https://doi.org/10.4081/reumatismo.2023.1541
Clinical features and genetic biomarkers associated with different phenotypes of systemic lupus erythematosus in Paraguayan patients
Submitted: 6 December 2022
Accepted: 2 June 2023
Published: 17 July 2023
Accepted: 2 June 2023
Abstract Views: 479
PDF: 335
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by a heterogeneous clinical picture that makes the diagnosis and follow-up of these patients difficult. This study aimed to identify correlations between clinical, immunological, and genetic biomarkers and clinical manifestations in SLE. A retrospective study of data from medical records and immunological and genetic studies of SLE patients in Paraguay was carried out. A descriptive analysis was performed based on the type of variable. Human leukocyte antigen (HLA) allele frequencies (DPA1, DPB1, DQA1, DQB1, and DRB1) were calculated, and univariate logistic regression analyses were performed between each of the explanatory variables and the presence or absence of each phenotype. Odds ratios, 95% confidence intervals, and p values were recorded. Associations with p<0.05 were considered statistically significant. 104 SLE patients were included: 86% were female, with a mean age of 32.80±10.36 years. An association was identified between anti-double stranded DNA (anti-dsDNA) and the presence of the renal phenotype and between anti-dsDNA and the absence of the joint and hematological phenotypes. Immunoglobulin M isotype rheumatoid factor was associated with the absence of a renal phenotype. HLA-DQB1*02:02 and HLA-DRB1*07:01 were associated with the cutaneous phenotype. An association was identified between age at disease onset over 30 years and the presence of the joint phenotype. No other associations were identified. Potential clinical, immunological, and genetic biomarkers of phenotypes have been identified in SLE Paraguayan patients.
Peñaranda-Parada E, Quintana G, Yunis JJ, Mantilla R, Rojas W, Panqueva U, et al. Clinical, serologic, and immunogenetic characterization (HLA-DRB1) of late-onset lupus erythematosus in a colombian population. Lupus 2015; 24: 1293-9.
DOI: https://doi.org/10.1177/0961203315588576
Pons-Estel GJ, Catoggio LJ, Cardiel MH, Bonfa E, Caeiro F, Sato E et al. Lupus in latin-american patients: lessos from the GLADEL cohorte. Lupus 2015; 24: 536-45.
DOI: https://doi.org/10.1177/0961203314567753
Cervera R, Khamashta MA, Font J, Sebastini GD, Gil A, Lavilla P, et al. Systemic lupus erythematosis: clinical and inmmunologic patterns of disease expression in a cohort of 1000 patients. the european working partyon systemic lupus erythematosus. Medicine 1993; 72: 113-24.
DOI: https://doi.org/10.1097/00005792-199303000-00005
Hanly JG, Urowitz MB, Su L, Bae SC, Gordon C, Clarke A, et al. Autoantibodies as biomarkers for the predition of neuropsychiatric events in systemic lupus erythematosus. Ann Rheum Dis 2011; 70: 1726-32.
DOI: https://doi.org/10.1136/ard.2010.148502
Bang SY, Choi JY, Park S, Choi J, Hong SJ, Lee HS, et al. Brief report: influence of HLA-DRB1 susceptibility alleles on the clinical subphenotypes of systemic lupus erythematosus in koreans. Arthritis Rheumatol 2016; 68: 1190-6.
DOI: https://doi.org/10.1002/art.39539
Ichinose K, Arima K, Umeda M, Fukui S, Nishino A, Nakashima Y, et al. Predictors of clinical outcomes in patients with neuropsychiatric systemic lupus erythematosus. Cytokine 2016; 79: 31-7.
DOI: https://doi.org/10.1016/j.cyto.2015.12.010
Zhang H, Chambers W, Sciascia S, Cuadrado MJ. Emerging therapies in systemic lupus erythematous: from clinical trial to the real life. Expert Rev Clin Pharmacol 2016; 9: 681-94.
