Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Aita, Ada (2017) Genetics in TNF-TNFR pathway: a complex network causing spondyloarthritis and conditioning response to therapy. [Tesi di dottorato]

Full text disponibile come:

[img]
Anteprima
Documento PDF (Ada_Aita_Tesi) - Versione accettata
4Mb

Abstract (inglese)

Background. The seronegative spondyloarthritis (SpA) are a group of chronic inflammatory diseases resulting from a complex interplay among genetic background (mainly represented by HLA-B27) and environmental factors, that leads to the activation of autoinflammation and the dysregulation of the immune-system.
In many cases, an early diagnosis and an appropriate monitoring of disease activity can be difficult because of the overlap of clinical features. Furthermore, because of the indices of inflammation, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are in the normal range in at least half of SpA patients with a clear expression of disease activity, a delay in diagnosis and consequently in treatment in these patients has been documented. This imparts a tremendous symptomatic burden and loss of function in these patients during the productive years of life. For all these reasons, much attention is currently devoted to the identification of biochemical and genetic biomarkers to be used in the diagnosis as well as prognostic factors in evaluating the treatment effectiveness.
Among the genetic predisposing factors, a well-known role is that of HLA-B27, which contributes however to only 20–30% of the total heritability, whereas the whole major histocompatibility complex (MHC) accounts for about 40–50% of the genetic risk of developing SpA. This suggested that other genes are involved in pathogenetic mechanism. In fact, in addition to HLA-B27, a number of genetic factors in both, MHC and non-MHC locus, have been claimed to play a role in pathogenesis of SpA.
In this context, because of TNF-α is primarily involved in the propagation and perpetuation of inflammation in SpA, the study of TNF-α genetic is of great interest. Several polymorphisms (SNPs) in genes involved in TNF-α signalling, as TNFA, TNFSF15, TNFR1 and TRADD genes, have been identified as associated with SpA, even if results are controversial. Of great interest are also variants in MEFV gene, involved in the pathogenesis of the autoinflammatory disorder Familial Mediterranean Fever (FMF). Recent studies have shown that the SpA, and in particular the ankylosing spondylitis (AS), are very common among patients affected by FMF and that these patients can present with AS as a sole manifestation.
The present study, conducted in a cohort of 91 SpA patients and 223 controls, coming from a North-East Italian region, was aimed to identify biohumoral (biochemical and haematological) and genetic factors to support the diagnostic and prognostic (response to therapy) work-up of SpA diseases. In particular, in addition to biochemical and haematological indices, we investigated whether SNPs in the promoter region of TNFA, or SNPs in the autoinflammatory TNFRSF1A and MEFV genes, might concur with HLA-B27 in enhancing the risk of developing SpA disease and/or in predicting the response to anti-TNFα drugs.
Methods. The study population comprised 91 patients with a diagnosis of SpA (mean age ± standard deviation: 52.1 ± 12.5 years; 57 males, 34 females) and 223 blood donors (mean age ± standard deviation: 46 ± 11 years; 146 males, 77 females) coming from Veneto Region, a North-East Italian region. Among patients, 36 had a diagnosis of AS and 55 patients of psoriatic arthritis (PsA), which were based on New York and CASPAR criteria respectively. The protocol of this study was approved by the Local Institutional Ethic Committee of University-Hospital of Padua, Italy (Prot.n. 3024P/13), and all participants gave written informed consent before entering the study.
Demographic and physiological data, medical and familial history data were collected for each participant. Blood samples were collected and complete blood count, CRP, ESR, uric acid, prealbumin, alanina aminotransferase (ALT) and glucose were evaluated.
Direct sequencing of MEFV (exons 2,3,5 and 10) and TNFRSF1A (exons 2,3,4 and 6) genes were performed. HLA-B27 and TNFA polymorphisms (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) were assayed by Real Time-PCR. HLA-CW6 allele presence was analysed by molecular genetic testing using a commercially available CE-IVD microarray. Statistical analysis was performed using STATA software (version 13.1).
Results. An higher number of circulating polymorphonuclear cells and higher CRP levels could be detected in SpA patients with respect to controls, and in PsA higher levels of ALT could be observed with respect not only to controls but also to AS. Anyway these indices were not highly elevated and often comprised within the reference intervals.
As expected, HLA-B27 was associated with AS (χ2=120.1; p<0.0001). Although a slightly higher frequency of HLA-CW6 carriers was observed among patients with AS (about 6%) or PsA (about 13%) with respect to controls (about 4%), the difference was not statistically significant.
Any single studied TNFA SNP was not associated with SpA diagnosis, nor with AS or PsA considered singly. The haplotypes deriving from the pairwise combinations of the five studied SNPs were also statistically inferred. The most frequent haplotypes in controls were selected as references, and only the haplotype -1031C/-308G was significantly associated with AS (p=0.015) exerting in this disease a protective role (Odds Ratio: 0.43; Confidence Interval 95%: 0.22-0.85).
Three SNPs were identified in TNFRSF1A gene and among them, only the R92Q (Minor Allele Frequency- MAF=0.034) and the c.625+10A>G (MAF=0.479) were selected for their potential functional implications. Both SNPs were not associated with the presence of SpA (χ2=1.073 and p=0.300 for R92Q; χ2=4.721 and p=0.094 for c.625+10A>G), but c.625+10A>G was associated with the response to anti-TNF therapy, assessed by BASDAI score lower /equal or higher than 4 at 10 months (p=0.031).
Twenty-one SNPs were identified in MEFV gene and among them, 10 with a known potential functional significance. Variant alleles were extremely rare in our population (MAF<0.025) except for R202Q (MAF=0.27). None was associated with SpA diagnosis (p>0.05).
Conclusions. In conclusion the results of this study indicate the relevant role of TNF-TNFR pathway genetics in the complex network causing SpA and conditioning response to therapy. TNFA was shown to be a predisposing factor for SpA, but mainly for AS, among Italian patients, while genetics of the autoinflammatory gene MEFV appears of no impact in this setting. The haplotype resulting from TNFA-1031C/-308G, potentially associated with lower TNF-α production, exerts a protective role in AS, while the TNFRSF1A c.625+10A>G polymorphism emerged as a potential predictor of response to anti- TNFα therapy.






