{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T23:11:46Z","timestamp":1784675506676,"version":"3.55.0"},"reference-count":63,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"to Giorgia Girotto","award":["D70-RESRICGIROTTO"],"award-info":[{"award-number":["D70-RESRICGIROTTO"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Rheumatoid and psoriatic arthritis (RA and PsA) are inflammatory rheumatic disorders characterised by a multifactorial etiology. To date, the genetic contributions to the disease onset, severity and drug response are not clearly defined, and despite the development of novel targeted therapies, ~10% of patients still display poor treatment responses. We characterised a selected cohort of eleven non-responder patients aiming to define the genetic contribution to drug resistance. An accurate clinical examination of the patients was coupled with several high-throughput genetic testing, including HLA typing, SNPs-array and Whole Exome Sequencing (WES). The analyses revealed that all the subjects carry very rare HLA phenotypes which contain HLA alleles associated with RA development (e.g., HLA-DRB1*04, DRB1*10:01 and DRB1*01). Additionally, six patients also carry PsA risk alleles (e.g., HLA-B*27:02 and B*38:01). WES analysis and SNPs-array revealed 23 damaging variants with 18 novel \u201cdrug-resistance\u201d RA\/PsA candidate genes. Eight patients carry likely pathogenic variants within common genes (CYP21A2, DVL1, PRKDC, ORAI1, UGT2B17, MSR1). Furthermore, \u201cprivate\u201d damaging variants were identified within 12 additional genes (WNT10A, ABCB7, SERPING1, GNRHR, NCAPD3, CLCF1, HACE1, NCAPD2, ESR1, SAMHD1, CYP27A1, CCDC88C). This multistep approach highlighted novel RA\/PsA candidate genes and genotype-phenotype correlations potentially useful for clinicians in selecting the best therapeutic strategy.<\/jats:p>","DOI":"10.3390\/jpm12101618","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T01:43:11Z","timestamp":1665279791000},"page":"1618","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["High Throughput Genetic Characterisation of Caucasian Patients Affected by Multi-Drug Resistant Rheumatoid or Psoriatic Arthritis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5238-6422","authenticated-orcid":false,"given":"Paola","family":"Tesolin","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Eleonora","family":"Bertinetto","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, and Immunogenetic and Transplant Biology Service, University Hospital \u201cCitt\u00e0 della Salute e della Scienza\u201d, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Sonaglia","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine (DAME), ASUFC, University of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Cappellani","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health\u2014IRCCS, Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3598-2537","authenticated-orcid":false,"given":"Maria Pina","family":"Concas","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health\u2014IRCCS, Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6290-445X","authenticated-orcid":false,"given":"Anna","family":"Morgan","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health\u2014IRCCS, Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma Maria","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, and Immunogenetic and Transplant Biology Service, University Hospital \u201cCitt\u00e0 della Salute e della Scienza\u201d, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0573-464X","authenticated-orcid":false,"given":"Alen","family":"Zabotti","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine (DAME), ASUFC, University of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gasparini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy"},{"name":"Institute for Maternal and Child Health\u2014IRCCS, Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9437-9407","authenticated-orcid":false,"given":"Antonio","family":"Amoroso","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, and Immunogenetic and Transplant Biology Service, University Hospital \u201cCitt\u00e0 della Salute e della Scienza\u201d, 10124 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-6439","authenticated-orcid":false,"given":"Luca","family":"Quartuccio","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine (DAME), ASUFC, University of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-6589","authenticated-orcid":false,"given":"Giorgia","family":"Girotto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy"},{"name":"Institute for Maternal and Child Health\u2014IRCCS, Burlo Garofolo, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1093\/rheumatology\/keaa232","article-title":"The Genetics of Rheumatoid Arthritis","volume":"59","author":"Dedmon","year":"2020","journal-title":"Rheumatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.12688\/f1000research.19144.1","article-title":"Psoriatic Arthritis","volume":"8","author":"Ocampo","year":"2019","journal-title":"F1000Res"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00281-022-00912-0","article-title":"Genetics of Rheumatoid Arthritis","volume":"44","author":"Padyukov","year":"2022","journal-title":"Semin. Immunopathol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Laborde, C.M., Larzabal, L., Gonz\u00e1lez-Cantero, \u00c1., Castro-Santos, P., and D\u00edaz-Pe\u00f1a, R. (2022). Advances of Genomic Medicine in Psoriatic Arthritis. J. Pers. Med., 12.","DOI":"10.3390\/jpm12010035"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1016\/j.mayocp.2017.09.001","article-title":"Pharmacogenomics: Precision Medicine and Drug Response","volume":"92","author":"Weinshilboum","year":"2017","journal-title":"Mayo Clin. Proc."