DOI: https://doi.org/10.1586/17512433.2016.1155446
González LA, Ugarte-Gil MF, Alarcón GS. Systemic lupus erythematosus: the search for the ideal biomarker. Lupus 2021; 30: 181-203.
DOI: https://doi.org/10.1177/0961203320979051
Burgos PI, McGwin G Jr, Pons-Estel GJ, Reveille JD, Alarcón GS, Vilá LM. US patients of hispanic and african ancestry develop lupus nephritis early in the disease course: data from LUMINA, a multiethnic US cohort (LUMINA LXXIV). Ann Rheum Dis 2011; 70: 393-4.
DOI: https://doi.org/10.1136/ard.2010.131482
Danila MI, Pons-Estel GJ, Zhang J, Vilá LM, Reveille JD, Alarcón GS. Renal damage is the most important predictor of mortality within the damage index: data from LUMINA LXIV, a multiethnic US cohort. Rheumatology (Oxford) 2009; 48: 542-5.
DOI: https://doi.org/10.1093/rheumatology/kep012
Burgos PI, McGwin G Jr, Reveille JD, Vilá LM, Brown EE, Alarcon GS. Is familial lupus different from sporadic lupus? Data from LUMINA (LXXIII), a multiethnic US cohort. Lupus 2010; 19: 1331-6.
DOI: https://doi.org/10.1177/0961203310375264
González-Naranjo LA, Betancur OM, Alarcón GS, Ugarte-Gil MF, Jaramillo-Arroyave D, Wojdyla D, et al. Features associated with hematologic abnormalities and their impact in patients with systemic lupus erythematosus: data from a multiethnic latin american cohort. Semin Arthritis Rheum 2016; 45: 675-83.
DOI: https://doi.org/10.1016/j.semarthrit.2015.11.003
Ugarte-Gil MF, Pons-Estel GJ, Molineros J, Wojdyla D, McGwin G Jr, Nath SK, et al. Disease features and outcomes in united states lupus patients of hispanic origin and their mestizo counterparts in latin america: a commentary. Rheumatology (Oxford) 2016; 55: 436-40.
DOI: https://doi.org/10.1093/rheumatology/kev280
Catoggio LJ, Soriano ER, Imamura PM, Wojdyla D, Jacobelli S, Massardo L, et al. Late-onset systemic lupus erythematosus in latin americans: a distinct subgroup? Lupus 2015; 24: 788-95.
DOI: https://doi.org/10.1177/0961203314563134
Illei G, Tackey E, Lapteva L, Lipsky P. Biomarkers in systemic lupus eritematosus. II markers of disease activity. Arthritis Rheum 2004; 50: 2048-65.
DOI: https://doi.org/10.1002/art.20345
Sarbu MI, Salman-Monte TC, Muñoz R, Lisbona MP, Almiral Bernabe M, Carbonell J. Differences between clinical and laboratory findings in patines with recent diagnosis of SLE according to the positivity of anti-DNA by crithidia luciliae method. Lupus 2015; 24: 1198-203.
DOI: https://doi.org/10.1177/0961203315573852
Heinlen LD, McClain MT, Merrill J, Akbarali YW, Edgerton CC, Harley JB, et al. Clinical criteria for systemic lupus erythematosus precede diagnosis, and associated autoantibodies are present before clinical symptoms. Arthritis Rheum 2007; 56: 2344-51.
DOI: https://doi.org/10.1002/art.22665
Arbuckle MR, James JA, Kohlhase KF, Rubertone MV, Dennis GJ, Harley JB. Development of anti-dsDNA autoantibodies prior to clinical diagnosis of systemic lupus erythematosus. Scand J Immunol 2001; 54: 211-9.
DOI: https://doi.org/10.1046/j.1365-3083.2001.00959.x
Heinlen LD, Ritterhouse LL, McClain MT, Keith MP, Neas BR, Harley JB, et al. Ribosomal P autoantibodies are present before SLE onset and are directed against non-C-terminal peptides. J Mol Med 2010; 88: 719-27.