Abstract (italiano)

Introduzione. Le spondiloartriti sieronegative (SpA) sono un gruppo di malattie infiammatorie croniche risultanti da una complessa interazione tra fattori genetici (tra cui, HLA-B27 è il maggior predisponente) e ambientali. Ed è tale interazione ad indurre l'attivazione di processi autoinfiammatori e la disregolazione del sistema immunitario caratterizzanti la malattia.
In molti casi, una diagnosi precoce ed un adeguato monitoraggio dell’ attività di malattia risultano difficili a causa della sovrapposizione delle caratteristiche cliniche tra le diverse forme. Il ritardo nella diagnosi e conseguentemente nel trattamento, è inoltre dovuto al fatto che, gli indici d’infiammazione comunemente utilizzati nella pratica clinica, la velocità di eritrosedimentazione (VES) ed la proteina C-reattiva (PCR), sono nella norma in almeno metà dei pazienti con chiara espressione dell’attività di malattia. Il ritardo nella diagnosi conferisce a questi pazienti un carico sintomatico importante ed una perdita di funzione durante gli anni di vita produttiva. Pertanto, forte attenzione è attualmente rivolta all’identificazione di marcatori biochimici e genetici utili alla diagnosi e di fattori prognostici necessari a valutare l'efficacia del trattamento.
Tra i fattori genetici predisponenti, è noto il ruolo di HLA-B27, che contribuisce però solo per il 20-30% all'ereditarietà totale, mentre il complesso maggiore di istocompatibilità (MHC) rappresenta circa il 40-50% del rischio genetico di sviluppare la patologia. Questo dato ha suggerito il probabile coinvolgimento di altri geni nel meccanismo patogenetico. Studi di associazione genetica hanno permesso di identificare un certo numero di altri geni, associati alla patologia, sia nel locus MHC che in altri loci.
In questo contesto, di grande interesse è lo studio della genetica di TNF-α, considerato il ruolo di tale citochina nel propagare e perdurare dell'infiammazione. Sebbene numerosi studi abbiano dimostrato l’associazione tra i polimorfismi di geni coinvolti nella via del segnale del TNF-α (es. TNFA, TNFSF15, TNFR1 e TRADD) e la patologia di SpA, i risultati sono discordanti. Di grande interesse sono anche le varianti del MEFV gene, coinvolto nella patogenesi della malattia autoinfiammatoria Febbre Mediterranea Familiare (FMF). Studi recenti hanno, infatti, dimostrato che le SpA, ed in particolare la spondilite anchilosante (AS), sono molto comuni tra i pazienti affetti da FMF e che questi pazienti possono presentarsi con AS come unica manifestazione.
Questo studio, condotto su 91 pazienti e 223 controlli, provenienti da una regione italiana del Nord-Est, si propone di identificare fattori bioumorali (biochimici ed ematologici) e genetici al fine di supportare i processi diagnostici e prognostici (risposta alla terapia). In particolare, oltre ai parametri biochimici ed ematologici, è stato valutato se polimorfismi nella regione del promotore del gene TNFA, o dei geni TNFRSF1A e MEFV, possano concorrere con l’allele HLA-B27 all’aumento del rischio di sviluppare la malattia e/o nel predire la risposta agli inibitori del TNF-α.
Metodi. La popolazione studiata comprendeva 91 pazienti con diagnosi di SpA (età media ± deviazione standard: 52.1 ± 12.5 anni; 57 maschi, 34 femmine) e 223 donatori di sangue (età media ± deviazione standard: 46 ± 11 anni; 146 maschi, 77 femmine) provenienti dalla Regione Veneto, una regione italiana del Nord-Est. Tra i pazienti, 36 presentavano AS e 55 artrite psoriasica (PsA), con diagnosi formulata sulla base dei criteri rispettivamente di New York e CASPAR. Il protocollo di questo studio è stato approvato dal Comitato Etico Istituzionale locale dell’Università-Azienda Ospedaliera di Padova, Italia (Prot.n. 3024P / 13), e tutti i soggetti arruolati hanno firmato un consenso informato prima di partecipare allo studio.
Per ciascun soggetto arruolato, sono stati raccolti i dati demografici e fisiologici, la storia clinica e familiare. Sono stati raccolti poi, campioni di sangue, al fine di valutare l’emocromo e la VES, e di determinare i livelli di PCR, acido urico, prealbumina, alanina aminotransferasi (ALT) e glucosio.
L’analisi molecolare dei geni MEFV (esoni 2,3,5 e 10) e TNFRSF1A (esoni 2,3,4 e 6) è avvenuta mediante sequenziamento diretto. La determinazione degli alleli HLA-B27 e dei polimorfismi del gene TNFA (-1031T>C;-857C>T;-376G>A;-308G>A;-238G>A) è stata condotta mediante PCR in Real-Time. La determinazione degli alleli HLA-CW6 è avvenuta mediante un test genetico molecolare CE-IVD, disponibile in commercio, che adotta la tecnologia microarray. L’analisi statistica è stata effettuata utilizzando il software STATA (versione 13.1).
Risultati. Un maggior numero di cellule polimorfonucleate circolanti e livelli di PCR più elevati sono stati rilevati nei pazienti affetti da SpA rispetto ai controlli. Inoltre, i pazienti affetti da PsA hanno mostrato livelli più elevati di ALT, non solo rispetto ai controlli, ma anche rispetto a pazienti affetti da AS. In ogni caso tali indici non erano molto elevati e spesso risultavano compresi entro gli intervalli di riferimento.
Come atteso, gli alleli HLA-B27 sono risultati associati all’AS (χ2=120.1; p<0.0001). Sebbene una frequenza leggermente maggiore degli alleli HLA-CW6 sia stata osservata tra i pazienti con AS (circa il 6%) o PsA (circa il 13%) rispetto ai controlli (circa 4%), la differenza non è risultata essere statisticamente significativa.
Nessuno dei polimorfismi del gene TNFA è risultato singolarmente associato alla diagnosi SpA, né a quella di AS o PsA, se valutate indipendentemente. Sono stati, poi, statisticamente dedotti gli aplotipi derivanti dalle coppie di combinazioni dei cinque polimorfismi studiati. Gli aplotipi più frequenti nei controlli sono stati selezionati come aplotipi di riferimento, e solo l’aplotipo -1031C/-308G è risultato significativamente associato con l’AS (p=0.015) esercitando in questa malattia un ruolo protettivo (odds ratio: 0.43; intervallo di confidenza al 95%: 0.22- 0.85).
Tre polimorfismi sono stati identificati nel gene TNFRSF1A e tra questi, solo i polimorfismi R92Q (Frequenza dell’allele minore- MAF = 0.034) e c.625 + 10A> G (MAF = 0.479) sono stati selezionati a causa del potenziale ruolo funzionale. Entrambi i polimorfismi non sono risultati associati con la diagnosi di SpA (χ2 = 1.073 e p = 0.300 per R92Q; χ2 = 4.721 e p = 0.094 per c.625 + 10A> G). Il polimorfismo c.625 + 10A> G è però, risultato essere associato con la risposta alla terapia con anti-TNF, valutato sulla base di un punteggio BASDAI inferiore / uguale o superiore a 4, a 10 mesi dall’inizio della terapia (p = 0.031).
Ventuno polimorfismi sono stati identificati nel gene MEFV e tra questi, 10 noti per il potenziale significato funzionale. Tali varianti alleliche sono risultate estremamente rare nella nostra popolazione (MAF <0.025) ad eccezione di R202Q (MAF = 0.27). Nessun polimorfismo è risultato essere associato con la diagnosi SpA (p> 0.05).
Conclusioni. In conclusione, i risultati di questo studio suggeriscono il ruolo rilevante della genetica della via del segnale TNF-TNFR nel complesso sistema che induce la patogenesi di SpA e condiziona la risposta alla terapia. Il gene TNFA, nella popolazione oggetto di studio, si è dimostrato un fattore predisponente per lo sviluppo di SpA, ma soprattutto di AS. Al contrario, la genetica del gene MEFV non sembra mostrare alcun impatto in questo gruppo di malattie. L'aplotipo TNFA-1031C/-308G, potenzialmente associato alla produzione di livelli più bassi di TNF-α, sembra esercitare un ruolo protettivo nella patogenesi di AS, mentre è emerso che il polimorfismo c.625 TNFRSF1A + 10A> G costituisce un potenziale fattore predittivo di risposta alla terapia con anti-TNFα.