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wysocki, T., Olesi\u0144ska, M., and Paradowska-Gorycka, A. (2020). Current Understanding of an Emerging Role of HLA-DRB1 Gene in Rheumatoid Arthritis\u2014From Research to Clinical Practice. Cells, 9.","DOI":"10.3390\/cells9051127"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s11926-020-0886-x","article-title":"Complexities in Genetics of Psoriatic Arthritis","volume":"22","author":"Rahmati","year":"2020","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"775","DOI":"10.55563\/clinexprheumatol\/aiams5","article-title":"HLA-B*27 Is Significantly Enriched in Nordic Patients with Psoriatic Arthritis Mutilans","volume":"39","author":"Nikamo","year":"2021","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_9","unstructured":"Parameswaran, P., and Lucke, M. (2022). HLA B27 Syndromes, StatPearls."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S685","DOI":"10.1136\/annrheumdis-2019-216655","article-title":"EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: 2019 Update","volume":"79","author":"Smolen","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S700","DOI":"10.1136\/annrheumdis-2020-217159","article-title":"EULAR Recommendations for the Management of Psoriatic Arthritis with Pharmacological Therapies: 2019 Update","volume":"79","author":"Gossec","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s13075-021-02560-5","article-title":"Identification and Prediction of Difficult-to-Treat Rheumatoid Arthritis Patients in Structured and Unstructured Routine Care Data: Results from a Hackathon","volume":"23","author":"Messelink","year":"2021","journal-title":"Arthritis Res. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1136\/annrheumdis-2020-217344","article-title":"EULAR Definition of Difficult-to-Treat Rheumatoid Arthritis","volume":"80","author":"Nagy","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yamamoto, Y., Kanayama, N., Nakayama, Y., and Matsushima, N. (2022). Current Status, Issues and Future Prospects of Personalized Medicine for Each Disease. J. Pers. Med., 12.","DOI":"10.3390\/jpm12030444"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1097\/BOR.0000000000000298","article-title":"Rare Variants, Autoimmune Disease, and Arthritis","volume":"28","author":"Chung","year":"2016","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sonaglia, A., Comoretto, R., Pasut, E., Treppo, E., del Frate, G., Colatutto, D., Zabotti, A., de Vita, S., and Quartuccio, L. (2022). Safety of Biologic-DMARDs in Rheumatic Musculoskeletal Disorders: A Population-Based Study over the First Two Waves of COVID-19 Outbreak. Viruses, 14.","DOI":"10.3390\/v14071462"},{"key":"ref_17","first-page":"D948","article-title":"IPD-IMGT\/HLA Database","volume":"48","author":"Robinson","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.humimm.2012.01.005","article-title":"Estimation of Human Leukocyte Antigen Class I and Class II High-Resolution Allele and Haplotype Frequencies in the Italian Population and Comparison with Other European Populations","volume":"73","author":"Rendine","year":"2012","journal-title":"Hum. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_20","first-page":"7","article-title":"Predicting Functional Effect of Human Missense Mutations Using PolyPhen-2","volume":"76","author":"Adzhubei","year":"2013","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: Predicting Amino Acid Changes That Affect Protein Function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Limongelli, I., Marini, S., and Bellazzi, R. (2015). PaPI: Pseudo Amino Acid Composition to Score Human Protein-Coding Variants. BMC Bioinf., 16.","DOI":"10.1186\/s12859-015-0554-8"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/bioinformatics\/btu703","article-title":"DANN: A Deep Learning Approach for Annotating the Pathogenicity of Genetic Variants","volume":"31","author":"Quang","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/ejhg.2012.229","article-title":"Genetic Characterization of Northeastern Italian Population Isolates in the Context of Broader European Genetic Diversity","volume":"21","author":"Esko","year":"2013","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/ng.1076","article-title":"Five Amino Acids in Three HLA Proteins Explain Most of the Association between MHC and Seropositive Rheumatoid Arthritis","volume":"44","author":"Raychaudhuri","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_26","first-page":"e195","article-title":"Study of Human Leukocyte Antigen (HLA) in 13 Cases of Familial Frontal Fibrosing Alopecia: CYP21A2 Gene p.V281L Mutation from Congenital Adrenal Hyperplasia Linked to HLA Class I Haplotype HLA-A*33:01; B*14:02; C*08:02 as a Genetic Marker","volume":"60","year":"2019","journal-title":"Australas J. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.gene.2018.11.023","article-title":"Revisiting the Association of HLA Alleles and Haplotypes with CYP21A2 Mutations in a Large Cohort of Patients with Congenital Adrenal Hyperplasia","volume":"687","author":"Jayakrishnan","year":"2019","journal-title":"Gene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/gim.2014.178","article-title":"A High-Resolution Copy-Number Variation Resource for Clinical and Population Genetics","volume":"17","author":"Uddin","year":"2015","journal-title":"Genet. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.7150\/thno.36930","article-title":"Macrophage MSR1 Promotes BMSC Osteogenic Differentiation and M2-like Polarization by Activating PI3K\/AKT\/GSK3\u03b2\/\u03b2-Catenin Pathway","volume":"10","author":"Zhao","year":"2020","journal-title":"Theranostics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.4049\/jimmunol.1201680","article-title":"Macrophage Scavenger Receptor 1 (Msr1, SR-A) Influences B Cell Autoimmunity by Regulating Soluble Autoantigen Concentration","volume":"191","author":"Haasken","year":"2013","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cellsig.2018.03.004","article-title":"Dishevelled: A Masterful Conductor of Complex Wnt Signals","volume":"47","author":"Sharma","year":"2018","journal-title":"Cell Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.jaci.2015.01.040","article-title":"PRKDC Mutations Associated with Immunodeficiency, Granuloma, and Autoimmune Regulator-Dependent Autoimmunity","volume":"135","author":"Mathieu","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.coi.2018.03.021","article-title":"Ion Channelopathies of the Immune System","volume":"52","author":"Vaeth","year":"2018","journal-title":"Curr. Opin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.jaci.2017.10.031","article-title":"ORAI1 Mutations Abolishing Store-Operated Ca2+ Entry Cause Anhidrotic Ectodermal Dysplasia with Immunodeficiency","volume":"142","author":"Lian","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.jaci.2015.03.050","article-title":"A Novel Mutation in ORAI1 Presenting with Combined Immunodeficiency and Residual T-Cell Function","volume":"136","author":"Chou","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/clpt.2014.126","article-title":"Pharmacogenomics of Human Uridine Diphospho-Glucuronosyltransferases and Clinical Implications","volume":"96","author":"Guillemette","year":"2014","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6813","DOI":"10.3748\/wjg.v25.i47.6813","article-title":"Non-SMC Condensin I Complex Subunit D2 and Non-SMC Condensin II Complex Subunit D3 Induces Inflammation via the IKK\/NF-\u039aB Pathway in Ulcerative Colitis","volume":"25","author":"Yuan","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1002\/eji.201747360","article-title":"BATF Regulates the Expression of Nfil3, Wnt10a and MiR155hg for Efficient Induction of Antibody Class Switch Recombination in Mice","volume":"48","author":"Morman","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/ejhg.2013.300","article-title":"Variability in Dentofacial Phenotypes in Four Families with WNT10A Mutations","volume":"22","author":"Vink","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1038\/s41388-019-1118-6","article-title":"ABCB7 Simultaneously Regulates Apoptotic and Non-Apoptotic Cell Death by Modulating Mitochondrial ROS and HIF1\u03b1-Driven NF\u03baB Signaling","volume":"39","author":"Kim","year":"2020","journal-title":"Oncogene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/s41598-017-16667-w","article-title":"Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance: Functional and Structural Insight","volume":"8","author":"Caccia","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/humu.23917","article-title":"SERPING1 Mutation Update: Mutation Spectrum and C1 Inhibitor Phenotypes","volume":"41","author":"Ponard","year":"2020","journal-title":"Hum. Mutat."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Odle, A.K., Macnicol, M.C., Childs, G.V., and Macnicol, A.M. (2021). Post-Transcriptional Regulation of Gnrhr: A Checkpoint for Metabolic Control of Female Reproduction. Int J. Mol. Sci, 22.","DOI":"10.3390\/ijms22073312"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1056\/NEJM199711273372205","article-title":"A Family with Hypogonadotropic Hypogonadism and Mutations in the Gonadotropin-Releasing Hormone Receptor","volume":"337","author":"Young","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"155655","DOI":"10.1016\/j.cyto.2021.155655","article-title":"Influences of the IL-6 Cytokine Family on Bone Structure and Function","volume":"146","author":"Sims","year":"2021","journal-title":"Cytokine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.celrep.2016.04.032","article-title":"The