Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects

Direskeneli, Haner; emmungil, hakan; İlgen, Ufuk

doi:10.3906/sag-2011-235

Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects

Hakan EMMUNGİL, (Trakya Üniversitesi, Tıp Fakültesi, Romatoloji Anabilim Dalı, Edirne, Türkiye)

Ufuk İLGEN, (Trakya Üniversitesi, Tıp Fakültesi, Romatoloji Anabilim Dalı, Edirne, Türkiye)

Haner DİRESKENELİ (Marmara Üniversitesi, Tıp Fakültesi, Romatoloji Anabilim Dalı, İstanbul, Türkiye)

Turkish Journal of Medical Sciences

2 0

Yıl: 2021 Cilt: 51 Sayı: 4 Sayfa Aralığı: 1601 - 1614 Metin Dili: İngilizce DOI: 10.3906/sag-2011-235 İndeks Tarihi: 10-01-2022

Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects

Öz:

Abstract: Psoriatic arthritis (PsA) is an underdiagnosed entity with a broad impact on the quality of life. Although the pathogenesis is largely unknown, autoimmune footprints of the inflammation in PsA have increasingly been recognized. Most of the genetic variation predisposing to PsA is mapped to the class I major histocompatibility complex (MHC) region and shared by a variety of autoimmune diseases. Polymorphisms in the genes IL12B, IL23R, IL13, TNIP1, TRAF3IP2, TYK2, and many others explain the nonHLA genetic risk with little known functional consequences. Entheseal and synovial cellular infiltrate with oligoclonal CD8+ T cells and occasional germinal centers, loss of regulatory T cell function, and specific autoantibodies such as anti-PsA peptide, anti-LL-37, and anti-ADAMTSL5 are the immunopathological findings suggestive of autoimmunity. These were supported by clinical observations of autoimmune multimorbidity and treatment response to calcineurin/mTOR and co-stimulation inhibition.Key words: Autoantibody, autoimmunity, genetic, psoriasis, psoriatic arthritis