Statistiche Download - Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Punzi, Leonardo
Dottorato (corsi e scuole):Ciclo 29 > Corsi 29 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI
Data di deposito della tesi:31 Gennaio 2017
Anno di Pubblicazione:31 Gennaio 2017
Parole chiave (italiano / inglese):Spondyloarthritis
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/16 Reumatologia
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina
Codice ID:10237
Depositato il:03 Nov 2017 10:23
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

1. Moll JM, Haslock I, Macrae IF, Wright V. Associations between ankylosing spondylitis, psoriatic arthritis, Reiter's disease, the intestinal arthropathies, and Behcet's syndrome. Medicine 1974;53:343-64. Cerca con Google

2. Giovannini L, Orlandi M, Lodato C, Cioffi E, Tenti S, Bardelli M, et al. One year in review 2015: spondyloarthritis. Clin Exp Rheumatol 2015;33:769-78. Cerca con Google

3. Garg N, van den Bosch F, Deodhar A. The concept of spondyloarthritis: where are we now? Best Pract Res Clin Rheumatol 2014;28:663-72. Cerca con Google

4. Dougados M, Baeten D. Spondyloarthritis. Lancet 2011;377:2127-37. Cerca con Google

5. Dougados M, van der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A, et al. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum 1991;34:1218-27. Cerca con Google

6. Amor B, Dougados M, Mijiyawa M. Criteria of the classification of spondylarthropathies. Rev Rhum Mal Osteoartic 1990;57:85-9. Cerca con Google

7. Rudwaleit M, van der Heijde D, Landewé R, Akkoc N, Brandt J, Chou CT, et al. The Assessment of SpondyloArthritis International Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011;70:25-31. Cerca con Google

8. Stolwijk C, van Onna M, Boonen A, van Tubergen A. Global Prevalence of Spondyloarthritis: A Systematic Review and Meta-Regression Analysis. Arthritis Care Res 2016;68:1320-31. Cerca con Google

9. De Angelis R, Salaffi F, Grassi W. Prevalence of spondyloarthropathies in an Italian population sample: a regional community-based study. Scand J Rheumatol 2007;36:14-21. Cerca con Google

10. Feldtkeller E, Khan MA, van der Heijde D, van der Linden S, Braun J. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int 2003;23:61-6. Cerca con Google

11. Mohan C, Assassi S. Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity? BMJ 2015;351:h5079. Cerca con Google

12. Zochling J. Measures of symptoms and disease status in ankylosing spondylitis: Ankylosing Spondylitis Disease Activity Score (ASDAS), Ankylosing Spondylitis Quality of Life Scale (ASQoL), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Global Score (BAS-G), Bath Ankylosing Spondylitis Metrology Index (BASMI), Dougados Functional Index (DFI), and Health Assessment Questionnaire for the Spondylarthropathies (HAQ-S). Arthritis Care Res 2011;63 Suppl 11:S47-58. Cerca con Google

13. Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 1994;21:2286-91. Cerca con Google

14. Godfrin-Valnet M, Prati C, Puyraveau M, Toussirot E, Letho-Gyselink H, Wendling D. Evaluation of spondylarthritis activity by patients and physicians: ASDAS, BASDAI, PASS, and flares in 200 patients. Joint Bone Spine 2013;80:393-8. Cerca con Google

15. Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. Assessment of SpondyloArthritis international Society.Development of an ASAS-endorsed disease activity score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:18-24. Cerca con Google

