ABSTRACT
OBJECTIVES: Anti-glutathione S transferase T1 (GSTT1) antibodies, a type of non-HLA antibody, have been associated with chronic hepatic graft rejection. Despite the presence of this enzyme in the kidney, there are not enough studies on the development of anti-GSTT1 antibodies and their impact on renal grafts. Our objective was to evaluate the presence of anti-GSTT1 antibodies after renal transplant and their impact on graft outcomes. MATERIALS AND METHODS: We conducted an ambispective cohort study. We performed real-time polymerase chain reaction to screen for GSTT1 alleles in 293 recipients and their donors. In null GSTT1 (GSTT1*0) genotype recipients of GSTT1-positive donors, the presence of anti-GSTT1 antibodies was evaluated using indirect immunofluorescence and Luminex assays, and their effects on graft function were evaluated. The median follow-up period was 54.3 months. RESULTS: Of the 293 patients studied, 42 recipients (14.4%) with GSTT1-positive donors did not have the GSTT1 allele (GSTT1-positive donor/GSTT1*0 recipient). Using Luminex assay, we detected antibodies in 16 patients (38.1%), 12 of which were already present at the time of transplant. Of these cases, 37.5% with antibodies had undergone a previous renal transplant. Using indirect immunofluorescence, we found that only 12 patients tested positive, 4 at the time of transplant. Antibody presence did not effect graft glomerular filtration rates or graft loss at 1 year, at 2 years, or end of follow-up. CONCLUSIONS: The presence of anti-GSTT1 antibodies is frequent in renal transplant GSTT1*0 recipients of GSTT1-positive donors but has no effects on graft outcome.
Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Cohort Studies , Treatment Outcome , Tissue Donors , Kidney , AntibodiesABSTRACT
BACKGROUND AND OBJECTIVES: celiac disease is associated with the HLA class II alleles: DQA1*05-DQB1*02 and DQB1*0302. The genetic risk for celiac disease may depend on the presence or absence of such alleles, their combination or number of copies. This study aimed to establish the differences in HLA genotypes between celiac patients diagnosed during childhood and adulthood, and between patients and healthy controls, and to determine the risk of disease in each genotypic category. METHODS: we classified 350 celiac patients at time of diagnosis and 218 controls into 14 categories according to their HLA genotype, based on the presence or absence of risk alleles. RESULTS: we found statistically significant differences between the genotype frequencies of celiac patients diagnosed as being children and adults. DQA1*05 (x 1 copy), DQB1*02 (x 1 copy), DQB1*0302 (x 0 copies) was the most frequent genotype in individuals diagnosed in childhood, whereas DQA1*05 (x 1 copy), DQB1*02 (x 2 copies), DQB1*0302 (x 0 copies) was the most frequent in adults. The risk for disease in each genotypic category in celiac children and adults turned out to be different. The presence of DQB1*0302 did not increase risk in children, but did in adults. CONCLUSION: in our celiac population, we found a different genetic pattern according to age of diagnosis. That could suggest that the pathogenic mechanism of the disease is not exactly the same in both age groups, which could somehow determine clinical presentation of the disease, its epidemiology, coexisting diseases, and complications.