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1. Prey S, Paul C, Bronsard V, Puzenat E, Gourraud PA et al. Assessment of risk of psoriatic arthritis in patients with plaque psoriasis: a systematic review of the literature. Journal of the European Academy of Dermatology and Venereology 2010; 24 (Suppl 2): 31-35. doi: 10.1111/j.1468-3083.2009.03565.x
2. Alenius GM, Stenberg B, Stenlund H, Lundblad M, Dahlqvist SR. Inflammatory joint manifestations are prevalent in psoriasis: prevalence study of joint and axial involvement in psoriatic patients, and evaluation of a psoriatic and arthritic questionnaire. The Journal of Rheumatology 2002; 29 (12): 2577-2582.
3. Reich K, Krüger K, Mössner R, Augustin M. Epidemiology and clinical pattern of psoriatic arthritis in Germany: a prospective interdisciplinary epidemiological study of 1511 patients with plaque-type psoriasis. British Journal of Dermatology 2009; 160 (5): 1040-1047. doi: 10.1111/j.1365-2133.2008.09023.x
4. Mease PJ, Menter MA. Quality-of-life issues in psoriasis and psoriatic arthritis: outcome measures and therapies from a dermatological perspective. Journal of the American Academy of Dermatology 2006; 54 (4): 685-704. doi: 10.1016/j. jaad.2005.10.008
5. Gudu T, Gossec L. Quality of life in psoriatic arthritis. Expert Review of Clinical Immunology 2018; 14 (5): 405-417. doi: 10.1080/1744666X.2018.1468252
6. Rosen CF, Mussani F, Chandran V, Eder L, Thavaneswaran A et al. Patients with psoriatic arthritis have worse quality of life than those with psoriasis alone. Rheumatology (Oxford) 2012; 51 (3): 571-576. doi: 10.1093/rheumatology/ker365
7. Scarpa R, Ayala F, Caporaso N, Olivieri I. Psoriasis, psoriatic arthritis, or psoriatic disease? The Journal of Rheumatology 2006; 33 (2): 210-212.
8. Puig L, Julià A, Marsal S. The pathogenesis and genetics of psoriasis. Actas Dermo-Sifiliográficas 2014; 105 (6): 535-545. doi: 10.1016/j.ad.2012.11.006
9. O’Rielly DD, Rahman P. Genetics of susceptibility and treatment response in psoriatic arthritis. Nature Reviews Rheumatology 2011; 7 (12): 718-732. doi: 10.1038/nrrheum.2011.169
10. Chandran V, Rahman P. Update on the genetics of spondyloarthritis--ankylosing spondylitis and psoriatic arthritis. Best Practice & Research: Clinical Rheumatology 2010; 24 (5): 579-588. doi: 10.1016/j.berh.2010.05.006
11. Smith RL, Warren RB, Griffiths CE, Worthington J. Genetic susceptibility to psoriasis: an emerging picture. Genome Medicine 2009; 1 (7): 72. doi: 10.1186/gm72
12. Ayala-Fontánez N, Soler DC, McCormick TS. Current knowledge on psoriasis and autoimmune diseases. Psoriasis (Auckland) 2016; 6: 7-32. doi: 10.2147/PTT.S64950
13. Stuart PE, Nair RP, Tsoi LC, Tejasvi T, Das S et al. Genomewide association analysis of psoriatic arthritis and cutaneous psoriasis reveals differences in their genetic architecture. American Journal of Human Genetics 2015; 97 (6): 816-836. doi: 10.1016/j.ajhg.2015.10.019
14. Ellinghaus E, Stuart PE, Ellinghaus D, Nair RP, Debrus S et al. Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL. Journal of Investigative Dermatology 2012; 132 (4): 1133-1140. doi: 10.1038/jid.2011.415
15. Tsoi LC, Spain SL, Ellinghaus E, Stuart PE, Capon F et al. Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. Nature Communications 2015; 6: 7001. doi: 10.1038/ncomms8001
16. Yin X, Low HQ, Wang L, Li Y, Ellinghaus E et al. Genomewide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility. Nature Communications 2015; 6: 6916. doi: 10.1038/ncomms7916
17. Tsoi LC, Stuart PE, Tian C, Gudjonsson JE, Das S et al. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants. Nature Communications 2017; 8: 15382. doi: 10.1038/ncomms15382
18. Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? British Journal of Dermatology 2020; 182 (4): 840-848. doi: 10.1111/bjd.18245
19. Chimenti MS, Caso F, Alivernini S, De Martino E, Costa L et al. Amplifying the concept of psoriatic arthritis: the role of autoimmunity in systemic psoriatic disease. Autoimmunity Reviews 2019; 18 (6): 565-575. doi: 10.1016/j.autrev.2018.11.007
20. Rahman P, Inman RD, El-Gabalawy H, Krause DO. Pathophysiology and pathogenesis of immune-mediated inflammatory diseases: commonalities and differences. The Journal of Rheumatology Supplement 2010; 85: 11-26. doi: 10.3899/jrheum.091462
21. Ambarus C, Yeremenko N, Tak PP, Baeten D. Pathogenesis of spondyloarthritis: autoimmune or autoinflammatory? Current Opinion in Rheumatology 2012; 24 (4): 351-358. doi: 10.1097/ BOR.0b013e3283534df4
22. Chandran V, Schentag CT, Brockbank JE, Pellett FJ, Shanmugarajah S et al. Familial aggregation of psoriatic arthritis. Annals of the Rheumatic Diseases 2009; 68 (5): 664- 667. doi: 10.1136/ard.2008.089367
