Health-related quality of life in adults with juvenile idiopathic arthritis / Calidad de vida relacionada con la salud en pacientes adultos con artritis idiopática juvenil

ABSTRACT Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in the paediatric age. It is estimated that between 30-60% of adults patients persist with active disease, which leads to sequelae and complications as well as a decrease functional capacity and reduced quality of life. Objectives: To evaluate the health-related quality of life in adult patients diagnosed with juvenile idiopathic arthritis. Methodology: A cross-sectional study was performed, using a search for adult patients diagnosed with JIA between 1996 and 2018. Clinical records were reviewed during the paediatric age, and clinical parameters were evaluated for activity (JADASc-71), and joint (JADI-A) and extra-articular (JADI-E) damage, functional capacity (HAQ), and quality of life (SF-36). Relationships were determined by non-conditional logistic regression. Results: A total of 69 patients were included. The most frequent subtype of JIA was enthesitis-related arthritis (ERA) (33%). Active disease was observed in 33%. Polyarticular JIA RF (+) was associated with active disease (P = .007), high values of JADASc-71 (P = .003), and HAQ (P = .001). Age of onset after 5 years reduced risk of joint damage (OR = 0.16) and extra-articular damage (OR = 0.03). Poor therapeutic adherence was associated with joint damage (P = .00) and JADASc-71 (P = .004). A high score of JADI-E was associated with functional dis-ability (OR = 5.75). Joint damage (P = .003) and extra-articular damage (P = .024), and functional disability (OR = 7.05) were associated with low values in the SF-36. Conclusions: JIA is not a disease limited to the paediatric age. Persistence of active disease, joint, and extra-articular damage are associated with functional disability and a decrease in H-RQoL.

RESUMEN Introducción: La artritis idiopática juvenil (AIJ) permanece activa en el 30-60% de los pacientes adultos, conduciendo a complicaciones articulares, extraarticulares, disminución en la capacidad funcional y reducción en la calidad de vida. Objetivos: Evaluar la calidad de vida relacionada con la salud en pacientes adultos con diagnóstico de AIJ. Metodología: Estudio corte transversal; se realizó una búsqueda de pacientes adultos con diagnóstico de AIJ entre 1996 y 2018. Se revisaron historias clínicas durante la edad pediátrica y se evaluaron parámetros clínicos para actividad (JADASc-71), daño articular (JADI-A) y extraarticular (JADI-E), capacidad funcional (HAQ) y calidad de vida (SF-36). Asociaciones determinadas por regresión logística no condicional. Resultados: Se incluyó a 69 pacientes. El subtipo de AIJ más frecuente fue la artritis relacionada con la entesitis (ARE) (33%). El 33% de los pacientes tenían enfermedad activa. La AIJ poliarticular FR positivo se asoció a enfermedad persistentemente activa (p = 0,007), altos valores del JADASc-71 (p = 0,003) y HAQ (p = 0,001). La edad de inicio posterior a 5 años redujo el riesgo de daño articular (OR = 0,16) y extraarticular (OR = 0,03). La mala adherencia terapéutica se asoció a daño articular (p = 0,00) y JADASc-71 (p = 0,004). La alta puntuación del JADI-E se asoció a discapacidad funcional (OR = 5,75). El daño articular (p = 0,003) y extraarticular (p = 0,024) y discapacidad funcional (OR = 7,05) se asociaron a bajos valores en SF-36. Conclusiones: La AIJ no es una enfermedad limitada a edad pediátrica. La persistencia de enfermedad activa y el daño articular y extraarticular se asocian a discapacidad funcional y disminución en la calidad de vida relacionada con la salud.

Juvenile polyautoimmunity in a rheumatology setting.

