RESUMO
Bifidobacterium infantis NLS super strain (B. infantis NLS-SS) was previously shown to alleviate gastrointestinal symptoms in newly diagnosed coeliac disease (CD) patients consuming gluten. A high proportion of patients following a gluten-free diet experiences symptoms despite dietary compliance. The role of B. infantis in persistently symptomatic CD patients has not been explored. The aim of the study was to evaluate the effect of B. infantis NLS-SS on persistent gastrointestinal symptoms in patients with CD following a long-term GFD. We conducted a randomised, cross-over, double-blind, placebo-controlled trial in symptomatic adult CD patients on a GFD for at least two years. After one-week run-in, patients were randomised to B. infantis NLS-SS or placebo for 3 weeks with cross-over after a 2-week wash-out period. We estimated changes (Δ) in celiac symptom index (CSI) before and after treatment. Stool samples were collected for faecal microbiota analysis (16S rRNA sequencing). Gluten immunogenic peptide (GIP) excretion in stool and urine samples was measured at each study period. Eighteen patients were enrolled; six patients were excluded due violations in protocol. For patients with the highest clinical burden, CD symptoms were lower in probiotic than in placebo treatment (P=0.046). B. infantis and placebo treated groups had different microbiota profiles as assessed by beta diversity clustering. In probiotic treated groups, we observed an increase in abundance of B. infantis. Treatment with B. infantis was associated with decreased abundance of Ruminococcus sp. and Bifidobacterium adolescentis. GIP excretion in stools and urine was similar at each treatment period. There were no differences in adverse effects between the two groups. B. infantis NLS-SS improves specific CD symptoms in a subset of highly symptomatic treated patients (GFD). This is associated with a shift in stool microbiota profile. Larger studies are needed to confirm these findings. ClinicalTrials.gov: NCT03271138.
Assuntos
Bifidobacterium longum subspecies infantis , Doença Celíaca/terapia , Dieta Livre de Glúten , Microbioma Gastrointestinal , Probióticos/uso terapêutico , Adulto , Carga Bacteriana , Bifidobacterium longum subspecies infantis/crescimento & desenvolvimento , Doença Celíaca/dietoterapia , Doença Celíaca/microbiologia , Estudos Cross-Over , Método Duplo-Cego , Fezes/química , Fezes/microbiologia , Feminino , Glutens/análise , Glutens/urina , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/urina , Ruminococcus/crescimento & desenvolvimentoRESUMO
AIM: To evaluate the ability of interleukin (IL)-15 to control T cell functions through its influence on CD30 and OX40 expressing cells in Celiac Disease (CD). In peripheral blood (PB), by examining the expression of OX40 in conventional effectors cells and T cells with a phenotypic specialization of regulatory cells [CD4+CD25high forkhead box protein 3 (Foxp3)+], and the co stimulation of IFN-γ and IL-4 production within CD30 and OX40 positive subsets of T cells. At the duodenal mucosa, by assessing the expression of CD30 and OX40 in intraepithelial (IE) and lamina propria (LP) lymphocytes (IEL, LPL). PATIENTS AND METHODS: PB and duodenal mucosal biopsies were obtained from 38 patients with classic CD (Cel) and 38 healthy controls (HC). Analysis of cell surface and/or intracellular antigens was performed in anti-CD3-treated PB mononuclear cells (PBMC) before and after treatment with recombinant IL-15 (rIL-15), and in IE and LP cellular suspensions prepared from duodenal biopsies pre-treated with/without rIL-15. RESULTS: A subpopulation of CD3+OX40+ T blasts was induced in Cel and HC by a 3days treatment of PBMC with anti-CD3 and decreased its size thereafter, regardless of the presence of rIL-15. However, the addition of rIL-15 to T blasts distinctively induced the survival of T cells with a regulatory phenotype that expresses OX40 antigen in Cel (p<0.05). Celiac patients showed higher frequencies of IFN-γ-producing CD3+CD30+ blasts before and after treatment with rIL-15 (p<0.05, vs. HC). IL-15 increased the frequencies of CD3+CD30+ LPL (HC: p<0.05, Cel: p<0.05) but not of CD3+OX40+ LPL, and CD30 or OX40 positive IEL. CONCLUSIONS: The distinctive control of OX40+ cells with a T regulatory phenotype mediated by the influence of IL-15 comes out as new function of this cytokine in the context of CD. The higher production of IFN-γ by a subpopulation of peripheral CD3+CD30+ cells contributes to the type I biased immune response.