23. Moll JM, Wright V. Familial occurrence of psoriatic arthritis. Annals of the Rheumatic Diseases 1973; 32 (3): 181-201. doi: 10.1136/ard.32.3.181
24. Lang KS, Burow A, Kurrer M, Lang PA, Recher M. The role of the innate immune response in autoimmune disease. Journal of Autoimmunity 2007; 29 (4): 206-212. doi: 10.1016/j. jaut.2007.07.018
25. Alperin JM, Ortiz-Fernández L, Sawalha AH. Monogenic lupus: a developing paradigm of disease. Frontiers in Immunology 2018; 9: 2496. doi: 10.3389/fimmu.2018.02496
26. Chandran V, Bull SB, Pellett FJ, Ayearst R, Rahman P et al. Human leukocyte antigen alleles and susceptibility to psoriatic arthritis. Human Immunology 2013; 74 (10): 1333-1338. doi: 10.1016/j.humimm.2013.07.014
27. Ogawa K, Okada Y. The current landscape of psoriasis genetics in 2020. Journal of Dermatological Science 2020; 99 (1): 2-8. doi: 10.1016/j.jdermsci.2020.05.008
28. Shi C, Rattray M, Barton A, Bowes J, Orozco G. Using functional genomics to advance the understanding of psoriatic arthritis. Rheumatology (Oxford) 2020; 59 (11): 3137-3146. doi: 10.1093/rheumatology/keaa283
29. Rahman P, Elder JT. Genetic epidemiology of psoriasis and psoriatic arthritis. Annals of the Rheumatic Diseases 2005; 64 Suppl 2 (Suppl 2): ii37-ii39. doi: 10.1136/ard.2004.030775
30. Nair RP, Stuart PE, Nistor I, Hiremagalore R, Chia NVC et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. American Journal of Human Genetics 2006; 78 (5): 827-851. doi: 10.1086/503821
31. Jenisch S, Henseler T, Nair RP, Guo SW, Westphal E et al. Linkage analysis of human leukocyte antigen (HLA) markers in familial psoriasis: strong disequilibrium effects provide evidence for a major determinant in the HLA-B/-C region. American Journal of Human Genetics 1998; 63 (1): 191-199. doi: 10.1086/301899
32. Kantor SM, Hsu SH, Bias WB, Arnett FC. Clinical and immunogenetic subsets of psoriatic arthritis. Clinical and Experimental Rheumatology 1984; 2 (2): 105-109.
33. Duffin KC, Chandran V, Gladman DD, Krueger GG, Elder JT et al. Genetics of psoriasis and psoriatic arthritis: update and future direction. The Journal of Rheumatology 2008; 35 (7): 1449-1453.
34. Gladman DD, Farewell VT. The role of HLA antigens as indicators of disease progression in psoriatic arthritis. Multivariate relative risk model. Arthritis & Rheumatism 1995; 38 (6): 845-850. doi: 10.1002/art.1780380619
35. Korendowych E, Dixey J, Cox B, Jones S, McHugh N. The Influence of the HLA-DRB1 rheumatoid arthritis shared epitope on the clinical characteristics and radiological outcome of psoriatic arthritis. The Journal Rheumatology 2003; 30 (1): 96-101.
36. Arakawa A, Siewert K, Stöhr J, Besgen P, Kim SM et al. Melanocyte antigen triggers autoimmunity in human psoriasis. Journal of Experimental Medicine 2015; 212 (13): 2203-2212. doi: 10.1084/jem.20151093
37. Di Marco M, Schuster H, Backert L, Ghosh M, Rammensee HG et al. Unveiling the peptide motifs of HLA-C and HLA-G from naturally presented peptides and generation of binding prediction matrices. Journal of Immunology 2017; 199 (8): 2639-2651. doi: 10.4049/jimmunol.1700938
38. FitzGerald O, Haroon M, Giles JT, Winchester R. Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. Arthritis Research and Therapy 2015; 17 (1) :115. doi: 10.1186/s13075-015-0640-3
39. Arosa FA, Santos SG, Powis SJ. Open conformers: the hidden face of MHC-I molecules. Trends in Immunology 2007; 28 (3): 115-123. doi: 10.1016/j.it.2007.01.002
40. Siegel RJ, Bridges SL Jr, Ahmed S. HLA-C: an accomplice in rheumatic diseases. ACR Open Rheumatology 2019; 1 (9): 571-579. doi: 10.1002/acr2.11065
41. Kollnberger S, Bird L, Sun MY, Retiere C, Braud VM et al. Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthritis & Rheumatism 2002; 46 (11): 2972-2982. doi: 10.1002/art.10605
42. Payeli SK, Kollnberger S, Marroquin Belaunzaran O, Thiel M, McHugh K et al. Inhibiting HLA-B27 homodimer-driven immune cell inflammation in spondylarthritis. Arthritis & Rheumatism 2012; 64 (10): 3139-3149. doi: 10.1002/art.34538
43. Enciso-Vargas M, Alvarado-Ruíz L, Suárez-Villanueva AS, Macías-Barragán J, Montoya-Buelna M et al. Association study between psoriatic arthritis and killer immunoglobulin-like receptor (KIR) genes: a meta-analysis. Immunological Investigations 2021; 50 (2-3): 152-163. doi: 10.1080/08820139.2020.1713145
44. Noble JA, Valdes AM. Genetics of the HLA region in the prediction of type 1 diabetes. Current Diabetes Reports 2011; 11 (6): 533-542. doi: 10.1007/s11892-011-0223-x
45. Bech K, Lumholtz B, Nerup J, Thomsen M, Platz P et al. HLA antigens in Graves’ disease. Acta Endocrinologica (Copenhagen) 1977; 86 (3): 510-516. doi: 10.1530/ acta.0.0860510
46. Simmonds MJ, Gough SC. Unravelling the genetic complexity of autoimmune thyroid disease: HLA, CTLA-4 and beyond. Clinical and Experimental Immunology 2004; 136 (1): 1-10. doi: 10.1111/j.1365-2249.2004.02424.x