Overt polyautoimmunity (PolyA) corresponds to the presence of more than one well-defined autoimmune disease (AD) manifested clinically in a single patient. The current study aimed to describe the main characteristics of juvenile PolyA in a pediatric rheumatology setting and analyze the chronological aspects, index cases, familial autoimmunity, and clustering pattern. This was a cross-sectional and multicenter study in which 313 children with overt PolyA were included. Patients were systematically interviewed and their medical records reviewed using a questionnaire that sought information about demographic, clinical, immunological, and familial characteristics. A hierarchical cluster analysis was done to determine similarities between autoimmune diseases based on PolyA. PolyA occurred simultaneously in 138 (44%) patients. Multiple autoimmune syndrome was observed in 62 (19.8%) patients. There were 25 index diseases of which, systemic lupus erythematosus (SLE, n = 134, 42.8%), juvenile idiopathic arthritis (JIA, n = 40, 12.7%), Hashimoto's thyroiditis (HT, n = 24, 7.66%), immune thrombocytopenic purpura (ITP n = 20, 6.39%), antiphospholipid syndrome (APS, n = 15, 4.79%), and vitiligo (VIT, n = 15, 4.79%) were the most frequent and represented 79.23% of the total number of patients. Familial autoimmunity influenced PolyA. A high aggregation of autoimmunity was observed (λr = 3.5). Three main clusters were identified, of which SLE and APS were the most similar pair of diseases (based on the Jaccard index) followed by HT and JIA, which were related to ITP and Sjögren's syndrome. The third cluster was composed of localized scleroderma and VIT. Our findings may assist physicians to make an early diagnosis of this frequent condition. Pediatric patients with ADs should be systematically assessed for PolyA.

The Colombian Spanish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Colombian Spanish language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, and construct validity (convergent and discriminant validity). A total of 22 JIA patients (9.1% systemic, 27.3% RF-negative polyarthritis, 36.4% enthesitis-related arthritis, 27.2% other categories) were enrolled in the paediatric centre of Bogota. All JAMAR components revealed good psychometric performances. In conclusion, the Colombian Spanish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

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.

Caracterización del compromiso articular en dermatomiositis juvenil / Characterization of the commitment articulated in Juvenile Dermatomyositis

Introducción: La dermatomiositis juvenil (DMJ) es la miopatía autoinmune más frecuente en pacientes juveniles. Se observan tres tipos de compromiso articular: sinovitis inflamatoria, compromiso funcional por retracciones tendinosas y bloqueo mecánico por calcinosis. El ob-jetivo del estudio es definir el tipo y frecuencia del compromiso articular al inicio y durante el curso de una cohorte de pacientes con DMJ.

Corea lúpica. Prevalencia y expresión clínica / It Korea lupus. Prevalence and clinical expression

Introducción y objetivo: La corea es uno de los subtipos de compromiso neurológico ob-servados al debut y durante el curso del lupus eritematoso sistémico juvenil (LESJ). Origina dificultades de diagnóstico diferencial y puede provocar morbilidad significativa. El objetivo del estudio es describir la prevalencia y curso de corea en una cohorte de pacientes con LESJ. Métodos: Estudio descriptivo y retrospectivo. Se analizaron las características clínicas y se-rológicas de una cohorte de pacientes con LESJ que desarrollaron corea al debut y durante el tiempo de seguimiento.

Infecciones al debut de lupus eritematoso sistémico juvenil / Infections to systemic lupus erythematosus youth debut

ntroducción: Las infecciones son reconocidas como evento disparador de enfermedad au-toinmune y originan complicaciones e interfieren en el tratamiento requerido para el control de actividad lúpica. El objetivo del estudio es describir el patrón de infecciones observadas al debut y su prevalencia en una cohorte de pacientes con lupus eritematoso juvenil (LESJ). Métodos: Estudio descriptivo retrospectivo. De una cohorte de 241 pacientes con LESJ, analizar aquellas cuyo debut coincidió con un evento infeccioso y cuyos datos demográfi-cos, clínicos, serológicos y el tipo y curso de infecciones documentadas fueron registradas.

Manifestaciones mucocutáneas y perfil inmunológico en pacientes con lupus eritematoso sistémico en pediatría / Manifestations of Mucocutaneous and immunological profile in patients with systemic lupus erythematosus in Pediatrics

Introducción: El lupus eritematoso sistémico juvenil (LESJ) es una enfermedad autoinmume cuyas manifestaciones mucocutáneas tienen una expresión clínica variable y su frecuencia varia ampliamente, entre el 10 y el 85%. En la actualidad se incluyen criterios de clasificación de LES al lupus cutáneo agudo, subagudo y crónico, ulceras orales-nasales y la alopecia no cicatrizal.Objetivo: Describir las manifestaciones mucocutáneas y el perfil inmunológico en pacientes con LESJ.

Tiroidopatías autoimmunes juveniles y poliautoinmunidad / Tiroidopatias juvenile autoimmune and poliautoinmunidad

ntroducción y objetivo: Las tiroidopatias autoimmunes juveniles (TAIJ) son las enfermeda-des órgano específicas más comunes y con frecuencia hacen parte de la enfermedad autoin-mune múltiple (EAIM). El objetivo del estudio es determinar el tipo y frecuencia de TAIJ en pacientes con poliautoinmunidad. Métodos: En un registro de pacientes juveniles que du-rante el seguimiento en 13 centros de reumatología pediátrica, han asociado enfermedades autoinmunes (EAI), se identificaron pacientes con TAIJ.

