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Frequency of human leukocyte antigens class II-DR alleles (HLA-DRB1) in Argentinian patients with early arthritis

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Abstract

Patients with rheumatoid arthritis (RA) or undifferentiated arthritis (UA) in the CONAART database (Argentine Consortium for Early Arthritis) were assessed for genetic risk factors for RA, specifically for HLA-DRB1 alleles and the PTPN22 rs2476601 polymorphism associated with progression to RA. This is a case-control study. Blood samples were obtained to determine HLA-DRB1 genotypes by PCR-SSO Luminex and PTPN22 (rs2476601) polymorphism by allelic discrimination. A control group of individuals from the general Argentinian population were obtained from the national register of cadaveric organ donors. A total of 1859 individuals were included in this analysis: 399 patients from the CONAART database (347 patients with RA at study end and 52 patients with UA at study end, mean follow-up time 25 ± 18 months) and 1460 individuals from the general Argentinian population. Compared with the controls, the HLA-DRB1*04 and DRB1*09 alleles were more commonly detected in patients with RA diagnosis (OR (95% CI) 2.23 (1.74–2.85) and 1.89 (1.26–2.81)) respectively. Both patients with UA and the general population showed higher frequency of DRB1*07, DRB1*11 and DRB1*15 alleles than patients with RA. PTPN22 rs2476601 polymorphism frequency was higher in RA and UA vs the general population; however, this was significantly different only for RA vs control group (OR [95% CI] = 1.81 [1.10–3.02], P = 0.018. HLA-DRB1 typing and PTPN22 allelic discrimination could distinguish between patients with UA, patients with early RA, and the general population in Argentina. This is the first study of HLA-DRB1 alleles and PTPN22 polymorphism associations with progression to early RA in an Argentinian population.

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References

  1. Mochan E, Ebell MH (2008) Predicting rheumatoid arthritis risk in adults with undifferentiated arthritis. Am Fam Physician 77(10):1451–1453

    PubMed  Google Scholar 

  2. Brinkmann GH, Norli ES, Kvien TK, Haugen AJ, Grovle L, Nygaard H et al (2017) Disease characteristics and rheumatoid arthritis development in patients with early undifferentiated arthritis: a 2-year followup study. J Rheumatol 44(2):154–161

    Article  PubMed  Google Scholar 

  3. Verpoort KN, van Dongen H, Allaart CF, Toes RE, Breedveld FC, Huizinga TW (2004) Undifferentiated arthritis—disease course assessed in several inception cohorts. Clin Exp Rheumatol 22(5 Suppl 35):S12–S17

    PubMed  CAS  Google Scholar 

  4. Hazes JM, Luime JJ (2011) The epidemiology of early inflammatory arthritis. Nat Rev Rheumatol 7(7):381–390

    Article  PubMed  Google Scholar 

  5. Olivieri I, Sarzi-Puttini P, Bugatti S, Atzeni F, d’Angelo S, Caporali R (2012) Early treatment in early undifferentiated arthritis. Autoimmun Rev 11(8):589–592

    Article  PubMed  CAS  Google Scholar 

  6. Stastny P (1978) Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. N Engl J Med 298(16):869–871

    Article  PubMed  CAS  Google Scholar 

  7. Kampstra ASB, Toes REM (2017) HLA class II and rheumatoid arthritis: the bumpy road of revelation. Immunogenetics 69(8–9):597–603

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC et al (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75(2):330–337

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Citera G, Padulo LA, Fernandez G, Lazaro MA, Rosemffet MG, Maldonado Cocco JA (2001) Influence of HLA-DR alleles on rheumatoid arthritis: susceptibility and severity in Argentine patients. J Rheumatol 28(7):1486–1491

    PubMed  CAS  Google Scholar 

  10. Usnayo MJ, Andrade LE, Alarcon RT, Oliveira JC, Silva GM, Bendet I et al (2011) Study of the frequency of HLA-DRB1 alleles in Brazilian patients with rheumatoid arthritis. Rev Bras Reumatol 51(5):474–483

    Article  PubMed  Google Scholar 

  11. Barros Bértolo M, Lavras Costallat LT, Persoli LB, Ferreira CF (2001) HLA-DRB1 alleles and the prognosis of rheumatoid arthritis in Brazilian patients. Rev Bras Reumatol 41:151–156

    Google Scholar 

  12. Gonzalez A, Nicovani S, Massardo L, Aguirre V, Cervilla V, Lanchbury JS, Jacobelli S (1997) Influence of the HLA-DR beta shared epitope on susceptibility to and clinical expression of rheumatoid arthritis in Chilean patients. Ann Rheum Dis 56(3):191–193

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Anaya JM, Correa PA, Mantilla RD, Arcos-Burgos M (2002) Rheumatoid arthritis association in Colombian population is restricted to HLA-DRB1*04 QRRAA alleles. Genes Immun 3(1):56–58

    Article  PubMed  CAS  Google Scholar 

  14. Ruiz-Morales JA, Vargas-Alarcon G, Flores-Villanueva PO, Villarreal-Garza C, Hernandez-Pacheco G, Yamamoto-Furusho JK et al (2004) HLA-DRB1 alleles encoding the “shared epitope” are associated with susceptibility to developing rheumatoid arthritis whereas HLA-DRB1 alleles encoding an aspartic acid at position 70 of the beta-chain are protective in Mexican Mestizos. Hum Immunol 65(3):262–269