47. Saruhan-Direskeneli G, Hughes T, Yilmaz V, Durmus H, Adler A et al. Genetic heterogeneity within the HLA region in three distinct clinical subgroups of myasthenia gravis. Clinical Immunology 2016; 166-167: 81-88. doi: 10.1016/j. clim.2016.05.003
48. Yeo TW, De Jager PL, Gregory SG, Barcellos LF, Walton A et al. A second major histocompatibility complex susceptibility locus for multiple sclerosis. Annals of Neurology 2007; 61 (3): 228-236. doi: 10.1002/ana.21063
49. Sciurti M, Fornaroli F, Gaiani F, Bonaguri C, Leandro G et al. Genetic susceptibilty and celiac disease: what role do HLA haplotypes play? Acta Biomedica 2018; 89 (9-S): 17-21. doi: 10.23750/abm.v89i9-S.7953
50. Newton JL, Harney SM, Wordsworth BP, Brown MA. A review of the MHC genetics of rheumatoid arthritis. Genes & Immunity 2004; 5 (3): 151-157. doi: 10.1038/sj.gene.6364045
51. Morris DL, Taylor KE, Fernando MM, Nititham J, AlarcónRiquelme ME et al. Unraveling multiple MHC gene associations with systemic lupus erythematosus: model choice indicates a role for HLA alleles and non-HLA genes in Europeans. American Journal of Human Genetics 2012; 91 (5): 778-793. doi: 10.1016/j.ajhg.2012.08.026
52. Gershwin ME, Terasaki I, Graw R, Chused TM. Increased frequency of HL-A8 in Sjogren’s syndrome. Tissue Antigens 1975; 6 (5): 342-346. doi: 10.1111/j.1399-0039.1975.tb00653.x
53. Hernández-Molina G, Vargas-Alarcón G, Rodríguez-Pérez JM, Martínez-Rodríguez N, Lima G et al. High-resolution HLA analysis of primary and secondary Sjögren’s syndrome: a common immunogenetic background in Mexican patients. Rheumatology International 2015; 35 (4): 643-649. doi: 10.1007/s00296-014-3143-7
54. García Portales R, Belmonte Lope MA, Camps García MT, Ocón Sánchez P, Alonso Ortiz A et al. Immunogenetics of the Sjogren’s syndrome in southern Spain. Anales de Medicina Interna 1994; 11 (2): 56-61. (in Spanish)
55. Karp DR, Marthandan N, Marsh SG, Ahn C, Arnett FC et al. Novel sequence feature variant type analysis of the HLA genetic association in systemic sclerosis. Human Molecular Genetics 2010; 19 (4): 707-719. doi: 10.1093/hmg/ddp521
56. Brochado MJ, Nascimento DF, Campos W, Deghaide NH, Donadi EA et al. Differential HLA class I and class II associations in pemphigus foliaceus and pemphigus vulgaris patients from a prevalent Southeastern Brazilian region. Journal of Autoimmunity 2016; 72: 19-24. doi: 10.1016/j. jaut.2016.04.007
57. Gil JM, Weber R, Rosales CB, Rodrigues H, Sennes LU et al. Study of the association between human leukocyte antigens (HLA) and pemphigus vulgaris in Brazilian patients. International Journal of Dermatology 2017; 56 (5): 557-562. doi: 10.1111/ijd.13577
58. Zhang J, Wang G. Genetic predisposition to bullous pemphigoid. Journal of Dermatological Science 2020; 100 (2): 86-91. doi: 10.1016/j.jdermsci.2020.05.010
59. Zhang XJ, Liu HS, Liang YH, Sun LD, Wang JY et al. Association of HLA class I alleles with vitiligo in Chinese Hans. Journal of Dermatological Science 2004; 35 (2): 165-168. doi: 10.1016/j. jdermsci.2004.05.003
60. Shen C, Gao J, Sheng Y, Dou J, Zhou F et al. Genetic susceptibility to vitiligo: GWAS approaches for identifying vitiligo susceptibility genes and loci. Frontiers in Genetics 2016; 7: 3. doi: 10.3389/fgene.2016.00003
61. Lammert C, McKinnon EJ, Chalasani N, Phillips EJ. Novel HLA class I alleles outside the extended DR3 haplotype are protective against autoimmune hepatitis. Clinical and Translational Gastroenterology 2019; 10 (6): e00032. doi: 10.14309/ctg.0000000000000032
62. Invernizzi P. Human leukocyte antigen in primary biliary cirrhosis: an old story now reviving. Hepatology 2011; 54 (2): 714-723. doi: 10.1002/hep.24414
63. Donaldson PT, Norris S. Immunogenetics in PSC. Best Practice & Research: Clininical Gastroenterology 2001; 15 (4): 611-627. doi: 10.1053/bega.2001.0208
64. O’Hanlon TP, Carrick DM, Arnett FC, Reveille JD, Carrington M et al. Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies: distinct HLA-A, -B, -Cw, -DRB1 and -DQA1 allelic profiles and motifs define clinicopathologic groups in caucasians. Medicine (Baltimore) 2005; 84 (6): 338-349. doi: 10.1097/01.md.0000189818.63141.8c
65. Candore G, Lio D, Colonna Romano G, Caruso C. Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: effect of multiple gene interactions. Autoimmunity Reviews 2002; 1 (1-2): 29-35. doi: 10.1016/s1568-9972(01)00004-0
66. Kiszel P, Kovács M, Szalai C, Yang Y, Pozsonyi E et al. Frequency of carriers of 8.1 ancestral haplotype and its fragments in two Caucasian populations. Immunological Investigations 2007; 36 (3): 307-319. doi: 10.1080/08820130701241404