¿Existen diferencias en la expresión clínica del síndrome antifosfolipídico juvenil en función del género? / Are there differences in the clinical expression of the gender youth antiphospholipid syndrome?

Introduccion: El síndrome antifosfolipídico (SAF) condiciona hipercoagulabilidad y pue-de provocar manifestaciones no trombóticas. Se asocia o no a otra enfermedad autoinmune (EAI). En el presente estudio se exploraron diferencias entre géneros en cohortes de pacientes juveniles con SAF. Métodos: Estudio retrospectivo descriptivo. Se revisaron historias clínicas de pacientes con SAF seguidos en 13 centros de reumatología pediátrica en Colombia y en Hospital San Joan (Barcelona, España). Se determinaron variables demográficas y frecuencia de manifestaciones clínicas y resultados serológicos.

Nefritis lúpica juvenil. Espectro clínico y patológico al debut / Juvenile lupus nephritis. Clinical and pathological spectrum debut

Introducción y objetivo: La nefritis lúpica (NL) es más frecuente y severa en pacientes juveni-les. Origina significativa morbi-mortalidad a corto y largo plazo. Las manifestaciones clínicas varían según el tipo histológico. El objetivo del estudio es determinar las características clíni-cas e histológicas al debut de NL. Métodos: Estudio descriptivo retrospectivo en pacientes lúpicos juveniles controlados en cuatro instituciones hospitalarias.

Uveítis crónica en la artritis idiopática juvenil. Impacto pronóstico / Chronic Uveitis in juvenile idiopathic arthritis. Impact forecasting

Introducción y objetivo: La uveitis en la artritis idiopática juvenil (AIJ) es causa de importan-te morbilidad. La cronicidad de inflamación intraocular determina severidad de complicacio-nes y secuelas. El objetivo del estudio es evaluar la extensión, tratamiento y complicaciones de la uveítis crónica en pacientes con AIJ. Métodos: Estudio descriptivo, retrospectivo. Se in-cluyeron pacientes con seguimiento mínimo de 24 meses por oftalmología y reumatología. Se analizaron variables dermográficas, clínicas, complicaciones y tratamiento. La uveitis se eva-luó según clasificación SUN (standardization of uveítis nomenclature).

Esclerodermia localizada juvenil: ¿es una enfermedad benigna? / Juvenile localized scleroderma: is it a benign disease?

Resumen Introducción: La esclerodermia localizada juvenil es una enfermedad polimórfica que ocurre con mayor frecuencia en niñas. Se acompaña de morbilidad importante. El compromiso extradérmico es frecuente y se reportan tasas de poliautoinmunidad de hasta 7%. Al momento, se desconocen las características clínicas de los pacientes colombianos con esta enfermedad. Objetivo: Describir las características clínicas, morbilidades y secuelas en pacientes con diagnóstico de esclerodermia localizada juvenil, en múltiples centros de reumatología pediátrica en Colombia. Materiales y métodos: Estudio descriptivo, retrospectivo y multicéntrico. Pacientes con diagnóstico de esclerodermia localizada juvenil con un mínimo de 1 ario de evolución y 6 meses de seguimiento, en 10 centros de reumatología pediátrica mediante revisión de historias clínicas. Resultados: El n = 88. La distribución por género fue: femenino 2,1; masculino 1. Edad promedio al inicio de la enfermedad 7,1 años (0-14). Promedio de duración de la enfermedad al diagnóstico 16,5 meses (1-96). La distribución por subtipos fue morfea circunscrita (32,9%), mixta (31,8%), linear (21,5%, asciende a 55% al incluir formas mixtas con lesiones lineares) generalizada (11,4%) y panesclerótica (2,3%). Se detectaron alteraciones estéticas en el 91%, alteraciones del crecimiento en 41% y compromiso funcional de articulaciones vecinas en 32%. Se presentó compromiso extradérmico en 22,7% y poliautoinmunidad en 12,5%. Conclusiones: La esclerodermia localizada juvenil es una enfermedad polimórfica e impredecible. En la mayoría de los casos el diagnóstico es tardío. La tasa de compromiso extradérmico sugiere que no es una enfermedad limitada a la piel. Un diagnóstico temprano, tratamiento dinámico y seguimiento cercano permiten prevenir y detectar tempranamente complicaciones derivadas de la enfermedad.