Assuntos
Doença Celíaca/imunologia , Interleucina-15/imunologia , Antígeno Ki-1/imunologia , Ligante OX40/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Complexo CD3/imunologia , Duodeno/imunologia , Feminino , Humanos , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-15/uso terapêutico , Interleucina-4/biossíntese , Interleucina-4/imunologia , Mucosa Intestinal/imunologia , Masculino , Pessoa de Meia-Idade , Mucosa/citologia , Mucosa/imunologia , Proteínas Recombinantes/uso terapêutico , Adulto JovemRESUMO
Interleukin (IL)-15 and CD30 may be associated with the ongoing intestinal immunologic activation in celiac disease (CD). We studied duodenal biopsies and blood samples of patients with active CD (Cel) and controls in order to determine the regulatory role proposed for CD30(+) T cells in this Th1-driven disease and the potential influences of IL-15 on CD30 expression. We detected that a CD30(+) T-cell subpopulation persists longer in Cel after a 5 day incubation with anti-CD3 antibody than in controls (p = 0.0063). CD30 upregulation by IL-15 in T blasts was greater in Cel than in controls (p = 0.0062). At the mucosal compartment, the CD30 antigen was examined by immunohistochemistry and quantified on isolated lamina propria (LP) and epithelial T cells by flow cytometry. For Cel and controls, similar mean percentages of CD3(+)CD30(+) intraepithelial T cells (5.88 vs. 5.51, p = ns) and LP T cells (7.38 vs. 7.49, p = ns) were observed at baseline and after in vitro gliadin challenge of duodenal biopsy samples. Our study demonstrates the occurrence of potentially important alterations of the immune response at the peripheral compartment. Our findings also allow us to speculate that a negative effect of soluble mediators at the mucosal compartment might counteract the latent influence of IL-15 on CD30 expression precluding a more severe course of active CD.
Assuntos
Doença Celíaca/imunologia , Doença Celíaca/patologia , Regulação da Expressão Gênica , Interleucina-15/metabolismo , Antígeno Ki-1/metabolismo , Adulto , Idoso , Biópsia , Doença Celíaca/metabolismo , Duodeno/imunologia , Duodeno/metabolismo , Feminino , Humanos , Interleucina-15/genética , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Antígeno Ki-1/genética , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Adulto JovemRESUMO
BACKGROUND/AIMS: Celiac disease (CD) patients are affected in their quality of life (QoL). Our objectives were to assess differences in quality of life of patients according to the clinical presentation at diagnosis, and to determine the time-course impact of a gluten-free diet. PATIENTS/METHODS: We prospectively evaluated 132 newly diagnosed adult CD patients and 70 healthy controls using self-administered questionnaires: the Short Form-36 health survey, the Gastrointestinal Symptoms Rating Scale; the Beck Depression Inventory both, at diagnosis and at 3-, 6- and 12-months on treatment. RESULTS: At diagnosis, patients with classical symptoms (n=97) exhibited a significantly more pronounced alteration of all items of the three questionnaires than atypical/silent cases (n=35) (p<0.01 to <0.00001). Silent CD patients had even better baseline scores (p<0.05 to <0.00001). Treatment produced a substantial and rapid (3-month) improvement of most outcome measures in classical and atypical patients but not in asymptomatic cases. Both subgroups attained comparable final scores with no differences comparing strictly adherents with partially compliant. CONCLUSIONS: Atypical/silent celiac disease patients have a significantly better baseline quality of life than those with classical symptoms. Treatment induces a rapid and significant improvement in symptomatic cases but not in silent patients with all subgroups having similar 1-year scores comparable to healthy controls.
Assuntos
Doença Celíaca/dietoterapia , Doença Celíaca/diagnóstico , Qualidade de Vida , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Doença Celíaca/classificação , Dieta Livre de Glúten , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND/AIMS: Evidence of an increased bone fracture risk in coeliac disease is on debate. Our aim was to review systematically the current published information on fractures in coeliac disease and to perform a meta-analysis. METHODS: Case-control and cohort designs were identified by searching MEDLINE (1966-April 2007) and LILACS (1982-April 2007). Participants were adult coeliac disease patients of any sex and the outcome measure was the presence of any fracture. Studies were screened for inclusion by two authors who independently extracted the data. Methodological quality was assessed using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology Statement) recommendations. Data were analysed using the RevMan Analyses statistical package in Review Manager (version 4.2.8) and reported as pooled odds ratio using a random effect model. Heterogeneity was investigated (standard chi(2) test) and sensitivity analysis was performed based on the reported quality and design type. RESULTS: While 60 of 405 studies met the initial screening criteria, only 8 met inclusion criteria after detailed review. These studies evaluated a total of 20,955 coeliac disease patients having 1819 (8.7%) fractures and 96,777 controls with 5955 (6.1%) fractures (pooled odds ratio=1.43; 95% confidence interval 1.15-1.78) with considerable heterogeneity among studies (p<0.00001). CONCLUSIONS: Our meta-analysis confirms a significant association between bone fractures and coeliac disease. However, qualitative and quantitative differences among studies were evident. Further research is necessary to investigate the relevance of this heterogeneity.