67. Gonzalez S, Martinez-Borra J, Torre-Alonso JC, GonzalezRoces S, Sanchez del Río J et al. The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to the development of psoriatic arthritis and is independent of the association of Cw*0602 in psoriasis. Arthritis & Rheumatism 1999; 42 (5): 1010- 1016. doi: 10.1002/1529-0131(199905)42:5<1010::AIDANR21>3.0.CO;2-H
68. González S, Martínez-Borra J, López-Vázquez A, GarcíaFernández S, Torre-Alonso JC et al. MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis. The Journal of Rheumatology 2002; 29 (5): 973-978.
69. Rahman P, Siannis F, Butt C, Farewell V, Peddle L et al. TNFalpha polymorphisms and risk of psoriatic arthritis. Annals of the Rheumatic Diseases 2006; 65 (7): 919-923. doi: 10.1136/ard.2005.039164
70. Murdaca G, Gulli R, Spanò F, Lantieri F, Burlando M et al. TNF-α gene polymorphisms: association with disease susceptibility and response to anti-TNF-α treatment in psoriatic arthritis. Journal of Investigative Dermatology 2014; 134 (10): 2503-2509. doi: 10.1038/jid.2014.123
71. Zuo J, Mohammed F, Moss P. The biological influence and clinical relevance of polymorphism within the NKG2D ligands. Frontiers in Immunology 2018; 9: 1820. doi: 10.3389/ fimmu.2018.01820
72. Wensveen FM, Jelenčić V, Polić B. NKG2D: a master regulator of immune cell responsiveness. Frontiers in Immunology 2018; 9: 441. doi: 10.3389/fimmu.2018.00441
73. Van Belle TL, Von Herrath MG. The role of the activating receptor NKG2D in autoimmunity. Molecular Immunology 2009; 47 (1): 8-11. doi: 10.1016/j.molimm.2009.02.023
74. Mekinian A, Tamouza R, Pavy S, Gestermann N, Ittah M et al. Functional study of TNF-α promoter polymorphisms: literature review and meta-analysis. European Cytokine Network 2011; 22 (2): 88-102. doi: 10.1684/ecn.2011.0285
75. Höhler T, Grossmann S, Stradmann-Bellinghausen B, Kaluza W, Reuss E et al. Differential association of polymorphisms in the TNFalpha region with psoriatic arthritis but not psoriasis. Annals of the Rheumatic Diseases 2002; 61 (3): 213-218. doi: 10.1136/ard.61.3.213
76. El-Tahan RR, Ghoneim AM, El-Mashad N. TNF-α gene polymorphisms and expression. SpringerPlus 2016; 5 (1): 1508. doi: 10.1186/s40064-016-3197-y
77. Li P, Schwarz EM. The TNF-alpha transgenic mouse model of inflammatory arthritis. Seminars in Immunopathology 2003; 25 (1): 19-33. doi: 10.1007/s00281-003-0125-3
78. Nelson GW, Martin MP, Gladman D, Wade J, Trowsdale J et al. Cutting edge: heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in psoriatic arthritis. Journal of Immunology 2004; 173 (7): 4273-4276. doi: 10.4049/ jimmunol.173.7.4273
79. Yen JH, Moore BE, Nakajima T, Scholl D, Schaid DJ et al. Major histocompatibility complex class I-recognizing receptors are disease risk genes in rheumatoid arthritis. Journal of Experimental Medicine 2001; 193 (10): 1159-1167. doi: 10.1084/jem.193.10.1159
80. Schurich A, Raine C, Morris V, Ciurtin C. The role of IL12/23 in T cell-related chronic inflammation: implications of immunodeficiency and therapeutic blockade. Rheumatology (Oxford) 2018; 57 (2): 246-254. doi: 10.1093/rheumatology/ kex186
81. Filer C, Ho P, Smith RL, Griffiths C, Young HS et al. Investigation of association of the IL12B and IL23R genes with psoriatic arthritis. Arthritis & Rheumatism 2008; 58 (12): 3705-3709. doi: 10.1002/art.24128
82. Eirís N, González-Lara L, Santos-Juanes J, Queiro R, Coto E et al. Genetic variation at IL12B, IL23R and IL23A is associated with psoriasis severity, psoriatic arthritis and type 2 diabetes mellitus. Journal of Dermatological Science 2014; 75 (3): 167- 172. doi: 10.1016/j.jdermsci.2014.05.010
83. Sarin R, Wu X, Abraham C. Inflammatory disease protective R381Q IL23 receptor polymorphism results in decreased primary CD4+ and CD8+ human T-cell functional responses. Proceedings of the National Academy of Sciences of the United States of America 2011; 108 (23): 9560-9565. doi: 10.1073/ pnas.1017854108
84. Tabatabaei-Panah PS, Moravvej H, Delpasand S, Jafari M, Sepehri S et al. IL12B and IL23R polymorphisms are associated with alopecia areata. Genes & Immunity 2020; 21 (3): 203-210. doi: 10.1038/s41435-020-0100-1
85. Sánchez E, Rueda B, Callejas JL, Sabio JM, Ortego-Centeno N et al. Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus. Tissue Antigens 2007; 70 (3): 233-237. doi: 10.1111/j.1399- 0039.2007.00881.x
86. Chang M, Saiki RK, Cantanese JJ, Lew D, Van der Helm-van Mil AH et al. The inflammatory disease-associated variants in IL12B and IL23R are not associated with rheumatoid arthritis. Arthritis & Rheumatism 2008; 58 (6): 1877-1881. doi: 10.1002/ art.23492
87. Bowes J, Eyre S, Flynn E, Ho P, Salah S et al. Evidence to support IL-13 as a risk locus for psoriatic arthritis but not psoriasis vulgaris. Annals of the Rheumatic Diseases 2011; 70 (6): 1016-1019. doi: 10.1136/ard.2010.143123