Abstract Introduction: Juvenile localized scleroderma is a polymorphic disease. It is more prevalent in girls and has a significant morbidity. Extra-cutaneous involvement is common, and polyautoimmunity can reach 7%. The clinical characteristics of this disease in Colombian patients are currently unknown. Objective: To describe the clinical characteristics, morbidity and outcomes in patients with juvenile localized scleroderma in different paediatric rheumatology clinics in Colombia. Materials and methods: A descriptive, retrospective, and multicentre study was conducted on patients with juvenile localized scleroderma with a minimum of 1 year of disease onset, and 6 months of follow-up in 10 paediatric rheumatology clinics. Results: The study included 88 patients, with a gender distribution of female 2.1: male 1. Mean age at disease onset was 7.1 years (0-14). Mean disease duration at diagnosis was 16.5 months (1-96). Sub-type distribution was, circumscribed (32.9%), mixed (31.8%), and linear (21.5%, that increased to 55% if linear lesions of the mixed subtype are included), generalised (11.4%), and pan-sclerotic morphea (2.3%). Aesthetic compromise was detected in 91%, with growth disturbances in 41%, and joint functional compromise in 32%. Extra-cutaneous involvement occurred in 22.7% and polyautoimmunity in 12.5%. Conclusions: Juvenile localized scleroderma is a polymorphic and unpredictable disease. It diagnosed late in most of the cases. Extra-cutaneous involvement suggests that is not a disease limited to skin. An early diagnosis, a dynamic treatment and a close follow-up helps to prevent, and detect, complications arising from the disease.

Porphyromonas Gingivalis and IgG1 and IgG2 Subclass Antibodies in Patients with Juvenile Idiopathic Arthritis.

PURPOSE: The purpose of this study was to evaluate the periodontal status and the presence and concentration of Porphyromonas gingivalis (P. gingivalis) and immunoglobulin G (IgG) subclass against P. gingivalis in juvenile idiopathic arthritis (JIA) and its association with rheumatic clinical activity parameters. METHODS: Rheumatologic conditions and periodontal status were clinically assessed in 51 patients with JIA. P. gingivalis, IgG1 and IgG2, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs), and human leukocyte antigen B27 were also evaluated. RESULTS: Periodontitis was observed in 21.5 percent of the patients, 23.5 percent of whom were positive for P. gingivalis, which was associated with enthesitis-related arthritis (P<0.035). IgG1 against P gingivalis was associated with RF autoantibodies (P=0.05), and all patients positive for ACPAs had higher anti-P gingivalis IgG1 levels. A significant correlation was found between the presence of limited joint mobility and the plaque index in polyarticular JIA (r=0.55, P=0.028). CONCLUSIONS: An association between IgG and rheumatic disease activity markers in JIA was evident. It is important to investigate the familiar periodontal status and clinical course in JIA, especially in enthesitis-related arthritis.

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.

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.

Biomarcadores genéticos de los sistemas MHC/HLA-DRB1* y PTPN22 asociados a enfermedad reumática: artritis idiopática juvenil y artritis reumatoide de instalación temprana. Un enfoque analítico en un estudio piloto / Genetics Biomarckers off the MHC/HLA-DRB1* and PTPN 22 Systems Associated to Rheumatics diseases: idiopatic juvenile arthritis and rheumatoid of early installation. A descriptive approach in a pilot study

