The role of socioeconomic status in the susceptibility to develop systemic lupus erythematosus in Mexican patients



Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well-identified as risk factors. SLE patients have different phenotypes or clinical presentations, which vary among Mexicans. This variation could be explained by ethnicity and admixture. Since socioeconomic status probably limits and change the patterns of migration, this factor could favor inbreeding and homogamy in some geographic areas. Consequently, it could alter or restrict the possibilities of admixture too. Therefore, the socioeconomic status may also have implications in the susceptibility and the clinical heterogeneity of SLE in Mexican patients.


One hundred twenty-three SLE patients and 234 healthy individuals with Mexican admixed ancestry were recruited. HLA alleles were analyzed using the HLA typing method based on Sequence-based typing (SBT).


As expected, it was found an increased frequency of the HLA-DRB1*03:01 allele in all socioeconomic groups when compared with healthy individuals. The susceptibility allele found in the low-income SLE patients was HLA-DRB1*04:05 whereas, the susceptibility alleles for the high-income SLE patients were HLA-DRB1*07:01 (pC = 0.03, OR = 2.0) and HLA-DRB1*11:04 (pC = 0.0004, OR = 5.1). Additionally, the frequencies of two protective alleles HLA-DRB1*14:06 (pC = 0.01, OR = 0.28) and HLA-DRB1*16:02 (pC = 0.04, OR = 0.22) were found diminished. These findings correlate with the admixture differences between low-income and high-income SLE patients. The clinical manifestations showed a different distribution between both groups. Arthritis and neurological disorder were prevalent in low-income SLE patients, while the hematological disorder was prevalent in high-income SLE patients.


These findings suggest that HLA class II DRB1 genes contribute to the susceptibility and protection to develop SLE differently depending on socioeconomic status. Due to this, the clinical manifestations vary among patients and it could be related to different admixture charge.

Key Point
HLA class II DRB1 genes contribute to the susceptibility and protection to develop SLE differently depending on socioeconomic status.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

    Ghodke-Puranik Y, Niewold TB (2015) Immunogenetics of systemic lupus erythematosus: a comprehensive review. J Autoimmun 64:125–136.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Valencia-Flores M, Reséndiz MC, Santiago V, Castaño V, Granados J, Camarena A et al (2010) Sleep, fatigue, depression, and pain in Mexican women with systemic lupus erythematosus: an exploratory study. Hisp Heal Care Int 8(4):217–226.

    Article  Google Scholar 

  3. 3.

    Carter EE, Barr SG, Clarke AE (2016) The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol 12(10):605–620.

    Article  PubMed  Google Scholar 

  4. 4.

    Tsokos GC, Lo MS, Reis PC, Sullivan KE (2016) New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol 12(12):716–730.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Walid W, Noor Eldeen E, Essam HM, Adel A, Khaled DH, Hamad AA et al (2014) Relation between HLA typing and clinical presentations in systemic lupus erythematosus patients in Al-Qassim region, Saudi Arabia. Int J Health Sci (Qassim) 8(2):159–165

    Article  Google Scholar 

  6. 6.

    Vasconcelos C, Carvalho C, Pereira C, Bettencourt A, Costa PP, Barbosa P et al (2009) HLA in Portuguese systemic lupus erythematosus patients and their relation to clinical features. Ann N Y Acad Sci 580:575–580.

    CAS  Article  Google Scholar 

  7. 7.

    Granados J, Zúñiga J, Acuña-Alonzo V, Rosetti F, Vargas-Alarcón G (2006) Influencia de alelos y haplotipos del complejo principal de histocompatibilidad en la susceptibilidad a lupus eritematoso generalizado en la población mexicana. Gac Med Mex 142(3):195–199

    PubMed  Google Scholar 

  8. 8.

    Furukawa H, Kawasaki A, Oka S, Ito I, Shimada K, Sugii S, Hashimoto A, Komiya A, Fukui N, Kondo Y, Ito S, Hayashi T, Matsumoto I, Kusaoi M, Amano H, Nagai T, Hirohata S, Setoguchi K, Kono H, Okamoto A, Chiba N, Suematsu E, Katayama M, Migita K, Suda A, Ohno S, Hashimoto H, Takasaki Y, Sumida T, Nagaoka S, Tsuchiya N, Tohma S (2014) Human leukocyte antigens and systemic lupus erythematosus: a protective role for the HLA-DR6 alleles DRB1*13:02 and *14:03. PLoS One 9(2):1–7.

    CAS  Article  Google Scholar 

  9. 9.

    Kim K, Bang SY, Lee HS, Okada Y, Han B, Saw WY, Teo YY, Bae SC (2014) The HLA-DRβ1 amino acid positions 11-13-26 explain the majority of SLE-MHC associations. Nat Commun 5:5902.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Ceccarelli F, Perricone C, Borgiani P, Ciccacci C, Rufini S, Cipriano E et al (2015) Genetic factors in systemic lupus erythematosus: contribution to disease phenotype. J Immunol Res 2015:1–11.