Tumor Suppressor Hace1 Is a Critical Regulator of TNFR1-Mediated Cell Fate","volume":"15","author":"Tortola","year":"2016","journal-title":"Cell Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2217\/pgs.10.164","article-title":"The Effect of ESR1 and ESR2 Gene Polymorphisms on the Outcome of Rheumatoid Arthritis Treatment with Leflunomide","volume":"12","author":"Dziedziejko","year":"2011","journal-title":"Pharmacogenomics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e01970-20","DOI":"10.1128\/JVI.01970-20","article-title":"TRAF6 and TAK1 Contribute to SAMHD1-Mediated Negative Regulation of NF-\u039aB Signaling","volume":"95","author":"Espada","year":"2021","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Coggins, S.A., Mahboubi, B., Schinazi, R.F., and Kim, B. (2020). SAMHD1 Functions and Human Diseases. Viruses, 12.","DOI":"10.3390\/v12040382"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1111\/bjd.20400","article-title":"Familial Chilblain Lupus in a Child with Heterozygous Mutation in SAMHD1 and Normal Interferon Signature","volume":"185","author":"Linggonegoro","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"114621","DOI":"10.1016\/j.bcp.2021.114621","article-title":"Our Evolving Understanding of How 27-Hydroxycholesterol Influences Cancer","volume":"196","author":"Ma","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.18632\/oncotarget.22918","article-title":"Comprehensive Analysis of Gene Expression and DNA Methylation Datasets Identify Valuable Biomarkers for Rheumatoid Arthritis Progression","volume":"9","author":"Fang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3778","DOI":"10.1093\/rheumatology\/keaa860","article-title":"Difficult-to-Treat Rheumatoid Arthritis: Contributing Factors and Burden of Disease","volume":"60","author":"Roodenrijs","year":"2021","journal-title":"Rheumatology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"110171","DOI":"10.1016\/j.cellsig.2021.110171","article-title":"The Impact of Sex on Susceptibility to Systemic Lupus Erythematosus and Rheumatoid Arthritis; a Bioinformatics Point of View","volume":"88","author":"Ramezankhani","year":"2021","journal-title":"Cell Signal."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/s41435-020-0096-6","article-title":"Extra-Adrenal Glucocorticoid Biosynthesis: Implications for Autoimmune and Inflammatory Disorders","volume":"21","author":"Slominski","year":"2020","journal-title":"Genes Immun."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Cici, D., Corrado, A., Rotondo, C., and Cantatore, F.P. (2019). Wnt Signaling and Biological Therapy in Rheumatoid Arthritis and Spondyloarthritis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225552"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"108793","DOI":"10.1016\/j.clim.2021.108793","article-title":"Recent Advances on Signaling Pathways and Their Inhibitors in Rheumatoid Arthritis","volume":"230","author":"Liu","year":"2021","journal-title":"Clin. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1172\/JCI67349","article-title":"PRKDC Mutations in a SCID Patient with Profound Neurological Abnormalities","volume":"123","author":"Woodbine","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1002\/art.38805","article-title":"Methotrexate Inhibits NF-\u039aB Activity via Long Intergenic (Noncoding) RNA-P21 Induction","volume":"66","author":"Spurlock","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13223-020-00437-x","article-title":"Co-Occurrence between C1 Esterase Inhibitor Deficiency and Autoimmune Disease: A Systematic Literature Review","volume":"16","author":"Levy","year":"2020","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Nguyen, T.H.P., Hokstad, I., Fagerland, M.W., Mollnes, T.E., Hollan, I., Feinberg, M.W., Hjeltnes, G., Eilertsen, G., Mikkelsen, K., and Agewall, S. (2022). Antirheumatic Therapy Is Associated with Reduced Complement Activation in Rheumatoid Arthritis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0264628"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.3389\/fimmu.2018.01057","article-title":"Complement in the Initiation and Evolution of Rheumatoid Arthritis","volume":"9","author":"Holers","year":"2018","journal-title":"Front. Immunol"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0140-6736(21)02225-X","article-title":"Prophylactic Use of an Anti-Activated Factor XII Monoclonal Antibody, Garadacimab, for Patients with C1-Esterase Inhibitor-Deficient Hereditary Angioedema: A Randomised, Double-Blind, Placebo-Controlled, Phase 2 Trial","volume":"399","author":"Craig","year":"2022","journal-title":"Lancet"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/10\/1618\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:44:50Z","timestamp":1760143490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/10\/1618"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,30]]},"references-count":63,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["jpm12101618"],"URL":"https:\/\/doi.org\/10.3390\/jpm12101618","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,30]]}}}