antagonist-mediated down-regulation of Toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus","volume":"14","author":"Yu","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1007\/s10875-013-9887-0","article-title":"Distinct autoantibody profiles in systemic lupus erythematosus patients are selectively associated with TLR7 and TLR9 upregulation","volume":"33","author":"Chauhan","year":"2013","journal-title":"J. Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1093\/rheumatology\/ker400","article-title":"Expression of Toll-like receptors and their detection of nuclear self-antigen leading to immune activation in JSLE","volume":"51","author":"Midgley","year":"2012","journal-title":"Rheumatology (Oxford)"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5793","DOI":"10.1038\/s41598-018-24198-1","article-title":"A novel two-score system for interferon status segregates autoimmune diseases and correlates with clinical features","volume":"8","author":"Psarras","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1002\/art.30356","article-title":"Genetic analyses of interferon pathway-related genes reveal multiple new loci associated with systemic lupus erythematosus","volume":"63","author":"Ramos","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/gene.2014.57","article-title":"Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus","volume":"16","author":"Kariuki","year":"2015","journal-title":"Genes Immun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1089\/jir.2011.0071","article-title":"Interferon alpha as a primary pathogenic factor in human lupus","volume":"31","author":"Niewold","year":"2011","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1002\/art.40304","article-title":"Lupus-Associated Functional Polymorphism in PNP Causes Cell Cycle Abnormalities and Interferon Pathway Activation in Human Immune Cells","volume":"69","author":"Dorschner","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ghodke-Puranik, Y., Imgruet, M., Dorschner, J.M., Shrestha, P., McCoy, K., Kelly, J.A., Marion, M., Guthridge, J.M., Langefeld, C.D., and Harley, J.B. (2019). Novel genetic associations with interferon in systemic lupus erythematosus identified by replication and fine-mapping of trait-stratified genome-wide screen. Cytokine.","DOI":"10.1016\/j.cyto.2018.12.014"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/ng.3603","article-title":"Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus","volume":"48","author":"Morris","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jaut.2016.08.001","article-title":"The genetic basis of systemic lupus erythematosus: What are the risk factors and what have we learned","volume":"74","author":"Teruel","year":"2016","journal-title":"J. Autoimmun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1093\/rheumatology\/ker263","article-title":"Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signaling and strengthens the role of IRF5 in disease susceptibility in a Northern European population","volume":"51","author":"Hellquist","year":"2012","journal-title":"Rheumatology (Oxford)"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Skaug, B., and Assassi, S. (2019). Type I interferon dysregulation in Systemic Sclerosis. Cytokine.","DOI":"10.1016\/j.cyto.2018.12.018"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.3389\/fimmu.2019.01880","article-title":"Epigenome-Wide Comparative Study Reveals Key Differences Between Mixed Connective Tissue Disease and Related Systemic Autoimmune Diseases","volume":"10","author":"Barturen","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.clim.2018.03.014","article-title":"Epigenome-wide association studies for systemic autoimmune diseases: The road behind and the road ahead","volume":"196","year":"2018","journal-title":"Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/s11926-017-0657-5","article-title":"Epigenetic variability in systemic lupus erythematosus: What we learned from genome-wide DNA methylation studies","volume":"19","author":"Teruel","year":"2017","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"R302","DOI":"10.1186\/ar1490","article-title":"Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue disease","volume":"7","author":"Hof","year":"2005","journal-title":"Arthritis Res. Ther."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/12\/2046\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:36:30Z","timestamp":1760189790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/12\/2046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,21]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["jcm8122046"],"URL":"https:\/\/doi.org\/10.3390\/jcm8122046","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,21]]}}}