Assuntos
Doença Celíaca/complicações , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Observação/métodos , Estudos de Coortes , Humanos , Osteoporose/complicações , Osteoporose/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND/AIMS: Our aims were to establish the clinical utility of assessing the intraepithelial lymphocyte (IEL) density in intestinal biopsies from a large series of individuals and to determine the best threshold discriminating celiac disease (CD) patients and controls in two populations with different pre-test prevalence. METHODS: We prospectively performed intestinal biopsy and CD-related serology in 349 subjects undergoing upper GI endoscopy. While 116 had symptoms suggestive of a small bowel disorder (high prevalence), 233 individuals were randomly selected from patients referred to endoscopy because upper GIsymptoms (low prevalence). Diagnosis of CD was based on the concordance of classical histological features and a positive CD serology. RESULTS: While 58 patients had a newly diagnosed CD (52 in the high and 6 in the low prevalence groups), 291 subjects did not meet diagnostic criteria of the disorder. Patients had a highly significant greater IEL density than controls (p < 0.00001). Based on the ROC curve, a count of 22.8 IEL/100 epithelial cells had the highest performance for diagnosing CD in the overall population and for subjects in the high pre-test probability subgroup and 22.5% was ,he best cut-off for those diagnosed in the low risk population (area under the curves: 0.979, 0.979 and 0.993, respectively). An abnormal CD serology confirmed the diagnosis of CD in all the four patients with counts below 22.8%. CONCLUSIONS: Our study confirms that an IEL density of 22.8% is an adequate threshold to discriminate CD patients and controls in individuals irrespective of the prevalence of the disorder.(AU)
Introducción: El recuento elevado de linfocitos intraepiteliales (LIEs) es un rasgo destacado aunque inespecífico de la enteropatía de la enfermedad celíaca (EC). Un recuento mayor a 40 LIEs/100 células epiteliales ha sido considerado por mucho tiempo esencial para el diagnóstico. Sin embargo, estudios recientes con escaso número de muestras han cuestionado este valor de corte. Objetivos: Determinar el rango normal de LIEs en biopsias intestinales y establecer su capacidad diagnóstica de EC en dos poblaciones con diferente prevalencia. Métodos: Realizamos prospectivamente biopsias de duodeno distal y serología para EC en 349 pacientesconsecutivos a quienes se les realizó una videoendoscopia digestiva alta. El grupo A consistió en 116 pacientes derivados a biopsia intestinal por síntomas sugestivos de malabsorción (considerados de alta prevalencia de EC) y el grupo B consistió en 233 pacientes randomizados entre quienes fueron derivados a endoscopía alta por síntomas gastrointestinales no sugestivos de EC (baja prevalencia de EC). El diagnóstico de EC se basó en criterios histológicos clásicos y serología positiva. Resultados: Cincuenta y ocho pacientes tuvieron EC (52 en el grupo de alto riesgo y 6 en el de baja prevalencia) y 291 individuos no tuvieron criterios de la enfermedad. Los pacientes tuvieron una densidad de LIEs significativamente mayor que los controles (p<0.00001). Basado en las curvas ROC, el conteo de 22.8 LIEs/100 células epiteliales tuvo la mejor sensibilidad y especificidad para el diagnóstico de EC en la población general y entre los sujetos con alta probabilidad y 22.5% fue el mejor valor de corte para la población de bajo riesgo (áreas bajo las curvas: 0.979, 0.979 y 0.993, respectivamente). Todos aquellos pacientes celíacos con recuento de LIEs por debajo de 22% (n=4), tuvieron serología positiva para EC. El clásico valor de 40% tuvo una sensibilidad del 55%. Conclusiones: Nuestro estudio confirma que una...(AU)
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença Celíaca/diagnóstico , Mucosa Intestinal/citologia , Biópsia , Estudos de Casos e Controles , Doença Celíaca/imunologia , Contagem de Linfócitos , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
BACKGROUND/AIMS: Our aims were to establish the clinical utility of assessing the intraepithelial lymphocyte (IEL) density in intestinal biopsies from a large series of individuals and to determine the best threshold discriminating celiac disease (CD) patients and controls in two populations with different pre-test prevalence. METHODS: We prospectively performed intestinal biopsy and CD-related serology in 349 subjects undergoing upper GI endoscopy. While 116 had symptoms suggestive of a small bowel disorder (high prevalence), 233 individuals were randomly selected from patients referred to endoscopy because upper GIsymptoms (low prevalence). Diagnosis of CD was based on the concordance of classical histological features and a positive CD serology. RESULTS: While 58 patients had a newly diagnosed CD (52 in the high and 6 in the low prevalence groups), 291 subjects did not meet diagnostic criteria of the disorder. Patients had a highly significant greater IEL density than controls (p < 0.00001). Based on the ROC curve, a count of 22.8 IEL/100 epithelial cells had the highest performance for diagnosing CD in the overall population and for subjects in the high pre-test probability subgroup and 22.5% was ,he best cut-off for those diagnosed in the low risk population (area under the curves: 0.979, 0.979 and 0.993, respectively). An abnormal CD serology confirmed the diagnosis of CD in all the four patients with counts below 22.8%. CONCLUSIONS: Our study confirms that an IEL density of 22.8% is an adequate threshold to discriminate CD patients and controls in individuals irrespective of the prevalence of the disorder.