    Article  PubMed  CAS  Google Scholar 

  15. Debaz H, Olivo A, Vazquez Garcia MN, de la Rosa G, Hernandez A, Lino L, Burgos R, Fernandez-Viña M, Stastny P, Gorodezky C (1998) Relevant residues of DRbeta1 third hypervariable region contributing to the expression and to severity of rheumatoid arthritis (RA) in Mexicans. Hum Immunol 59(5):287–294

    Article  PubMed  CAS  Google Scholar 

  16. del Rincon I, Escalante A (1999) HLA-DRB1 alleles associated with susceptibility or resistance to rheumatoid arthritis, articular deformities, and disability in Mexican Americans. Arthritis Rheum 42(7):1329–1338

    Article  PubMed  Google Scholar 

  17. Castro F, Acevedo E, Ciusani E, Angulo JA, Wollheim FA, Sandberg-Wollheim M (2001) Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles in Peruvian patients with rheumatoid arthritis. Ann Rheum Dis 60(8):791–795

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Angulo J, Miraval T, Ponce de León H, Reveille J (2003) Epítope reumatoide y alelo HLA-DRB1⁎0404 se asocian con susceptibilidad para artritis reumatoide en mestizos peruanos. Rev Peru Reumatol 9:26–32

    Google Scholar 

  19. Mendoza Rincón JF, López Cano D, Jiménez Morales S, Rivas Jiménez ML, Barbosa Cobos RE, Ramírez BJ (2016) The functional PTPN22 C1858T polymorphism confers risk for rheumatoid arthritis in patients from Central Mexico. Clin Rheumatol 35(6):1457–1462

    Article  Google Scholar 

  20. Torres-Carrillo NM, Ruiz-Noa Y, Martinez-Bonilla GE, Leyva-Torres SD, Torres-Carrillo N, Palafox-Sanchez CA et al (2012) The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico. Immunol Lett 147(1–2):41–46

    Article  PubMed  CAS  Google Scholar 

  21. Ramirez M, Quintana G, Diaz-Gallo LM, Caminos J, Garces M, Cepeda L et al (2012) The PTPN22 C1858T variant as a risk factor for rheumatoid arthritis and systemic lupus erythematosus but not for systemic sclerosis in the Colombian population. Clin Exp Rheumatol 30(4):520–524

    PubMed  Google Scholar 

  22. Gomez LM, Anaya JM, Gonzalez CI, Pineda-Tamayo R, Otero W, Arango A, Martín J (2005 Oct) PTPN22 C1858T polymorphism in Colombian patients with autoimmune diseases. Genes Immun 6(7):628–631

    Article  PubMed  CAS  Google Scholar 

  23. Marcos J, Waimann C, Dal Pra F, Hogrefe J, Retamozo S, Caeiro F, Casalla L, Benegas M, Rillo O, Spindler A, Berman H, Berman A, Secco A, Garcia Salinas R, Catalan Pellet A, Ceccato F, Paira S, Marcos JC, Maldonado Cocco JA, Citera G, on behalf of CONAART (Consorcio Argentino de Artritis Temprana—Argentine Consortium for Early Arthritis) (2011) General characteristics of an early arthritis cohort in Argentina. Rheumatology (Oxford) 50(1):110–116

    Article  Google Scholar 

  24. Citera G, Arriola MS, Maldonado-Cocco JA, Rosemffet MG, Sanchez MM, Goni MA et al (2004) Validation and crosscultural adaptation of an argentine Spanish version of the health assessment questionnaire disability index. J Clin Rheumatol 10(3):110–115

    Article  PubMed  Google Scholar 

  25. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO III et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581

    Article  PubMed  Google Scholar 

  26. Delgado-Vega AM, Anaya JM (2007 Jun) Meta-analysis of HLA-DRB1 polymorphism in Latin American patients with rheumatoid arthritis. Autoimmun Rev 6(6):402–408

    Article  PubMed  CAS  Google Scholar 

  27. van der Heijde DM, van Riel PL, van Leeuwen MA, van’t Hof MA, van Rijswijk MH, van de Putte LB (1992) Prognostic factors for radiographic damage and physical disability in early rheumatoid arthritis. A prospective follow-up study of 147 patients. Br J Rheumatol 31(8):519–525

    Article  PubMed  Google Scholar 

  28. Padyukov L, Silva C, Stolt P, Alfredson L, Klareskog L (2004) A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum 50:3085–3092

    Article  PubMed  CAS  Google Scholar 

  29. Kallberg H, Padyukov L, Plenge RM, Rönnelid J, Gregersen PK, van der Helm-van Mil AH et al (2007) Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet 80:867–875

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

The authors wish to thank all patients who participated in this study; they also wish to thank all the colleagues who during their fellowship participated in the evaluation of patients in CONAART (Margarita Landi MD, Alejandro Cayetti MD, Ana Lizarraga MD, Federico Ceccato MD).

Funding

The work was sponsored by an unrestricted grant from Pfizer Argentina. Pfizer had interference neither in driving nor in the analysis or writing of the study.

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Correspondence to Gustavo Citera.

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Citera, G., Pra, F.D., Waimann, C.A. et al. Frequency of human leukocyte antigens class II-DR alleles (HLA-DRB1) in Argentinian patients with early arthritis. Clin Rheumatol 38, 675–681 (2019). https://doi.org/10.1007/s10067-018-4319-4

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