    CAS  Article  Google Scholar 

  11. 11.

    Pons-Estel BA, Catoggio LJ, Cardiel MH, Soriano ER, Gentiletti S, Villa AR, Abadi I, Caeiro F, Alvarellos A, Alarcón-Segovia D, Grupo Latinoamericano de Estudio del Lupus (2004) The GLADEL multinational Latin American prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among “Hispanics”. Medicine. 83(1):1–17.

    Article  PubMed  Google Scholar 

  12. 12.

    Moreno-Estrada A, Gignoux CR, Fernandez-Lopez JC, Zakharia F, Sikora M, Contreras AV et al (2014) The genetics of Mexico recapitulates Native American substructure and affects biomedical traits. Science 344(6189):1280–1285.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Mizuno F, Gojobori J, Wang L, Onishi K, Sugiyama S, Granados J, Gomez-Trejo C, Acuña-Alonzo V, Ueda S (2014) Complete mitogenome analysis of indigenous populations in Mexico: its relevance for the origin of Mesoamericans. J Hum Genet 59(7):359–367.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Hochberg MC (1997) Updating the American college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725–1734.<1725::AID-ART29>3.0.CO;2-Y

    CAS  Article  Google Scholar 

  15. 15.

    Guzman J, Cardiel MH, Arce-Salinas A, Sanchez-Guerrero J, Alarcón-Segovia D (1992) Measurement of disease activity in systemic lupus erythematosus. Prospective validation of 3 clinical indices. J Rheumatol 19(10):1551–1558

    CAS  PubMed  Google Scholar 

  16. 16.

    Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35(6):630–640

    CAS  Article  Google Scholar 

  17. 17.

    Zúñiga J, Yu N, Barquera R, Alosco S, Ohashi M, Lebedeva T, Acuña-Alonzo V, Yunis M, Granados-Montiel J, Cruz-Lagunas A, Vargas-Alarcón G, Rodríguez-Reyna TS, Fernandez-Viña M, Granados J, Yunis EJ (2013) HLA class I and class II conserved extended haplotypes and their fragments or blocks in Mexicans: implications for the study of genetic diversity in admixed populations. PLoS One 8(9).

  18. 18.

    Robinson J, Malik A, Parham P, Bodmer JG, Marsh SGE (2001) IMGT/HLA database-a sequence database for the human major histocompatibility complex. Nucleic Acids Res 29(1):210–213

  19. 19.

    Lebedeva TV, Mastromarino SA, Lee E, Ohashi M, Alosco SM, Yu N (2011) Resolution of HLA class I sequence-based typing ambiguities by group-specific sequencing primers. Tissue Antigens 77(3):247–250.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Wang J (2003) Maximum-likelihood estimation of admixture proportions from genetic data. Genetics. 164:747–765

    PubMed  PubMed Central  Google Scholar 

  21. 21.

    Rodriguez-sanchez J (2002) Molecular analysis of HLA-DRB1 polymorphism in north-east Spain. Eur J Immunogenet 29:75–77.

    Article  PubMed  Google Scholar 

  22. 22.

    Paximadis M, Mathebula TY, Gentle NL, Vardas E, Colvin M, Gray CM, Tiemessen CT, Puren A (2012) Human leukocyte antigen class I (A,B,C) and II (DRB1) diversity in the black and Caucasian South African population. Hum Immunol 73(1):80–92.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Arnaiz-villena A, Vargas-alarco G, Areces C, Enrı M, Abd-el-fatah-khalil S, Ferna M et al (2014) Mixtec Mexican Amerindians : an HLA alleles study for America peopling, pharmacogenomics, and transplantation. Immunol Investig 43(8):738–755.

    CAS  Article  Google Scholar 

  24. 24.

    García-Ortíz J, Sandoval-Ramírez L, Rangel-Villalobos H, Maldonado-Torres H, Cox S, García-Sepúlveda C et al (2006) High-resolution molecular characterization of the HLA class I and class II in the Tarahumara Amerindian population. Tissue Antigens 68(5):135–146.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Ikeda N, Kojima H, Nishikawa M, Hayashi K, Futagami T, Tsujino T, Kusunoki Y, Fujii N, Suegami S, Miyazaki Y, Middleton D, Tanaka H, Saji H (2015) Determination of HLA-A, -C, -B, -DRB1 allele and haplotype frequency in Japanese population based on family study. Tissue Antigens 85:252–259.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Gutierrez-Arcelus M, Rich SS, Raychaudhuri S (2016) Autoimmune diseases connecting risk alleles with molecular traits of the immune system. Nat Rev Genet 17(3):160–174.

    Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Repeinertsen JL, Klippel JH, Jonhson AH, Steinberg AD, Decker JL, Mann DL (1978) B-lymphocyte alloantigens associated with systemic lupus erythematous. N Engl J Med 299(10).