88. Eder L, Chandran V, Pellett F, Pollock R, Shanmugarajah S et al. IL13 gene polymorphism is a marker for psoriatic arthritis among psoriasis patients. Annals of the Rheumatic Diseases 2011; 70 (9): 1594-1598. doi: 10.1136/ard.2010.147421
89. Spadaro A, Rinaldi T, Riccieri V, Valesini G, Taccari E. Interleukin 13 in synovial fluid and serum of patients with psoriatic arthritis. Annals of the Rheumatic Diseases 2002; 61 (2): 174-176. doi: 10.1136/ard.61.2.174
90. Mao YM, Zhao CN, Leng J, Leng RX, Ye DQ et al. Interleukin-13: a promising therapeutic target for autoimmune disease. Cytokine & Growth Factor Reviews 2019; 45: 9-23. doi: 10.1016/j.cytogfr.2018.12.001
91. Wang R, Lu YL, Huang HT, Qin HM, Lan Y, Wang JL et al. Association of interleukin 13 gene polymorphisms and plasma IL 13 level with risk of systemic lupus erythematosus. Cytokine 2018; 104: 92-97. doi: 10.1016/j.cyto.2017.09.034
92. Julià A, López-Longo FJ, Pérez Venegas JJ, Bonàs-Guarch S, Olivé À et al. Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus. Arthritis Research & Therapy 2018; 20 (1): 100. doi: 10.1186/ s13075-018-1604-1
93. Shamilov R, Aneskievich BJ. TNIP1 in autoimmune diseases: regulation of toll-like receptor signaling. Journal of Immunology Research 2018; 2018: 3491269. doi: 10.1155/2018/3491269
94. Ramirez VP, Gurevich I, Aneskievich BJ. Emerging roles for TNIP1 in regulating post-receptor signaling. Cytokine & Growth Factor Reviews 2012; 23 (3): 109-118. doi: 10.1016/j. cytogfr.2012.04.002
95. Aeschlimann FA, Batu ED, Canna SW, Go E, Gül A et al. A20 haploinsufficiency (HA20): clinical phenotypes and disease course of patients with a newly recognised NF-kB-mediated autoinflammatory disease. Annals of the Rheumatic Diseases 2018; 77 (5): 728-735. doi: 10.1136/annrheumdis-2017-212403
96. Dainichi T, Matsumoto R, Mostafa A, Kabashima K. Immune control by TRAF6-mediated pathways of epithelial cells in the EIME (epithelial immune microenvironment). Frontiers in Immunology 2019; 10: 1107. doi: 10.3389/fimmu.2019.01107
97. Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF et al. The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nature Immunology 2007; 8 (3): 247-256. doi: 10.1038/ni1439
98. Hüffmeier U, Uebe S, Ekici AB, Bowes J, Giardina E et al. Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis. Nature Genetics 2010; 42 (11): 996-999. doi: 10.1038/ng.688
99. Li Z, Rotival M, Patin E, Michel F, Pellegrini S. Two common disease-associated TYK2 variants impact exon splicing and TYK2 dosage. PLoS One 2020; 15 (1): e0225289. doi: 10.1371/ journal.pone.0225289
100. Enerbäck C, Sandin C, Lambert S, Zawistowski M, Stuart PE et al. The psoriasis-protective TYK2 I684S variant impairs IL12 stimulated pSTAT4 response in skin-homing CD4+ and CD8+ memory T-cells. Scientific Reports 2018; 8 (1): 7043. doi: 10.1038/s41598-018-25282-2
101. Pollock RA, Abji F, Gladman DD. Epigenetics of psoriatic disease: a systematic review and critical appraisal. Journal of Autoimmunity 2017; 78: 29-38. doi: 10.1016/j.jaut.2016.12.002
102. Quintero-Ronderos P, Montoya-Ortíz G. Epigenetics and autoimmune diseases. In: Anaya JM, Shoenfeld Y, RojasVillarraga A, Levy RA, Cervera R (editors). Autoimmunity: From Bench to Bedside. Bogota, DC, Colombia: El Rosario University Press; 2013. pp. 351-372.
103. Pollock RA, Zaman L, Chandran V, Gladman DD. Epigenomewide analysis of sperm cells identifies IL22 as a possible germ line risk locus for psoriatic arthritis. PLoS One 2019; 14 (2): e0212043. doi: 10.1371/journal.pone.0212043
104. Verma A, Bang L, Miller JE, Zhang Y, Lee MTM et al. Humandisease phenotype map derived from PheWAS across 38,682 individuals. American Journal of Human Genetics 2019; 104 (1): 55-64. doi: 10.1016/j.ajhg.2018.11.006
105. Pelosi A, Lunardi C, Fiore PF, Tinazzi E, Patuzzo G et al. MicroRNA expression profiling in psoriatic arthritis. BioMed Research International 2018; 2018: 7305380. doi: 10.1155/2018/7305380
106. Casciaro M, Di Salvo E, Brizzi T, Rodolico C, Gangemi S. Involvement of miR-126 in autoimmune disorders. Clinical and Molecular Allergy 2018; 16: 11. doi: 10.1186/s12948-018- 0089-4
107. Qu Z, Li W, Fu B. MicroRNAs in autoimmune diseases. BioMed Research International 2014; 2014: 527895. doi: 10.1155/2014/527895
108. Ritchlin CT, McGonalge D. Etiology and pathogenesis of psoriatic arthritis. In: Hochberg MC, Gravallese EM, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH (editors). Rheumatology. 7th ed. Philadelphia, PA, USA: Elsevier; 2019. pp. 1060-1070.
109. Veale DJ, Ritchlin C, FitzGerald O. Immunopathology of psoriasis and psoriatic arthritis. Annals of the Rheumatic Diseases 2005; 64 Suppl 2 (Suppl 2): ii26-ii29. doi: 10.1136/ ard.2004.031740