DOI: https://doi.org/10.1007/s00109-010-0618-1
Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res 2019; 47: D1005-12.
DOI: https://doi.org/10.1093/nar/gky1120
Marchini J, Howie B. Genotype imputation for genome-wide association studies. Nat Rev Genet 2010; 11: 499-511.
DOI: https://doi.org/10.1038/nrg2796
Hochberg MC. Updating the american college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725.
DOI: https://doi.org/10.1002/art.1780400928
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012; 64: 2677-86.
DOI: https://doi.org/10.1002/art.34473
González LA, Toloza SM, McGwin G Jr, Alarcón GS. Ethnicity in systemic lupus erythematosus (SLE): its influence on susceptibility and outcomes. Lupus 2013; 22: 1214-24.
DOI: https://doi.org/10.1177/0961203313502571
Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine 2003; 82: 299-308.
DOI: https://doi.org/10.1097/01.md.0000091181.93122.55
Pons-Estel BA, Catoggio LJ, Cardiel MH, Soriano ER, Gentiletti S, Villa AR, et al. The GLADEL multinational latin american prospective inception cohort of 1,214 patients with systemic lupus erythematosus: ethnic and disease heterogeneity among ‘hispanics’. Medicine (Baltimore) 2004; 83: 1-17.
DOI: https://doi.org/10.1097/01.md.0000104742.42401.e2
Zavala-Miranda MF, Perez-Arias AA, Márquez-Macedo SE, Comunidad-Bonilla RA, Romero-Diaz J, Morales-Buenrostro LE, et al. Characteristics and outcomes of a hispanic lupus nephritis cohort from Mexico. Rheumatology (Oxford) 2023; 62: 1136-44.
DOI: https://doi.org/10.1093/rheumatology/keac407
Riveros Frutos A, Casas I, Rúa-Figueroa I, López-Longo FJ, Calvo-Alén J, Galindo M, et al. Systemic lupus erythematosus in spanish males: a study of the spanish rheumatology society lupus registry (RELESSER) cohort. Lupus 2017; 26: 698-706.
DOI: https://doi.org/10.1177/0961203316673728
Durcan L, O'Dwyer T, Petri M. Management strategies and future directions for systemic lupus erythematosus in adults. Lancet 2019; 393: 2332-43.
DOI: https://doi.org/10.1016/S0140-6736(19)30237-5
Yung S, Chan TM. Mechanisms of kidney injury in lupus nephritis - the role of anti-dsDNA antibodies. Front Immunol 2015; 6: 475.
DOI: https://doi.org/10.3389/fimmu.2015.00475
Gomard-Mennesson E, Fabien N, Cordier JF, Ninet J, Tebib J, Rousset H. Clinical significance of anti-histidyl-tRNA synthetase (Jo1) autoantibodies. Ann N Y Acad Sci 2007; 1109: 414-20.
DOI: https://doi.org/10.1196/annals.1398.047
Benitez O, Busson M, Charron D. Loiseau P. HLA polymorphism in a guarani-indian population from paraguay and its usefulness for the hispano-indian admixture study in paraguay. Int J Immunogenet 2011; 38: 7-11.
DOI: https://doi.org/10.1111/j.1744-313X.2010.00959.x
Montero-Martín G, Mallempati KC, Gangavarapu S, Sánchez-Gordo F, Herrero-Mata MJ, Balas A, et al. High-resolution characterization of allelic and haplotypic HLA frequency distribution in a spanish population using high-throughput next-generation sequencing. Hum Immunol 2019; 80: 429-36.
DOI: https://doi.org/10.1016/j.humimm.2019.02.005
Zhang M, Lin S, Yuan X, Lin Z, Huang Z. HLA-DQB1 and HLA-DRB1 variants confer susceptibility to latent autoimmune diabetes in adults: relative predispositional effects among allele groups. Genes (Basel) 2019; 10: 710.