16. Van der Heijde D, Lie E, Kvien TK, Sieper J, Van den Bosch F, Listing J, et al. Assessment of SpondyloArthritis international Society (ASAS). ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis. Ann Rheum Dis 2009;68:1811-8. Cerca con Google

17. Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, Landewé R, van ver Tempel H, Mielants H, et al. Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis 2003;62:127-32. Cerca con Google

18. Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44-8. Cerca con Google

19. Downie WW, Leatham PA, Rhind VM, Pickup ME, Wright V. The visual analogue scale in the assessment of grip strength. Ann Rheum Dis 1978;37:382-4. Cerca con Google

20. Downie WW, Leatham PA, Rhind VM, Wright V, Branco JA, Anderson JA. Studies with pain rating scales. Ann Rheum Dis 1978;37:378-81. Cerca con Google

21. Calin A, Garrett S, Whitelock H, Kennedy LG, O'Hea J, Mallorie P, Jenkinson T.A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994;21:2281-5. Cerca con Google

22. Daltroy LH, Larson MG, Roberts NW, Liang MH. A modification of the Health Assessment Questionnaire for the spondyloarthropathies. J Rheumatol 1990;17:946-50. Erratum in: J Rheumatol 1991;18:305. Cerca con Google

23. Jenkinson TR, Mallorie PA, Whitelock HC, Kennedy LG, Garrett SL, Calin A. Defining spinal mobility in ankylosing spondylitis (AS). The Bath AS Metrology Index. J Rheumatol 1994;21:1694-8. Cerca con Google

24. Song IH, Poddubnyy DA, Rudwaleit M, Sieper J. Benefits and risks of ankylosing spondylitis treatment with nonsteroidal antiinflammatory drugs. Arthritis Rheum 2008;58:929-38. Cerca con Google

25. Braun J, Sieper J. Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-alpha therapy and other novel approaches. Arthritis Res 2002;4:307-21. Cerca con Google

26. Braun J, Brandt J, Listing J, Rudwaleit M, Sieper J. Biologic therapies in the spondyloarthritis: new opportunities, new challenges. Curr Opin Rheumatol 2003;15:394-407. Cerca con Google

27. Prince DS, McGuigan LE, McGirr EE. Working life and physical activity in ankylosing spondylitis pre and post anti-tumor necrosis factor-alpha therapy. Int J Rheum Dis 2014;17:165-72. Cerca con Google

28. Baeten D, Kruithof E, Van den Bosch F, Van den Bossche N, Herssens A, Mielants H, et al. Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease? Ann Rheum Dis 2003;62:829-34. Cerca con Google

29. Van der Heijde D, Landewé R, Einstein S, Ory P, Vosse D, Ni L, et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008;58:1324-31. Cerca con Google

30. Braun J, Sieper J. Ankylosing spondylitis. Lancet 2007;369:1379-90. Cerca con Google

31. Daikh DI, Chen PP. Advances in managing ankylosing spondylitis. F1000Prime Rep 2014;6:78. Cerca con Google

32. Smith JA. Update on ankylosing spondylitis: current concepts in pathogenesis. Curr Allergy Asthma Rep 2015;15:489. Cerca con Google

33. Van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361-8. Cerca con Google

34. Khan MA. Polymorphism of HLA-B27: 105 subtypes currently known. Curr Rheumatol Rep 2013;15:362. Cerca con Google

35. Robinson PC, Brown MA. Genetics of ankylosing spondylitis. Mol Immunol 2014;57:2-11. Cerca con Google

36. Braun J, van den Berg R, Baraliakos X, Boehm H, Burgos-Vargas R, Collantes-Estevez E, et al. 2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis. Ann Rheum Dis 2011;70:896-904. Cerca con Google

37. Van den Berg R, Baraliakos X, Braun J, van der Heijde D. First update of the current evidence for the management of ankylosing spondylitis with non-pharmacological treatment and non-biologic drugs: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis. Rheumatology 2012;51:1388-96. Cerca con Google

38. Baraliakos X, van den Berg R, Braun J, van der Heijde D. Update of the literature review on treatment with biologics as a basis for the first update of the ASAS/EULAR management recommendations of ankylosing spondylitis. Rheumatology 2012;51:1378-87. Cerca con Google

39. Gladman DD. Psoriatic arthritis. Dermatol Ther 2009;22:40-55. Cerca con Google

40. Wright V, Moll JMH. Psoriatric Arthritis. In seronegative polyarthritis. Amsterdam: North Holland Publishing Co., 1976: 169–235. Cerca con Google

41. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. CASPAR Study Group. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006;54:2665-73. Cerca con Google

42. Cervini C, Leardini G, Mathieu A, Punzi L, Scarpa R. Psoriatic arthritis: epidemiological and clinical aspects in a cohort of 1.306 Italian patients. Reumatismo 2005;57:283-90. Cerca con Google

43. Punzi L, Pianon M, Rossini P, Schiavon F, Gambari PF. Clinical and laboratory manifestations of elderly onset psoriatic arthritis: a comparison with younger onset disease. Ann Rheum Dis 1999;58:226-9 Cerca con Google

44. Gladman DD, Farewell VT. Progression in psoriatic arthritis: role of time varying clinical indicators. J Rheumatol 1999;26:2409-13. Cerca con Google

45. Punzi L, Podswiadek M, Oliviero F, Lonigro A, Modesti V, Ramonda R, Todesco S. Laboratory findings in psoriatic arthritis. Reumatismo 2007;59 Suppl 1:52-5. Cerca con Google

46. Gudjónsson JE, Kárason A, Antonsdóttir AA, Rúnarsdóttir EH, Gulcher JR, Stefánsson K, Valdimarsson H. HLA-Cw6-positive and HLA-Cw6-negative patients with Psoriasis vulgaris have distinct clinical features. J Invest Dermatol 2002;118:362-5. Cerca con Google

47. Rahman P, Elder JT. Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis 2005;64 Suppl 2:ii37-9; discussion ii40-1. Cerca con Google

48. O'Rielly DD, Rahman P. Genetics of psoriatic arthritis. Best Pract Res Clin Rheumatol 2014;28:673-85. Cerca con Google