  28. 28.

    Vargas-Alarcón G, Salgado N, Granados J, Gómez-Casado E, Martinez-Laso J, Alcocer-Varela J, Arnaiz-Villena A, Alarcón-Segovia D (2001) Class II allele and haplotype frequencies in Mexican systemic lupus erythematosus patients: the relevance of considering homologous chromosomes in determining susceptibility. Hum Immunol 62(8):814–820.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Bekker-Mendez C, Yamamoto-Furusho JK, Vargas-Alarcon G, Ize-Ludlow D, Alcocer-Varela J, Granados J (1998) Haplotype distribution of class II MHC genes in Mexican patients with systemic lupus erythematosus. Scand J Rheumatol 27(5):373–376

    CAS  Article  Google Scholar 

  30. 30.

    Granados J, Vargas-Alarcón G, Andrade F, Melin-Aldana et al (1996) The role of HLA-DR alleles and complotypes through the ethnic barrier in systemic lupus erythematosus in Mexicans. Lupus. 5:184–189.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Penaranda-Parada E, Quintana G, Yunis JJ, Mantilla R, Rojas W, Panqueva U et al (2015) Clinical, serologic, and immunogenetic characterization (HLA-DRB1) of late-onset lupus erythematosus in a Colombian population. Lupus. 24(12):1293–1299.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Graham RR, Ortmann W, Rodine P, Espe K, Langefeld C, Lange E, Williams A, Beck S, Kyogoku C, Moser K, Gaffney P, Gregersen PK, Criswell LA, Harley JB, Behrens TW (2007) Specific combinations of HLA-DR2 and DR3 class II haplotypes contribute graded risk for disease susceptibility and autoantibodies in human SLE. Eur J Hum Genet 15:823–830

    CAS  Article  Google Scholar 

  33. 33.

    Hashimoto H, Nishimura Y, Dong RP, Kimura A, Sasazuki T, Vamanakal K et al (1994) HLA antigens in Japanese patients with systemic lupus erythematosus. Rheumatology. 23(4):191–196

    CAS  Google Scholar 

  34. 34.

    Suggs MJL, Majithia V, Lewis RE, Cruse JM (2011) HLA DRB1*15:03 allelic haplotype predominance and associated immunodysregulation in systemic lupus erythematosus. Exp Mol Pathol. 91:548–562.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Niu Z, Zhang P, Tong Y (2015) Value of HLA-DR genotype in systemic lupus erythematosus and lupus nephritis: a meta-analysis. Int J Rheum Dis 18(1):17–28.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Granados J, Vargas-Alarcón G, Drenkard C, Andrade F, Melín-Aldana H, Alcocer-Varela J, Alarcón-Segovia D (1997) Relationship of anticardiolipin antibodies and antiphospholipid syndrome to HLA-DR7 in Mexican patients with systemic lupus erythematosus (SLE). Lupus. 6(1):57–62

    CAS  Article  Google Scholar 

  37. 37.

    Trabace S, Nicotra M, Cappellacci S, Morellini M, Muttinelli C, Anna M et al (1991) HLA-DR and DQ antigens and anticardiolipin antibodies in women with recurrent spontaneous abortions. Am J Reprod Immunol 26:147–149

    CAS  Article  Google Scholar 

  38. 38.

    Panzer S, Pabinger I, Gschwandtner ME, Mayr WR, Hutter D (1997) Lupus anticoagulants : strong association with the major histocompatibility complex class II and platelet antibodies. Br J Haematol 98:342–345

    CAS  Article  Google Scholar 

  39. 39.

    Camps MT, Cuadrado MJ, Ocón P, et al (1995) Association between HLA class II antigens and primary antiphospholipid syndrome from the south of Spain. Lupus 4(1):51–55.

  40. 40.

    González-Galarza FF, Takeshita LYC, Santos EJM, Kempson F, Thomaz Maia MH, Soares da Silva AL, Teles e Silva AL, Ghattaoraya GS, Alfirevic A, Jones A and Derek M (2015). Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Research. 43: 784–788, Allele Frequencies in Worldwide populations [Internet]. [Revised on April 2019]

Download references


The authors thank all individuals with SLE and healthy individuals who have participated in this genetic study.


This work was supported by grant no. 000 000 000273175 from the CONACYT (Consejo Nacional de Ciencia y Tecnología de México).

Author information



Corresponding author

Correspondence to Julio Granados.

Ethics declarations

The Ethics Committee from the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán reviewed and approved the protocol for this genetic study.



Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Salgado-Galicia, N.A., Hernández-Doño, S., Ruiz-Gómez, D. et al. The role of socioeconomic status in the susceptibility to develop systemic lupus erythematosus in Mexican patients. Clin Rheumatol 39, 2151–2161 (2020).

Download citation


  • High-income
  • HLA-DRB1 alleles
  • Low-income
  • Systemic lupus erythematosus