110. Tassiulas I, Duncan SR, Centola M, Theofilopoulos AN, Boumpas DT. Clonal characteristics of T cell infiltrates in skin and synovium of patients with psoriatic arthritis. Human Immunology 1999; 60 (6): 479-491. doi: 10.1016/s0198- 8859(99)00034-8
111. Diani M, Casciano F, Marongiu L, Longhi M, Altomare A et al. Increased frequency of activated CD8+ T cell effectors in patients with psoriatic arthritis. Scientific Reports 2019; 9 (1): 10870. doi: 10.1038/s41598-019-47310-5
112. Liu Y, Jarjour W, Olsen N, Zheng SG. Traitor or warriorTreg cells sneaking into the lesions of psoriatic arthritis. Clinical Immunology 2020; 215: 108425. doi: 10.1016/j. clim.2020.108425
113. Conigliaro P, Chimenti MS, Triggianese P, Sunzini F, Novelli L et al. Autoantibodies in inflammatory arthritis. Autoimmunity Reviews 2016; 15 (7): 673-683. doi: 10.1016/j.autrev.2016.03.003
114. Chimenti MS, Triggianese P, Nuccetelli M, Terracciano C, Crisanti A et al. Auto-reactions, autoimmunity and psoriatic arthritis. Autoimmunity Reviews 2015; 14 (12): 1142-1146. doi: 10.1016/j.autrev.2015.08.003
115. Dolcino M, Lunardi C, Ottria A, Tinazzi E, Patuzzo G et al. Crossreactive autoantibodies directed against cutaneous and joint antigens are present in psoriatic arthritis. PLoS One 2014; 9 (12): e115424. doi: 10.1371/journal.pone.0115424
116. Yuan Y, Qiu J, Lin ZT, Li W, Haley C et al. Identification of novel autoantibodies associated with psoriatic arthritis. Arthritis & Rheumatology 2019; 71 (6): 941-951. doi: 10.1002/art.40830
117. Gestermann N, Di Domizio J, Lande R, Demaria O, Frasca L et al. Netting neutrophils activate autoreactive b cells in lupus. Journal of Immunology 2018; 200 (10): 3364-3371. doi: 10.4049/jimmunol.1700778
118. Chiang CC, Cheng WJ, Korinek M, Lin CY, Hwang TL. Neutrophils in psoriasis. Frontiers in Immunology 2019; 10: 2376. doi: 10.3389/fimmu.2019.02376
119. Fallahi P, Ferrari SM, Ruffilli I, Elia G, Miccoli M et al. Increased incidence of autoimmune thyroid disorders in patients with psoriatic arthritis: a longitudinal follow-up study. Immunologic Research 2017; 65 (3): 681-686. doi: 10.1007/s12026-017-8900-8
120. Antonelli A, Delle Sedie A, Fallahi P, Ferrari SM, Maccheroni M et al. High prevalence of thyroid autoimmunity and hypothyroidism in patients with psoriatic arthritis. The Journal of Rheumatology 2006; 33 (10): 2026-2028.
121. Korkus D, Gazitt T, Cohen AD, Feldhamer I, Lavi I et al. Increased prevalence of lupus co-morbidity in patients with psoriatic arthritis: a population-based case-controlled study. The Journal of Rheumatology 2021; 48 (2): 207-213. doi: 10.3899/jrheum.190940
122. Whaley K, Chisholm DM, Williamson J, Dick WC, Nuki G et al. Sjögren’s syndrome in psoriatic arthritis, ankylosing spondylitis and Reiter’s syndrome. Acta Rheumatologica Scandinavica 1971; 17 (2): 105-114. doi: 10.3109/rhe1.1971.17. issue-1-4.16
123. Zohar A, Cohen AD, Bitterman H, Feldhamer I, GreenbergDotan S et al. Gastrointestinal comorbidities in patients with psoriatic arthritis. Clinical Rheumatology 2016; 35 (11): 2679- 2684. doi: 10.1007/s10067-016-3374-y
124. Lindqvist U, Rudsander A, Boström A, Nilsson B, Michaëlsson G. IgA antibodies to gliadin and coeliac disease in psoriatic arthritis. Rheumatology (Oxford) 2002; 41 (1): 31-37. doi: 10.1093/rheumatology/41.1.31
125. Liewluck T, Ernste FC, Tracy JA. Frequency and spectrum of myopathies in patients with psoriasis. Muscle & Nerve 2013; 48 (5): 716-721. doi: 10.1002/mus.23812
126. Tselios K, Yap KS, Pakchotanon R, Polachek A, Su J et al. Psoriasis in systemic lupus erythematosus: a single-center experience. Clinical Rheumatology 2017; 36 (4): 879-884. doi: 10.1007/s10067-017-3566-0
127. Watad A, Bragazzi NL, McGonagle D, Damiani G, Comaneshter D et al. Systemic sclerosis is linked to psoriasis and may impact on patients’ survival: a large cohort study. Journal of Clinical Medicine 2019; 8 (4): 521. doi: 10.3390/jcm8040521
128. Liu CY, Tung TH, Lee CY, Chang KH, Wang SH et al. association of multiple sclerosis with psoriasis: a systematic review and meta-analysis of observational studies. American Journal of Clinical Dermatology 2019; 20 (2): 201-208. doi: 10.1007/s40257-018-0399-9
129. Jimenez-Boj E, Stamm TA, Sadlonova M, Rovensky J, Raffayová H et al. Rituximab in psoriatic arthritis: an exploratory evaluation. Annals of the Rheumatic Diseases 2012; 71 (11): 1868-1871. doi: 10.1136/annrheumdis-2012-201897
130. Larosa M, Zen M, Gatto M, Jesus D, Zanatta E et al. IL12 and IL-23/Th17 axis in systemic lupus erythematosus. Experimental Biology and Medicine (Maywood) 2019; 244 (1): 42-51. doi: 10.1177/1535370218824547
131. Silfvast-Kaiser AS, Homan KB, Mansouri B. A narrative review of psoriasis and multiple sclerosis: links and risks. Psoriasis (Auckland) 2019; 9: 81-90. doi: 10.2147/PTT.S186637