49. Gladman DD, Helliwell PS, Mease PJ; Group for Reasearch and Assessment of Psoriasis and Psoriatic Arthritis. GRAPPA at the European League Against Rheumatism (EULAR) 2008. J Rheumatol 2009;36:656-8. Cerca con Google

50. Gossec L, Smolen JS, Ramiro S, de Wit M, Cutolo M, Dougados M, et al. European League Against Rheumatism (EULAR) recommendations for the management of psoriatic arthritis with pharmacological therapies: 2015 update. Ann Rheum Dis 2016;75:499-510. Cerca con Google

51. Gossec L, Smolen JS. Treatment of psoriatic arthritis: management recommendations. Clin Exp Rheumatol 2015;33:S73-7. Cerca con Google

52. Ramos M, López de Castro JA. HLA-B27 and the pathogenesis of spondyloarthritis. Tissue Antigens 2002;60:191-205. Cerca con Google

53. Chatzikyriakidou A, Voulgari PV, Drosos AA. What is the role of HLA-B27 in spondyloarthropathies? Autoimmun Rev 2011;10:464-8. Cerca con Google

54. Benjamin R, Parham P. Guilt by association: HLA-B27 and ankylosing spondylitis. Immunol Today 1990;11:137-42. Cerca con Google

55. Atagunduz P, Appel H, Kuon W, Wu P, Thiel A, Kloetzel PM, Sieper J. HLA-B27-restricted CD8+ T cell response to cartilage-derived self peptides in ankylosing spondylitis. Arthritis Rheum 2005;52:892-901. Cerca con Google

56. López de Castro JA. HLA-B27 and the pathogenesis of spondyloarthropathies. Immunol Lett 2007;108:27-33. Cerca con Google

57. Breban M, Fernández-Sueiro JL, Richardson JA, Hadavand RR, Maika SD, Hammer RE, Taurog JD. T cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats. J Immunol 1996;156:794-803. Cerca con Google

58. May E, Dorris ML, Satumtira N, Iqbal I, Rehman MI, Lightfoot E, Taurog JD. CD8 alpha beta T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats. J Immunol 2003;170:1099-105. Cerca con Google

59. Schröder M, Kaufman RJ. ER stress and the unfolded protein response. Mutat Res 2005;569:29-63. Cerca con Google

60. Colbert RA. HLA-B27 misfolding: a solution to the spondyloarthropathy conundrum? Mol Med Today 2000;6:224-30. Cerca con Google

61. Turner MJ, Sowders DP, DeLay ML, Mohapatra R, Bai S, Smith JA, et al. HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response. J Immunol 2005;175:2438-48. Cerca con Google

62. Tran TM, Dorris ML, Satumtira N, Richardson JA, Hammer RE, Shang J, Taurog JD. Additional human beta2-microglobulin curbs HLA-B27 misfolding and promotes arthritis and spondylitis without colitis in male HLA-B27-transgenic rats. Arthritis Rheum 2006;54:1317-27. Cerca con Google

63. Bird LA, Peh CA, Kollnberger S, Elliott T, McMichael AJ, Bowness P. Lymphoblastoid cells express HLA-B27 homodimers both intracellularly and at the cell surface following endosomal recycling. Eur J Immunol 2003;33:748-59. Cerca con Google

64. Kollnberger S, Bird L, Sun MY, Retiere C, Braud VM, McMichael A, Bowness P. Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthritis Rheum 2002;46:2972-82. Cerca con Google

65. Chan AT, Kollnberger SD, Wedderburn LR, Bowness P. Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis. Arthritis Rheum 2005;52:3586-95. Cerca con Google

66. Van Kuijk AW, Reinders-Blankert P, Smeets TJ, Dijkmans BA, Tak PP. Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment. Ann Rheum Dis 2006;65:1551-7. Cerca con Google

67. Bal A, Unlu E, Bahar G, Aydog E, Eksioglu E, Yorgancioglu R. Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol 2007;26:211-5. Cerca con Google

68. Rudwaleit M, Siegert S, Yin Z, Eick J, Thiel A, Radbruch A, et al. Low T cell production of TNFalpha and IFNgamma in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism. Ann Rheum Dis 2001;60:36-42. Cerca con Google

69. Verweij CL. Tumour necrosis factor gene polymorphisms as severity markers in rheumatoid arthritis. Ann Rheum Dis 1999;58 Suppl 1:I20-6. Cerca con Google

70. El-Tahan RR, Ghoneim AM, El-Mashad N. TNF-α gene polymorphisms and expression. Springerplus 2016;5:1508. Cerca con Google

71. Chung WT, Choe JY, Jang WC, Park SM, Ahn YC, Yoon IK, et al. Polymorphisms of tumor necrosis factor-α promoter region for susceptibility to HLA-B27-positive ankylosing spondylitis in Korean population. Rheumatol Int 2011;31:1167-75. Cerca con Google

72. Li B, Wang P, Li H. The association between TNF-alpha promoter polymorphisms and ankylosing spondylitis: a meta-analysis. Clin Rheumatol 2010;29:983-90. Cerca con Google

73. Lee YH, Song GG. Lack of association of TNF-alpha promoter polymorphisms with ankylosing spondylitis: a meta-analysis. Rheumatology 2009;48:1359-62. Cerca con Google

74. Poddubnyy DA, Märker-Hermann E, Kaluza-Schilling W, Zeidler H, Braun J, Listing J, et al. Relation of HLA-B27, tumor necrosis factor-α promoter gene polymorphisms, and T cell cytokine production in ankylosing spondylitis -- a comprehensive genotype-phenotype analysis from an observational cohort. J Rheumatol 2011;38:2436-41. Cerca con Google

75. Vargas-Alarcón G, Casasola-Vargas J, Rodríguez-Pérez JM, Huerta-Sil G, Pérez-Hernández N, Londoño J, et al. Tumor necrosis factor-alpha promoter polymorphisms in Mexican patients with spondyloarthritis. Hum Immunol 2006;67:826-32. Cerca con Google

