Autoantibodies and Gastrointestinal Symptoms in Colombian Children with Juvenile Idiopathic Arthritis.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is the most common inflammatory joint disease in children. JIA and autoimmune inflammatory Gastrointestinal (GI) diseases share common etiologic mechanisms, including genetic predisposition and environmental influences. OBJECTIVE: To Investigate association between gastrointestinal, rheumatologic clinical variables and the presence of autoantibodies in patients with JIA in treatment. METHODOLOGY: In a cross-sectional study of patients with JIA according to diagnostic criteria and the ILAR classification. GI symptoms and autoantibody expression were evaluated with respect to their association with JIA clinical variables. Anti-Saccharomyces Cerevisiae IgG/IgA (ASCA), 6 antigen associated with anti polymorphonuclear neutrophil (ANCA), anti Transglutaminase (tTG) IgG/IgA, anti deaminated gliadin peptide (DGP) IgG/IgA autoantibodies, ANAS and IgA were measured in all patients. The association between clinical variables and auto-antibodies were evaluated using the Fisher test with significant value of p <0.05. The study was approved by the ethics committee of the all institutions. RESULTS: Samples were collected from ninety-seven patients, 63% of whom were female. The average age was 14 years. The JIA subtype associated with the most common GI symptoms was enthesitis- related arthritis. Of these patients, 44.3% and 14% reported abdominal pain and diarrhea, respectively. Anti-DPG and anti-tTG antibodies were found in 9.28% and 7.22%, respectively and 11.34% were positive for p-ANCA, and 2% were positive for ASCA. CONCLUSION: GI symptoms and autoantibodies associated with inflammation of the GI mucosa were detected in JIA patients but were not associated with autoantibodies or clinical variables. However, it is the monitoring of these patients diagnosis is important.

Improving skills in pediatric rheumatology in Colombia: a combined educational strategy supported by ILAR.

Colombia is a densely populated country with a small number of pediatric rheumatology specialists, including 14 specialists for a population of 1,927,000 children in 2014. The objective of the study was to improve the skills required for early identification, timely referral, and management of musculoskeletal diseases, especially juvenile idiopathic arthritis (JIA), in a group of pediatricians and pediatric residents in a remote region of Colombia. Supported by grant programs developed by the International League of Associations for Rheumatology (ILAR), a combined educational strategy (blended learning) was implemented based on two classroom educational activities and four online modules. The students' acquired knowledge and perception of the strategy were evaluated. Scores were reported as median values and interquartile ranges (IQR), and the differences between scores were estimated using the Wilcoxon test for equal medians. Forty-one students were enrolled, 37 completed the online modules, and 33 attended the final in-person session. The results of the written tests demonstrated an improved ability to solve clinical problems compared with the results of the tests before the course (the median initial vs. final test scores 3 (IQR = 1) vs. 5 (IQR = 0), p = 0.000). The students reported high levels of satisfaction related to compliance with the proposed objectives, the relevance of the contents and activities performed, and the impact on everyday practice. These types of strategies are useful as tools for continuing medical education. However, the results pertain only to short-term learning. It is necessary to evaluate their impact on "lifelong learning."

Association of polymorphic variants of PTPN22, TNF and VDR genes in children with lupus nephritis: A study in Colombian family triads.

INTRODUCTION: Systemic lupus erythematosus is an autoimmune disease in which the severity varies according to race, sex and age of onset. This variation is also observed in the genetic markers associated with the disease, including PTPN22, VDR and TNF genes. The genetic stratification in different populations worldwide can influence the variability. OBJECTIVE: To analyze the heritability of PTPN22, VDR and TNF genetic variants and their association with pediatric lupus nephritis in Colombian families. MATERIALS AND METHODS: We conducted a family-based study including 46 triads (case, father and mother). The variants rs2476601 of PTPN22; rs361525 and rs1800629 of TNF, and TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] and FokI [rs2228570] of VDR were genotyped by qPCR. The effects of overtransmission of the risk allele from parents to children and linkage disequilibrium at the VDR and TNF loci were estimated. RESULTS: We found that allele A of rs2476601 in PTPN22 was distributed among 8.69 % (n=16) of the parents and 19.5 % (n=18) of the cases; this allele was overtransmitted from parents to children 17 times more often than the G allele (p=0.028). TNF and VDR polymorphisms did not exhibit transmission disequilibrium. VDR TaqI, ApaI and BsmI variants exhibited linkage disequilibrium. CONCLUSION: These findings showed an association between the PTPN22 rs2476601 polymorphism and pediatric lupus nephritis due to its overtransmission in the group of families studied.