Objetivos: Identificar biomarcadores de susceptibilidad para AIJ poliarticular y AR de instalación temprana por estudio del polimorfismos de MHC/HLA-DRB1* y PTPN22. Materiales y métodos: Se realizó un estudio de casos y controles con una relación 1:2. Todos los sujetos de investigación y los controles provinieron de una corta anidada perteneciente a un proyecto institucional; 30 pacientes con AIJ y 30 con AR de instalación temprana. Como controles se estudiaron 60 individuos sanos. El ADN se obtuvo por salting out modificado. La tipificación de los alelos MHC/DRB1* se realizó por PCR-SSP y en el polimorfismo (C1858T) del sistema PTPN22 se utilizó PCR-RTq. Resultados: Para AIJ Poliarticular, el alelo DRB1*0404 se asoció con susceptibilidad (OR=10.82; p<0.05), en el grupo con AR de instalación temprana, DRB1*0101 se mostró como marcador de susceptibilidad (OR=4.04; p<0.05). Se destaca que el alelo HLA-DRB1*0701 aparece como marcador protector para ambas patologías (OR=0,15; p<0,05). El polimorfismo del SNP (C1858T) PTPN22 no se asoció con AIJ Poliarticular. En contraste, en AR de instalación temprana, el Alelo CC se asoció con protección p<0.05. En el mismo grupo, CT/TT se mostró como un marcador de susceptibilidad <0.05. El análisis de la secuencia aminoacídica 70QRRAA74 del epítope compartido se asoció con susceptibilidad para ambas entidades (p<0.05) y la secuencia 70DRRGQ74 con protección en ambos grupos de pacientes (p<0.05). Conclusión: Se destaca que en la asociación con la secuencia del epítope compartido, la ubicación del tipo de aminoácido y posición del mismo define probable asociación como marcador molecular de susceptibilidad en ambas entidades. Los polimorfismos compartidos sugieren un origen genético común para ambas entidades.

Objectives: To identify polymorphisms of MHCIHLA-DRB1* and PTPN22 systems as a genetic biomarker of susceptibility to JIA poliarticular and early installation RA. Material and methods; This was a pilot case control study with a relation of 1:2. Patients and control individuals involved in this study were selected from a nested cohort from an institutional previous RAIJIA project. The sample was represented by thirty patients with JIA and 30 diagnosed with early installation RA. Sixty unrelated healthy individuals were involved as a control DNA Isolation was obtained by a modified salting out technique. The oligotyping of the MHCIDRB1* alleles was performed by PCR-SSP and the typing of the PTPN22 polymorphism was done by RT-PCR. Results: The DRB1*0404 allele was associated with susceptibility to JIA(OR=10.82, P<0.05). In the early installation RA group the DRB1*0101 allele was showed as a marker of susceptibility to JIA patients (OR=4.04, P<0.05). It is noteworthy that the HLA-DRB1*0701 appears as a possible protective marker for both diseases (OR=015, p<0.05). The polymorphism of (C1858T)PTPN22 was not associated with poliarticular JIA. In contrast, in the early installation RA group of patients, the CC PTPN22 polymorphism was found to be as a protective marker (p<0.05). On the other hand, the amino acid sequence 70QRRAA74 of the share epitope was a marker for susceptibility to both entities (p<0.05) By contrast, the sequence 70DRRGQ74 of the same epitope was showed as a possible marker for protection on both entities (p<0.05.). Conclusion: The model that was used for searching association between the shared epitope -region 70-74 of the DRB1* alleles and these two entities showed the importance of the location and also the type of amino acid in those positions. The polymorphisms found as molecular markers of susceptibility for both entities suggested a common origin and could suggest its probable roll as a molecular marker of susceptibility.

Sarcoidosis en pediatría: reporte de 7 casos / Pediatric sarcoidosis: a report of seven cases

La sarcoidosis es una enfermedad granulomatosa crónica de origen no infeccioso que puede comprometer diversos órganos. Su prevalencia es baja, y en Colombia se han reportado casos de manera aislada. Su etiología y fisiopatología aún no se conocen completamente. La presentación clínica y las diferentes manifestaciones de la enfermedad son variables. Cuando su debut se presenta en niños menores de 5 años se denomina sarcoidosis de inicio temprano, mientras que cuando lo hace en niños mayores de 5 años recibe el nombre de sarcoidosis de inicio tardío. En este reporte de caso se presentan 7 pacientes pediátricos, de los cuales 5 correspondieron a sarcoidosis de inicio temprano y 2 a sarcoidosis de inicio tardío. Todos los pacientes tuvieron un diagnóstico tardío de la enfermedad, manifestaciones de varios órganos y sistemas, y recibieron tratamiento inmunosupresor. Cuatro tuvieron curso crónico, 2 remisiones de la enfermedad y 1 recaídas frecuentes. Fue llamativa una asociación poco usual de 2 pacientes con sarcoidosis de inicio temprano quienes adicionalmente presentaron la enfermedad de Ollier.

Sarcoidosis is a chronic granulomatous disease of non-infectious origin which can involve various target organs. Its prevalence is low and there have been only isolated cases reported in Colombia. Its etiology and pathophysiology are not well known. The clinical presentation and signs of the disease vary. When its onset is before five years of age it is recognized as early onset sarcoidosis, while if its onset is after five years of age it is called late onset sarcoidosis. In this case report all patients had a delayed diagnosis and they presented with a multiple organ involvement which required an immunosuppressive treatment. Of the 7 patients, 4 had a chronic course, 2 had remission, and 1 with frequent relapses of the disease. There was an unusual relationship of two patients with early onset disease who additionally presented with Ollier's disease.