76. Shiau MY, Lo MK, Chang CP, Yang TP, Ho KT, Chang YH. Association of tumour necrosis factor alpha promoter polymorphisms with ankylosing spondylitis in Taiwan. Ann Rheum Dis 2007;66:562-3. Cerca con Google

77. Nossent JC, Sagen-Johnsen S, Bakland G. Tumor necrosis factor-α promoter -308/238 polymorphism association with less severe disease in ankylosing spondylitis is unrelated to serum TNF-α and does not predict TNF inhibitor response. J Rheumatol 2014;41:1675-82. Cerca con Google

78. Manolova I, Ivanova M, Stoilov R, Rashkov R, Stanilova S. Association of single nucleotide polymorphism at position -308 of the tumor necrosis factor-alpha gene with ankylosing spondylitis and rheumatoid arthritis. Biotechnol Biotechnol Equip 2014;28:1108-1114. Cerca con Google

79. Höhler T, Grossmann S, Stradmann-Bellinghausen B, Kaluza W, Reuss E, de Vlam K, et al. Differential association of polymorphisms in the TNFalpha region with psoriatic arthritis but not psoriasis. Ann Rheum Dis 2002;61:213-8. Cerca con Google

80. Höhler T, Schäper T, Schneider PM, Meyer zum Büschenfelde KH, Märker-Hermann E. Association of different tumor necrosis factor alpha promoter allele frequencies with ankylosing spondylitis in HLA-B27 positive individuals. Arthritis Rheum 1998;41:1489-92. Cerca con Google

81. Milicic A, Lindheimer F, Laval S, Rudwaleit M, Ackerman H, Wordsworth P, et al. Interethnic studies of TNF polymorphisms confirm the likely presence of a second MHC susceptibility locus in ankylosing spondylitis. Genes Immun 2000;1:418-22. Cerca con Google

82. McGarry F, Walker R, Sturrock R, Field M. The -308.1 polymorphism in the promoter region of the tumor necrosis factor gene is associated with ankylosing spondylitis independent of HLA-B27. J Rheumatol 1999;26:1110-6. Cerca con Google

83. Fraile A, Nieto A, Beraún Y, Vinasco J, Matarán L, Martín J. Tumor necrosis factor gene polymorphisms in ankylosing spondylitis. Tissue Antigens 1998;51:386-90. Cerca con Google

84. Kaijzel EL, Brinkman BM, van Krugten MV, Smith L, Huizinga TW, et al. Polymorphism within the tumor necrosis factor alpha (TNF) promoter region in patients with ankylosing spondylitis. Hum Immunol 1999;60:140-4. Cerca con Google

85. Gallo E, Cabaleiro T, Román M, Abad-Santos F, Daudén E. Study of genetic polymorphisms in the tumor necrosis factor α promoter region in Spanish patients with psoriasis. Actas Dermosifiliogr 2012;103:301-7. Cerca con Google

86. Giardina E, Hüffmeier U, Ravindran J, Behrens F, Lepre T, McHugh NJ, et al. Tumor necrosis factor promoter polymorphism TNF*-857 is a risk allele for psoriatic arthritis independent of the PSORS1 locus. Arthritis Rheum 2011;63:3801-6. Cerca con Google

87. Lv K, Chen R, Cai Q, Fang M, Sun S. Effects of a single nucleotide polymorphism on the expression of human tumor necrosis factor-alpha. Scand J Immunol 2006;64:164-9. Cerca con Google

88. Australo-Anglo-American Spondyloarthritis Consortium (TASC), Reveille JD, Sims AM, Danoy P, Evans DM, Leo P, Pointon et al. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet 2010;42:123-7. Cerca con Google

89. Brown MA. Genetics of ankylosing spondylitis. Curr Opin Rheumatol 2010;22:126-32. Cerca con Google

90. Costantino F, Talpin A, Evnouchidou I, Kadi A, Leboime A, Said-Nahal R, et al. ERAP1 Gene Expression Is Influenced by Nonsynonymous Polymorphisms Associated With Predisposition to Spondyloarthritis. Arthritis Rheumatol 2015;67:1525-34. Cerca con Google

91. Daryabor G, Mahmoudi M, Jamshidi A, Nourijelyani K, Amirzargar A, Ahmadzadeh N, et al. Determination of IL-23 receptor gene polymorphism in Iranian patients with ankylosing spondylitis. Eur Cytokine Netw 2014;25:24-9. Cerca con Google

92. Karaderi T, Keidel SM, Pointon JJ, Appleton LH, Brown MA, Evans DM, Wordsworth BP. Ankylosing spondylitis is associated with the anthrax toxin receptor 2 gene (ANTXR2). Ann Rheum Dis 2014;73:2054-8. Cerca con Google

93. Ma X, Liu Y, Zhang H, Qiu R, Zhao H, Xin Q, et al. Evidence for genetic association of CARD9 and SNAPC4 with ankylosing spondylitis in a Chinese Han population. J Rheumatol 2014;41:318-24. Cerca con Google

94. Jordan CT, Cao L, Roberson ED, Pierson KC, Yang CF, Joyce CE, et al. PSORS2 is due to mutations in CARD14. Am J Hum Genet 2012;90:784-95. Cerca con Google

95. Zinovieva E, Bourgain C, Kadi A, Letourneur F, Izac B, Said-Nahal R, et al. Comprehensive linkage and association analyses identify haplotype, near to the TNFSF15 gene, significantly associated with spondyloarthritis. PLoS Genet 2009;5:e1000528. Cerca con Google

96. Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D, et al. Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease. Hum Mol Genet 2005;14:3499-506. Cerca con Google

97. Takedatsu H, Michelsen KS, Wei B, Landers CJ, Thomas LS, Dhall D, et al. TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology 2008;135:552-67. Cerca con Google

98. Pointon JJ, Harvey D, Karaderi T, Appleton LH, Farrar C, Stone MA, et al. The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD). Ann Rheum Dis 2010;69:1243-6. Cerca con Google