Asociación de variantes polimorfas de los genes PTPN22 , TNF y VDR en niños con nefritis lúpica: un estudio de tríos en familias colombianas / Association of polymorphic variants of PTPN22 , TNF and VDR genes in children with lupus nephritis: A study in Colombian family triads

RESUMEN Introducción. El lupus eritematoso sistémico es una enfermedad autoinmunitaria cuya gravedad varía según la raza, el sexo y la edad de aparición. Esta disparidad también se observa en los marcadores genéticos asociados con la enfermedad presentes en los genes PTPN22, VDR y TNF. La estratificación genética que presentan las diferentes poblaciones en el mundo puede influir en dicha variabilidad. Objetivo. Analizar la asociación de variantes genéticas de los genes PTPN22, VDR y TNF con nefritis lúpica en niños y su caracter de hereditarias en familias colombianas. Materiales y métodos. Se llevó a cabo un estudio basado en familias con 46 tríos (caso, padre y madre). Se hizo la genotipificación de las variantes rs2476601 de PTPN22, rs361525 y rs1800629 del TNF, y TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] y FokI [rs2228570] del VDR, mediante reacción en cadena de la polimerasa cuantitativa (quantitative Polymerase Chain Reaction, qPCR). Se estimó el efecto de la transmisión del alelo de riesgo de padres a hijos y el desequilibrio de ligamiento de los loci VDR y TNF. Resultados. Se observó que el alelo A de rs2476601 en PTPN22 se distribuyó en 8,69 % (n=16) de los padres y en 19,5 % (n=18) de los casos, y que su transmisión de padres a hijos fue 17 veces mayor con relación al alelo G (p=0,028). Los polimorfismos de TNF y VDR no presentaron desequilibrio de transmisión. Las variantes TaqI, ApaI y BsmI del VDR presentaron desequilibrio de ligamiento. Conclusión. Estos hallazgos evidenciaron una asociación del polimorfismo rs2476601 de PTPN22 con la nefritis lúpica en niños, determinada por su transmisión en el grupo de familias estudiadas.

ABSTRACT Introduction: Systemic lupus erythematosus is an autoimmune disease in which the severity varies according to race, sex and age of onset. This variation is also observed in the genetic markers associated with the disease, including PTPN22, VDR and TNF genes. The genetic stratification in different populations worldwide can influence the variability. Objective: To analyze the heritability of PTPN22, VDR and TNF genetic variants and their association with pediatric lupus nephritis in Colombian families. Materials and methods: We conducted a family-based study including 46 triads (case, father and mother). The variants rs2476601 of PTPN22; rs361525 and rs1800629 of TNF, and TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] and FokI [rs2228570] of VDR were genotyped by qPCR. The effects of overtransmission of the risk allele from parents to children and linkage disequilibrium at the VDR and TNF loci were estimated. Results: We found that allele A of rs2476601 in PTPN22 was distributed among 8.69 % (n=16) of the parents and 19.5 % (n=18) of the cases; this allele was overtransmitted from parents to children 17 times more often than the G allele (p=0.028). TNF and VDR polymorphisms did not exhibit transmission disequilibrium. VDR TaqI, ApaI and BsmI variants exhibited linkage disequilibrium. Conclusion: These findings showed an association between the PTPN22 rs2476601 polymorphism and pediatric lupus nephritis due to its overtransmission in the group of families studied.

Polimorfismos de citoquinas en lupus eritematoso sistemico / Polymorphism of cytokines in systemic lupus erytematosus

El lupus eritematoso sistémico (LES) es una enfermedad poligénica, caracterizada por la activación policlonal de las células B, formación de inmunocomplejos, alteración de la depuración de éstos y una respuesta inflamatoria multisistémica. La influencia genética en LES ha sido reconocida a través de múltiples estudios, inicialmente por la variabilidad del complejo mayor de histocompatibilidad (MHC), y actualmente en genes asociados con inmunidad fuera de este complejo, donde las citoquinas han adquirido especial importancia. Los polimorfismos en los genes de citoquinas se relacionan con diferentes niveles de expresión y producción de las mismas, participando en la físiopatología de la enfermedad en tres aspectos básicos: I. Disbalance Thl/Th2. Se han documentado niveles elevados de IL-4, IL-6, e IL-10 en LES, lo que favorecería la respuesta Th2. Participa también en este proceso IFNy, cuyos niveles séricos variables durante el curso de la enfermedad favorecen Thl al inicio y Th2 en fases tardías. Finalmente TGFp, que coestimula las células reguladoras T naive activadoras para ser células Thl o Th2. 2. Activación persistente de la células B, relacionada con el factor activador de célula B (BAFF), el cual es regulado positivamente por IFN-y e IL-10, IL-6. 3. Defectos en la tolerancia IFNy han sido implicados, alterando la tolerancia a autoantígenos por aumento de la expresión de MHC clase II. Adicionalmente, se han descrito asociaciones con manifestaciones de la enfermedad, así TNFa e IFNy e IL-10 con nefritis lúpica, IL-6 -174 G/C con lupus discoide cutáneo. Esta revisión muestra la participación de los polimorfismos de citoquinas en LES, una enfermedad con una incidencia creciente, considerada modelo de autoinmunidad