Papel de los genes TNFA e IL10 en el desarrollo y manifestaciones clínicas de la artritis psoriásica

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Abstract

RESUMEN Objetivo: Evaluar el impacto de los polimorfismos de los genes TNFA e IL10 y su asociación con el fenotipo clínico de la artritis psoriásica (APs). Materiales y métodos: Se incluyó a 104 individuos venezolanos, no relacionados, agrupados en 52 pacientes con APs, que reunieron los criterios CASPAR, y 52 individuos sanos, sin antecedentes familiares de psoriasis. Los polimorfismos de los genes TNFA e IL10 se determinaron por PCR-SSP. Resultados: El genotipo GA y alelo A del polimorfismo TNFA-238G/A parecen conferir protección contra el desarrollo de APs (OR: 0,31, IC del 95%: 0,92 -1,05, p: 0,02). El genotipo GA del polimorfismo TNFA-308G/A está asociado con una edad de inicio de APs tardía (GA = 60 ± 13,17 arios vs. GG = 43,55 ± 14,29 años; p = 0,002) y el genotipo GG del polimorfismo IL10-1082A/G con un intervalo mayor entre el inicio de la psoriasis y el desarrollo de la APs (GG = 27,4 ± 24,11 años, GA = 5,47 ± 7,23 años, AA = 7,86 ± 8,51 años, p = 0,001). Los genotipos CC de IL10-819 C/T e IL10-592 C/A confieren riesgo de daño a las articulaciones interfalángicas distales (OR: 4,79, p=0,026). Conclusiones: El polimorfismo TNFA-238G/A desempeña un papel importante en el desarrollo de la APs en mestizos venezolanos. Asimismo, los polimorfismos TNFA-308G/A, IL10-1082A/G, -819C/T y -592C/A pueden modificar la expresión clínica de la APs.

Translated abstract

ABSTRACT Objective: To evaluate the impact of polymorphisms of TNF-alpha (TNFA) and IL10 genes and their association with clinical phenotypes of psoriatic arthritis (PsA). Materials and methods: The study included 104 unrelated Venezuelan individuals, grouped into 52 patients with PsA, who fulfilled the CASPAR criteria, and 52 healthy individuals with no family history of psoriasis. The polymorphisms of the TNFA and IL10 genes were determined by Single Specific Primer-Polymerase Chain Reaction (SSP-PCR). Results: The GA genotype and A allele of the TNFA-238G/A polymorphism appears to confer protection against the development of PsA (OR: 0.31, 95% CI: 0.92 -1.05, P=.02). The GA genotype of the TNFA-308G/A polymorphism is associated with a late onset age of PsA (GA = 60± 13.17 years vs. GG = 43.55 ± 14.29 years, P=.002), and the GG genotype of the IL10 -1082A/G polymorphism with a longer time interval between the onset of psoriasis and the development of PsA (GG = 27.4±24.11 years, GA = 5.47±7.23 years, AA=7.86±8.51 years, P=.001). The CC genotypes of IL10-819 C/T and IL10-592 C/A confers risk of damage to distal interphalangeal joints (OR: 4.79, P=.026) Conclusions: The TNFA-238G/A polymorphism plays an important role in the development of PsA in mixed-race Venezuelans. Likewise, TNFA-308 G/A, IL10 -1082 A/G, -819C/T, -592C/A polymorphisms may modify the clinical expression of PsA.

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Most cited references 28

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Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris.

Tilo Henseler, Enno Christophers (1985)

In 2,147 patients suffering from psoriasis, evaluation of the age of onset revealed two peaks, one occurring at the age of 16 years (female) or 22 years (males) and a second peak at the age of 60 years (female) or 57 years (males). Human lymphocyte antigen (HLA) tissue typing in 112 randomly assigned patients showed that HLA-Cw6, known to be at disequilibrium in psoriasis, is present in 85.3% of patients with early onset. In contrast, 14.7% patients with late onset showed this marker. Parents (father or mother) were affected in approximately half of the patients with early onset and in none belonging to the group with late onset. Furthermore, psoriasis in patients with early onset follows an irregular course and shows a strong tendency to become generalized. On the basis of clearly defined criteria (e.g., age of onset, heritability, and clinical course of disease), nonpustular psoriasis shows two distinct forms, one of which is hereditary, with early onset, and the other is sporadic and occurs in older age.

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Interleukin-10 paradox: A potent immunoregulatory cytokine that has been difficult to harness for immunotherapy.