99. Chadwick W, Magnus T, Martin B, Keselman A, Mattson MP, Maudsley S. Targeting TNF-alpha receptors for neurotherapeutics. Trends Neurosci 2008 ;31:504-11. Cerca con Google

100. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003;10:45-65. Cerca con Google

101. Van Hauwermeiren F, Vandenbroucke RE, Libert C. Treatment of TNF mediated diseases by selective inhibition of soluble TNF or TNFR1. Cytokine Growth Factor Rev 2011;22:311-9. Cerca con Google

102. Karaderi T, Pointon JJ, Wordsworth TW, Harvey D, Appleton LH, Cohen CJ, et al; Australo-Anglo-American Spondyloarthritis Consortium. Evidence of genetic association between TNFRSF1A encoding the p55 tumour necrosis factor receptor, and ankylosing spondylitis in UK Caucasians. Clin Exp Rheumatol 2012;30:110-3. Cerca con Google

103. Davidson SI, Liu Y, Danoy PA, Wu X, Thomas GP, Jiang L, et al; Australo-Anglo-American Spondyloarthritis Consortium., Visscher PM, Brown MA, Xu H. Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese. Ann Rheum Dis 2011;70:289-92. Cerca con Google

104. Yousaf N, Gould DJ, Aganna E, Hammond L, Mirakian RM, Turner MD, et al. Tumor necrosis factor receptor I from patients with tumor necrosis factor receptor-associated periodic syndrome interacts with wild-type tumor necrosis factor receptor I and induces ligand-independent NF-kappaB activation. Arthritis Rheum 2005;52:2906-16. Cerca con Google

105. Lehmann P, Salzberger B, Haerle P, Aksentijevich I, Kastner D, Schoelmerich J, et al. Variable intrafamilial expressivity of the rare tumor necrosis factor-receptor associated periodic syndrome-associated mutation I170N that affects the TNFR1A cleavage site. Mod Rheumatol 2010;20:311-5. Cerca con Google

106. Lobito AA, Gabriel TL, Medema JP, Kimberley FC. Disease causing mutations in the TNF and TNFR superfamilies: Focus on molecular mechanisms driving disease. Trends Mol Med 2011;17:494-505. Cerca con Google

107. Aganna E, Hammond L, Hawkins PN, Aldea A, McKee SA, van Amstel HK, et al. Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypes. Arthritis Rheum 2003;48:2632-44. Cerca con Google

108. Turner MD, Chaudhry A, Nedjai B. Tumour necrosis factor receptor trafficking dysfunction opens the TRAPS door to pro-inflammatory cytokine secretion. Biosci Rep 2012;32:105-12. Cerca con Google

109. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003;10:45-65. Cerca con Google

110. McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 1999;97:133-44. Cerca con Google

111. Stojanov S, McDermott MF. The tumour necrosis factor receptor-associated periodic syndrome: current concepts. Expert Rev Mol Med 2005;7:1-18. Cerca con Google

112. Milhavet F, Cuisset L, Hoffman HM, Slim R, El-Shanti H, Aksentijevich I, et al. The infevers autoinflammatory mutation online registry: update with new genes and functions. Hum Mutat 2008;29:803-8. Cerca con Google

113. Goris A, Fockaert N, Cosemans L, Clysters K, Nagels G, Boonen S, et al. TNFRSF1A coding variants in multiple sclerosis. J Neuroimmunol 2011;235:110-2. Cerca con Google

114. Rigante D, Cantarini L, Imazio M, Lucherini OM, Sacco E, Galeazzi M, et al. Autoinflammatory diseases and cardiovascular manifestations. Ann Med 2011;43:341-6. Cerca con Google

115. Van Hauwermeiren F, Vandenbroucke RE, Libert C. Treatment of TNF mediated diseases by selective inhibition of soluble TNF or TNFR1. Cytokine Growth Factor Rev 2011;22:311-9. Cerca con Google

116. Amigues I, Stojanovic KS, Bansal A, Gagnard A, Tebib JG. Ankylosing spondylitis associated with auto-inflammatory syndrome mutation. Joint Bone Spine 2011;78:530-1. Cerca con Google

117. French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997;17:25-31. Cerca con Google

118. Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 2009;27:621-68. Cerca con Google

119. Touitou I. The spectrum of Familial Mediterranean Fever (FMF) mutations. Eur J Hum Genet 2001;9:473-83. Cerca con Google

120. Marek-Yagel D, Bar-Joseph I, Pras E, Berkun Y. Is E148Q a benign polymorphism or a disease-causing mutation? J Rheumatol 2009;36:2372. Cerca con Google

121. Ozkurede VU, Franchi L. Immunology in clinic review series; focus on autoinflammatory diseases: role of inflammasomes in autoinflammatory syndromes. Clin Exp Immunol 2012;167:382-90. Cerca con Google

122. Heller H, Gafni J, Michaeli D, Shahin N, Sohar E, Ehrlich G, et al. The arthritis of familial Mediterranean fever (FMF). Arthritis Rheum 1966;9:1-17. Cerca con Google

123. Garcia-Gonzalez A, Weisman MH. The arthritis of familial Mediterranean fever. Semin Arthritis Rheum 1992;22:139-50. Cerca con Google

124. Akar S, Soysal O, Balci A, Solmaz D, Gerdan V, Onen F, et al. High prevalence of spondyloarthritis and ankylosing spondylitis among familial Mediterranean fever patients and their first-degree relatives: further evidence for the connection. Arthritis Res Ther 2013 28;15:R21. Cerca con Google

125. Maraş Y, Akdoğan A, Kisacik B, Kiliç L, Yilmaz E, Tufan A, et al. MEFV mutation frequency and effect on disease severity in ankylosing spondylitis. Turk J Med Sci 2014;44:203-7. Cerca con Google

126. Akkoc N, Gul A. Familial Mediterranean fever and seronegative arthritis. Curr Rheumatol Rep 2011;13:388-94. Cerca con Google

127. Yigit S, Inanir A, Karakus N, Kesici E, Bozkurt N. Common Mediterranean fever (MEFV) gene mutations associated with ankylosing spondylitis in Turkish population. Dis Markers 2012;33:113-8. Cerca con Google