Subject(s)
Celiac Disease/diagnosis , Celiac Disease/genetics , HLA-DQ Antigens/genetics , Adolescent , Adult , Age of Onset , Aged , Alleles , Case-Control Studies , Celiac Disease/epidemiology , Child , Female , Genotype , Humans , Male , Middle Aged , Risk Assessment , Spain/epidemiology , Young AdultABSTRACT
Background and objectives: celiac disease is associated with the HLA class II alleles: DQA1*05-DQB1*02 and DQB1*0302. The genetic risk for celiac disease may depend on the presence or absence of such alleles, their combination or number of copies. This study aimed to establish the differences in HLA genotypes between celiac patients diagnosed during childhood and adulthood, and between patients and healthy controls, and to determine the risk of disease in each genotypic category. Methods: we classified 350 celiac patients at time of diagnosis and 218 controls into 14 categories according to their HLA genotype, based on the presence or absence of risk alleles. Results: we found statistically significant differences between the genotype frequencies of celiac patients diagnosed as being children and adults. DQA1*05 (x 1 copy), DQB1*02 (x 1 copy), DQB1*0302 (x 0 copies) was the most frequent genotype in individuals diagnosed in childhood, whereas DQA1*05 (x 1 copy), DQB1*02 (x 2 copies), DQB1*0302 (x 0 copies) was the most frequent in adults. The risk for disease in each genotypic category in celiac children and adults turned out to be different. The presence of DQB1*0302 did not increase risk in children, but did in adults. Conclusion: in our celiac population, we found a different genetic pattern according to age of diagnosis. That could suggest that the pathogenic mechanism of the disease is not exactly the same in both age groups, which could somehow determine clinical presentation of the disease, its epidemiology, coexisting diseases, and complications (AU)
Subject(s)
Humans , Male , Female , Celiac Disease/complications , Celiac Disease/diagnosis , Celiac Disease/genetics , Autoimmunity/genetics , Autoimmunity/immunology , HLA Antigens/analysis , Histocompatibility Testing/methods , Retrospective Studies , GenotypeABSTRACT
Introducción. Se han observado cambios característicos en las poblaciones de linfocitos intraepiteliales (LIE) de la mucosa intestinal en pacientes celiacos infantiles y adultos. Objetivos. Determinar el rango normal de las poblaciones de LIE por citometría de flujo y establecer su rentabilidad diagnóstica en la enfermedad celiaca (EC). Material y métodos. Estudio retrospectivo de 246 niños y 461 adultos con sospecha de EC a los que se había realizado estudio de poblaciones de LIE. El grupo de EC (221 niños y 98 adultos) lo forman individuos con serología celiaca positiva e histología con lesión grado Marsh 1 o mayor. El grupo control (25 niños y 363 adultos) lo constituyen individuos sin lesión intestinal y serología celiaca negativa a los que también se había realizado inmunofenotipo de LIE por citometría de flujo. Resultados. En el grupo de pacientes celiacos se observa un aumento significativo de LIE totales y LIE TCRγδ y un descenso significativo de LIE NK-like en comparación con los grupos control. En función de las curvas ROC, los puntos de corte en la población infantil fueron: %LIE > 14,2%, %LIE TCRγδ > 16,5% y %LIE NK-like < 10,1%. Los puntos de corte en la población adulta fueron: %LIE > 14,2%, %LIE TCRγδ > 16,1% y %LIE NK-like < 4,4%. En ambas poblaciones se obtienen una especificidad y VPP cercano o igual al 100%, con unos CP+ > 5 y CP− < 2 o próximos. Conclusiones. En el presente trabajo se han establecido los valores de corte para los tres parámetros analizados de los LIE. Estos parámetros permiten diagnosticar con una especificidad cercana al 100% la EC en el niño y en el adulto. Los valores de CP+ y CP− obtenidos muestran que estos parámetros son muy útiles en el diagnóstico de EC activa infantil y del adulto. Por lo tanto, el análisis de las poblaciones de LIE por medio de la citometría de flujo es una nueva herramienta diagnóstica de la EC que complementa el estudio anatomopatológico clásico aumentando su especificidad (AU)
Introduction: The intestinal mucosa of children and adult with coeliac disease shows characteristic changes in intraepithelial lymphocyte (IEL) populations. Objectives: Determination of the normal range of IEL populations by flow cytometry and its diagnostic usefulness in coeliac disease (CD). Methods: A retrospective study of 246 children and 461 adults with suspected CD with IEL immunophenotype results. The CD group (221 children and 98 adults) are individuals with positive coeliac serology and a histology lesion Marsh grade 1 or greater. The control group included 25 children and 363 adults without bowel lesion, negative serology and with IEL immunophenotype results. Results: The group of coeliac patients, adults and children, shows a significant increase in total IEL and TCRdeltagamma IEL, and a significant decrease in NK-like IEL compared with control groups. Based on ROC curves, the cut-off in coeliac children was: %IEL >14.2%, %TCRdeltagamma IEL>16.5% and %NK-like IEL<10.1%. The cut-off in the adult coeliac population was: %IEL >14.2%, %TCR IEL>16.1% and %NK-like IEL<4.4%. In both populations the specificity and PPV are close or equal to 100%, a CP+ >5 and a CP− <2 or near. Conclusions: The cut-off values of the LIE population analysed has been established in this study. The values of CP+ and CP− show that these parameters are very useful for the diagnosis of celiac disease in children and adults, with a specificity of approximately 100%. The immunophenotyping of LIE is a very useful technique in the diagnosis of CD, and complements the classical pathological study, thus increasing the specificity (AU)