HLA-DRB1 alleles and HLA-DRB1 shared epitopes are markers for juvenile rheumatoid arthritis subgroups in Colombian mestizos.

We studied the association of human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 alleles and HLA haplotypes with juvenile rheumatoid arthritis (JRA) in 65 patients and 65 controls from Colombia. The JRA subsets were distinguished on the basis of criteria established by the American College of Rheumatology. Two alleles were associated with protection, HLA-DRB1*1501 (p = 0.002) and HLA-DRB1*1402 (p = 0.01). HLA-DRB1*1602 (p = 0.0000002) was associated with susceptibility for systemic JRA and HLA-DRB1*1104 (p = 0.0002) for pauciarticular JRA. Amino acid sequences at residues 70-74 of DRB1 chain shared by HLA-DRB1 alleles (shared epitomes) were also informative. The polyarticular JRA subset revealed association with (70)QRRAA(74), which includes HLA-DRB1*04, 01, and (70)DRRAA(74), which includes DRB1*1601, 1602, 1101, and 1104. Two new findings of interest were the association of the haplotypes DRB1*1104, DQB1*0301(p = 0.0002) with pauciarticular JRA and DRB1*1602, DQB1*0301 (p = 0.0000002) association with systemic JRA. The DRB1 alleles of these two haplotypes share the epitope (70)DRRAA(74)and were associated with both the pauciarticular and the systemic subset of JRA. Our results suggest that studies of disease susceptibility in populations of admixed genetic background should take into account the contribution of different ethnic groups or nationalities in the recruitment of controls and patients studied in order to rule out genetic stratification.

[Polymorphism of human HLA-DRB1 leukocyte antigen alleles and its association to juvenile rheumatoid arthritis in a sample of Colombian mestizo children]. / Polimorfismo de los alelos de los antígenos de leucocitos humanos HLA-DRB1 y su asociación con la artritis reumatoidea juvenil en una muestra de niños mestizos colombianos.

Oligotypes of the human leukocyte antigen HLA Class II, DRB1 alleles were characterized at the molecular level in a group of Colombian children suffering juvenile rheumatoid arthritis (JRA). The distribution of these alleles was examined in a group of Colombian mestizo children (genetic admixture of Amerindians, Europeans and Africans) suffering from clinically distinct JRA subsets in order to detect HLA allele frequency differences in patients with different JRA subsets. A group of 65 patients with JRA and 65 controls were characterized for the subtypes of the HLA-DRB1 alleles using polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP). The oligotyping protocol recommended by the 12th International Histocompatibility Workshop held in St. Malo, Paris, in 1996, was used. Subtype HLA-DRB1*1104 was the allele most strongly associated with susceptibility to JRA (Fisher's p = 0.013, odds ratio (OR) = 16.79, etiologic fraction (EF) = 0.93). HLA-DRB1*1602 was also associated with susceptibility to a lesser degree (Fisher's p = 0.016, OR = 8.98, EF = 0.88). HLA-DRB1 alleles participating in JRA protection were HLA-DRB1*1501 (preventive fraction (PF) = 0.466, p = 0.005) and HLA DRB1*1402 (PF = 0.49, p = 0.009). The relationship between some HLA-DRB1 alleles and clinical features was also compared. The presence of rheumatic factor was associated with the alleles HLA-DRB1*0407 (p = 0.05, OR = 11.2, EF = 0.45) and HLA-DRB1*1302 (p = 0.02, OR = 22.8, EF = 0.63). There was also an association between HLA-DRB1*0701 (p = 0.001, OR = 58, EF = 0.73) with expressing ANA +. We found that in the oligoarticular subset, the allele HLA-DRB1*1104 (p = 0.0034, OR = 41.53, EF = 0.97) was the one expressed most commonly. In the poliarticular group, the alleles most frequently expressed were HLA-DRB1*0404 (Fisher's p = 0.012, OR = 8.75, EF = 0.88). In patients with systemic JRA, the HLA-DRB1*1602 allele (p = 0.005, OR = 21.33, EF = 0.95) was most frequent. These results suggested that the MHC genes of mestizo children influence not only the clinical expression of the disease, but also the susceptibility to its development.