128. Cosan F, Ustek D, Oku B, Duymaz-Tozkir J, Cakiris A, Abaci N, et al. Association of familial Mediterranean fever-related MEFV variations with ankylosing spondylitis. Arthritis Rheum 2010;62:3232-6. Cerca con Google

129. Durmus D, Alayli G, Cengiz K, Yigit S, Canturk F, Bagci H. Clinical significance of MEFV mutations in ankylosing spondylitis. Joint Bone Spine 2009;76:260-4. Cerca con Google

130. Cinar M, Dinc A, Simsek I, Erdem H, Koc B, Pay S, et al. The rate and significance of Mediterranean fever gene mutations in patients with ankylosing spondylitis: a three-month, longitudinal clinical study. Rheumatol Int 2008;29:37-42. Cerca con Google

131. Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther 2008;117:244-79. Cerca con Google

132. Horiuchi T, Mitoma H, Harashima S, Tsukamoto H, Shimoda T. Transmembrane TNF-alpha: structure, function and interaction with anti-TNF agents. Rheumatology 2010;49:1215-28. Cerca con Google

133. Scallon B, Cai A, Solowski N, Rosenberg A, Song XY, Shealy D, Wagner C. Binding and functional comparisons of two types of tumor necrosis factor antagonists. J Pharmacol Exp Ther 2002;301:418-26. Cerca con Google

134. Braun J, Brandt J, Listing J, Rudwaleit M, Sieper J. Biologic therapies in the spondyloarthritis: new opportunities, new challenges. Curr Opin Rheumatol 2003;15:394-407. Cerca con Google

135. Maneiro JR, Souto A, Salgado E, Mera A, Gomez-Reino JJ. Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis. RMD Open 2015 18;1:e000017. Cerca con Google

136. Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis 2004;63:665-70. Cerca con Google

137. Vastesaeger N, van der Heijde D, Inman RD, Wang Y, Deodhar A, Hsu B, et al. Cerca con Google

Predicting the outcome of ankylosing spondylitis therapy. Ann Rheum Dis 2011;70:973-81. Cerca con Google

138. Rudwaleit M, Claudepierre P, Wordsworth P, Cortina EL, Sieper J, Kron M, et al. Effectiveness, safety, and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis. J Rheumatol 2009;36:801-8. Cerca con Google

139. Song GG, Seo YH, Kim JH, Choi SJ, Ji JD, Lee YH. Association between TNF-α (-308 A/G, -238 A/G, -857 C/T) polymorphisms and responsiveness to TNF-α blockers in spondyloarthropathy, psoriasis and Crohn's disease: a meta-analysis. Cerca con Google

Pharmacogenomics 2015;16:1427-37. Cerca con Google

140. Liu J, Dong Z, Zhu Q, He D, Ma Y, Du A, et al. TNF-α Promoter Polymorphisms Predict the Response to Etanercept More Powerfully than that to Infliximab/Adalimumab in Spondyloarthritis. Sci Rep 2016;6:32202. Cerca con Google

141. Pierik M, Vermeire S, Steen KV, Joossens S, Claessens G, Vlietinck R, Rutgeerts P. Tumour necrosis factor-alpha receptor 1 and 2 polymorphisms in inflammatory bowel disease and their association with response to infliximab. Aliment Pharmacol Ther 2004;20:303-10. Cerca con Google

142. Matsukura H, Ikeda S, Yoshimura N, Takazoe M, Muramatsu M. Genetic polymorphisms of tumour necrosis factor receptor superfamily 1A and 1B affect responses to infliximab in Japanese patients with Crohn's disease. Aliment Pharmacol Ther 2008;27:765-70. Cerca con Google

143. Schiotis R, Sánchez A, Escudero A, Bartolomé N, Szczypiorska M, Font P, et al. Candidate's single-nucleotide polymorphism predictors of treatment nonresponse to the first anti-TNF inhibitor in ankylosing spondylitis. Rheumatol Int 2014;34:793-801. Cerca con Google

144. Marchenko YV, Carroll RJ, Lin DY, Amos CI, Gutierrez RG. Semiparametric analysis of case–control genetic data in the presence of environmental factors. Stata Journal Volume 8 Number 3; 2008. Cerca con Google

145. Coates LC, FitzGerald O, Helliwell PS, Paul C. Psoriasis, psoriatic arthritis, and rheumatoid arthritis: Is all inflammation the same? Semin Arthritis Rheum 2016. pii: S0049-0172:30064-6. Cerca con Google

146. Miele L, Vallone S, Cefalo C, La Torre G, Di Stasi C, Vecchio FM, et al. Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol 2009;51:778-86. Cerca con Google

147. Elahi MM, Asotra K, Matata BM, Mastana SS. Tumor necrosis factor alpha -308gene locus promoter polymorphism: an analysis of association with health and disease. Biochim Biophys Acta 2009;1792:163-72 Cerca con Google

148. Skoog T, van't Hooft FM, Kallin B, Jovinge S, Boquist S, Nilsson J, et al. A common functional polymorphism (C>A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum Mol Genet 1999;8:1443-9. Cerca con Google

149. Plasencia C, Pascual-Salcedo D, Nuño L, Bonilla G, Villalba A, Peiteado D, et al. Influence of immunogenicity on the efficacy of long term treatment of spondyloarthritis with infliximab. Ann Rheum Dis 2012;71:1955-60. Cerca con Google

150. McLeod C, Bagust A, Boland A, Dagenais P, Dickson R, Dundar Y, et al. Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation. Health Technol Assess 2007;11:1-158, iii-iv. Cerca con Google

151. Rossi E, Basso D, Zambon CF, Navaglia F, Greco E, Pelloso M, et al. TNFA Haplotype Genetic Testing Improves HLA in Estimating the Risk of Celiac Disease in Children. PLoS One 2015;10:e0123244. Cerca con Google

152. Ottoboni L, Frohlich IY, Lee M, Healy BC, Keenan BT, Xia Z, et al. Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus. Neurology 2013;81:1891-9. Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record