Ankit Saxena, Sam Khosraviani, Sanjeev Noel … (2015)

Interleukin-10 (IL-10) is arguably the most potent anti-inflammatory cytokine. It is produced by almost all the innate and adaptive immune cells. These cells also serve as its targets, indicating that IL-10 secretion and action is highly regulated and perhaps compartmentalized. Consistent with this notion, various efforts directed at systemic administration of IL-10 to modulate autoimmune diseases (type 1 diabetes, multiple sclerosis, rheumatoid arthritis, psoriasis) have produced conflicting and largely inconsequential effects. On the other hand, IL-10 can promote humoral immune responses, enhancing class II expression on B cells and inducing immunoglobulin (Ig) production. Consequently, the high IL-10 level in systemic lupus erythematosus (SLE) patients is considered pathogenic and its blockade ameliorates the disease. In this perspective, we review preclinical findings and results of recent clinical studies using exogenous IL-10 to treat the aforementioned autoimmune diseases. In addition, given the limited success of IL-10 supplementation, we suggest that future studies should be expanded beyond modulating the delivery modes to include developing new strategies to protect and replenish the endogenous sources of IL-10. As an example, we provide evidence that aberrant Fas-mediated deletion of IL-10-producing B cells subverts the immunoregulatory role of IL-10 in autoimmune diabetes and that modulation of the Fas pathway preserves the IL-10-producing B cells and completely protects NOD mice from developing the disease.

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HLA associations reveal genetic heterogeneity in psoriatic arthritis and in the psoriasis phenotype.

Ben Greenberg, Oliver FitzGerald, Brian Kirby … (2012)

Rigorously ascertained cases of psoriatic arthritis in subjects presenting to a rheumatology unit were compared with cases of psoriasis in subjects presenting to a dermatology unit, where subjects with musculoskeletal features were excluded, to address 1) the extent to which the contribution of the major histocompatibility complex (MHC) to psoriatic arthritis susceptibility resembles that in psoriasis, and 2) whether MHC genes determine quantitative traits within the psoriatic arthritis phenotype. Separate discovery and validation subcohorts of patients recruited from a relatively homogeneous population were studied by sequence-based HLA typing, in which frequencies of the HLA-B and HLA-C alleles and haplotypes were compared. In patients with psoriatic arthritis, the frequency of C*06:02 was lower than that in patients with psoriasis (28.7% versus 57.5%; P = 9.9 × 10(-12) ). Three haplotypes containing B*27:05 or B*39:01 were significantly increased in frequency in patients with psoriatic arthritis, but not in those with psoriasis. The structurally related B*39:06 allele was not increased in frequency. B*27 was associated with an interval of 0.98 years between skin and musculoskeletal disease (P = 2.05 × 10(-6) ), compared with an interval of 10.14 years for C*06. Preliminary evidence suggested that B*38:01 and B*08 may be associated with psoriatic arthritis susceptibility, and that allotypes encoding P2 pockets that bind side chains opposite in charge from those encoded by the B*27 and B*39 molecules may exert a protective role. These findings suggest that the psoriasis phenotype results from two patterns of MHC effect. The first involves the classic psoriasis susceptibility gene C*06, which confers more penetrant skin disease with less prevalent and more time-dependent musculoskeletal phenotype development. The second pattern appears to be mediated by HLA-B alleles, notably B*27, and includes temporally more coincident musculoskeletal involvement that is nearly equivalent in penetrance to that of the skin disease. Copyright © 2012 by the American College of Rheumatology.

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Author and article information

Contributors

Freddy Herrera: Role: ND

Luis Gutiérrez: Role: ND

Eva Salazar Alcalá: Role: ND

Omar Balbas: Role: ND

Mercedes Fernández Mestre: Role: ND

Journal

Journal ID (publisher-id): rcre

Title: Revista Colombiana de Reumatología

Abbreviated Title: Rev.Colomb.Reumatol.

Publisher: Asociación Colombiana de Reumatología (Bogotá, Distrito Capital, Colombia )

ISSN (Print): 0121-8123

Publication date (Print and electronic): March 2018

Volume: 25

Issue: 1

Pages: 9-15

Affiliations

[1] Caracas orgnameInstituto Venezolano de Investigaciones Científicas orgdiv1Centro de Medicina Experimental orgdiv2Laboratorio de Fisiopatología Venezuela

[2] Caracas orgnameHospital Clínico Universitario de Caracas orgdiv1Centro Nacional de Enfermedades Reumáticas Venezuela