DOI: https://doi.org/10.3390/genes10090710
Alshiekh S, Zhao LP, Lernmark Å, Geraghty DE, Naluai ÅT, Agardh D. Different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. HLA 2017; 90: 95-101.
DOI: https://doi.org/10.1111/tan.13065
Lagha A, Messadi A, Boussaidi S, Kochbati S, Tazeghdenti A, Ghazouani E, et al. HLA DRB1/DQB1 alleles and DRB1-DQB1 haplotypes and the risk of rheumatoid arthritis in tunisians: a population-based case-control study. HLA 2016; 88: 100-9.
DOI: https://doi.org/10.1111/tan.12855
Niu Z, Zhang P, Tong Y. Value of HLA-DR genotype in systemic lupus erythematosus and lupus nephritis: a meta-analysis. Int J Rheum Dis 2015; 18: 17-28.
DOI: https://doi.org/10.1111/1756-185X.12528
Diaz Gallo LM, Lundström E, Oke V, Elvin K, Wu YL, Gustafsson J, et al. S4D:6 SLE comprises four immune-phenotypes, which differ regarding HLA-DRB1 and clinical associations. Lupus Sci Med 2018; 5: doi: 10.1136/lupus-2018-abstract.25.
DOI: https://doi.org/10.1136/lupus-2018-abstract.25
Vasconcelos C, Carvalho C, Leal B, Pereira C, Bettencourt A, Costa PP, et al. HLA in portuguese systemic lupus erythematosus patients and their relation to clinical features. Ann N Y Acad Sci 2009; 1173: 575-80.
DOI: https://doi.org/10.1111/j.1749-6632.2009.04873.x
Rasouli-Saravani A, Tahamoli-Roudsari A, Behzad M, Hajilooi M, Solgi G. Clinical relevance of HLA-DRB1 and -DQB1 alleles in iranian systemic lupus erythematosus patients. Iran J Allergy Asthma Immunol 2021; 20: 67-75.
DOI: https://doi.org/10.18502/ijaai.v20i1.5413
Drakoulogkona O, Barbulescu AL, Rica I, Musetescu AE, Ciurea PL. The outcome of patients with lupus nephritis and the impact of cardiovascular risk factors. Curr Health Sci J 2011; 37: 70-4.
Fredi M, Cavazzana I, Quinzanini M, Taraborelli M, Cartella S, Tincani A et al. Rare autoantibodies to cellular antigens in systemic lupus erythematosus. Lupus 2014; 23: 672-7.
DOI: https://doi.org/10.1177/0961203314524850
Arroyo-Avila M, Santiagos-Casas Y, McGwin G, Cantor R, Petri M, Rmasey-Goldman R et al. Clinical associations of anti-smith antibodies in profile: a multi-ethnic lupus cohort. Clin Rheumatol 2015; 34: 1217-23.
DOI: https://doi.org/10.1007/s10067-015-2941-y
Sassi RH, Hendler JV, Piccoli GF, Gasparin AA, da Silva Chakr RM, Brenol JC, et al. Age of onset influences on clinical and laboratory profile of patients with systemic lupus erythematosus. Clin Rheumatol 2017; 36: 89-95.
DOI: https://doi.org/10.1007/s10067-016-3478-4
Supporting Agencies
National Council for Science and Technology (CONACyT) of Paraguay .How to Cite
Acosta-Colman, I., Morel, Z., Ayala Lugo, A. ., Jolly, V. ., de Guillén, I. ., Langjahr, P., Vazquez, M., Martínez de Filártiga, M. ., & Acosta, M. (2023). Clinical features and genetic biomarkers associated with different phenotypes of systemic lupus erythematosus in Paraguayan patients. Reumatismo, 75(2). https://doi.org/10.4081/reumatismo.2023.1541
Copyright (c) 2023 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.