APA	emmungil h, İlgen U, Direskeneli H (2021). Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. , 1601 - 1614. 10.3906/sag-2011-235
Chicago	emmungil hakan,İlgen Ufuk,Direskeneli Haner Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. (2021): 1601 - 1614. 10.3906/sag-2011-235
MLA	emmungil hakan,İlgen Ufuk,Direskeneli Haner Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. , 2021, ss.1601 - 1614. 10.3906/sag-2011-235
AMA	emmungil h,İlgen U,Direskeneli H Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. . 2021; 1601 - 1614. 10.3906/sag-2011-235
Vancouver	emmungil h,İlgen U,Direskeneli H Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. . 2021; 1601 - 1614. 10.3906/sag-2011-235
IEEE	emmungil h,İlgen U,Direskeneli H "Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects." , ss.1601 - 1614, 2021. 10.3906/sag-2011-235
ISNAD	emmungil, hakan vd. "Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects". (2021), 1601-1614. https://doi.org/10.3906/sag-2011-235

APA	emmungil h, İlgen U, Direskeneli H (2021). Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. Turkish Journal of Medical Sciences, 51(4), 1601 - 1614. 10.3906/sag-2011-235
Chicago	emmungil hakan,İlgen Ufuk,Direskeneli Haner Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. Turkish Journal of Medical Sciences 51, no.4 (2021): 1601 - 1614. 10.3906/sag-2011-235
MLA	emmungil hakan,İlgen Ufuk,Direskeneli Haner Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. Turkish Journal of Medical Sciences, vol.51, no.4, 2021, ss.1601 - 1614. 10.3906/sag-2011-235
AMA	emmungil h,İlgen U,Direskeneli H Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. Turkish Journal of Medical Sciences. 2021; 51(4): 1601 - 1614. 10.3906/sag-2011-235
Vancouver	emmungil h,İlgen U,Direskeneli H Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects. Turkish Journal of Medical Sciences. 2021; 51(4): 1601 - 1614. 10.3906/sag-2011-235
IEEE	emmungil h,İlgen U,Direskeneli H "Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects." Turkish Journal of Medical Sciences, 51, ss.1601 - 1614, 2021. 10.3906/sag-2011-235
ISNAD	emmungil, hakan vd. "Autoimmunity in psoriatic arthritis: pathophysiological and clinical aspects". Turkish Journal of Medical Sciences 51/4 (2021), 1601-1614. https://doi.org/10.3906/sag-2011-235