Introducción: El recuento elevado de linfocitos intraepiteliales (LIEs) es un rasgo destacado aunque inespecífico de la enteropatía de la enfermedad celíaca (EC). Un recuento mayor a 40 LIEs/100 células epiteliales ha sido considerado por mucho tiempo esencial para el diagnóstico. Sin embargo, estudios recientes con escaso número de muestras han cuestionado este valor de corte. Objetivos: Determinar el rango normal de LIEs en biopsias intestinales y establecer su capacidad diagnóstica de EC en dos poblaciones con diferente prevalencia. Métodos: Realizamos prospectivamente biopsias de duodeno distal y serología para EC en 349 pacientesconsecutivos a quienes se les realizó una videoendoscopia digestiva alta. El grupo A consistió en 116 pacientes derivados a biopsia intestinal por síntomas sugestivos de malabsorción (considerados de alta prevalencia de EC) y el grupo B consistió en 233 pacientes randomizados entre quienes fueron derivados a endoscopía alta por síntomas gastrointestinales no sugestivos de EC (baja prevalencia de EC). El diagnóstico de EC se basó en criterios histológicos clásicos y serología positiva. Resultados: Cincuenta y ocho pacientes tuvieron EC (52 en el grupo de alto riesgo y 6 en el de baja prevalencia) y 291 individuos no tuvieron criterios de la enfermedad. Los pacientes tuvieron una densidad de LIEs significativamente mayor que los controles (p<0.00001). Basado en las curvas ROC, el conteo de 22.8 LIEs/100 células epiteliales tuvo la mejor sensibilidad y especificidad para el diagnóstico de EC en la población general y entre los sujetos con alta probabilidad y 22.5% fue el mejor valor de corte para la población de bajo riesgo (áreas bajo las curvas: 0.979, 0.979 y 0.993, respectivamente). Todos aquellos pacientes celíacos con recuento de LIEs por debajo de 22% (n=4), tuvieron serología positiva para EC. El clásico valor de 40% tuvo una sensibilidad del 55%. Conclusiones: Nuestro estudio confirma que una...
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Doença Celíaca/diagnóstico , Mucosa Intestinal/citologia , Biópsia , Contagem de Linfócitos , Curva ROC , Doença Celíaca/imunologia , Estudos Prospectivos , Estudos de Casos e Controles , Sensibilidade e Especificidade , Valor Preditivo dos TestesRESUMO
BACKGROUND: Diagnosis of Whipple's disease, a rare systemic infection affecting predominantly the small bowel, is based on the identification of the bacterium Tropheryma whipplei. AIMS: To make explicit diagnostic uncertainties in Whipple's disease through a decision analysis, considering two different clinical scenarios at presentation. METHODS: Using appropriate software, a decision tree estimated the consequences after testing different strategies for diagnosis of Whipple's disease. Probabilities and outcomes to determine the optimum expected value were based on MEDLINE search. RESULTS: In patients with clinically-predominant intestinal involvement, diagnostic strategies considering intestinal biopsy for histology (including appropriate staining) and the polymerase chain reaction testing for bacterial DNA were similarly effective. In case of failure of one procedure, the best sequential choice was a polymerase chain reaction analysis after a negative histology. Of the five strategies tested for cases with predominant focal neurological involvement, the stereotaxis cerebral biopsy evidenced the highest expected value. However, using quality-adjusted life-years considering the morbidity of methods, intestinal biopsy for PCR determination was the best choice. CONCLUSIONS: In patients with Whipple's disease having predominant digestive involvement, intestinal biopsies for histology should be indicated first and, if negative, a bacterial polymerase chain reaction determination should be the next option. Although the molecular polymerase chain reaction assessment of cerebral biopsies has the highest diagnostic yield in neurological Whipple's disease, its associated morbidity means that analyses of intestinal samples are more appropriate.
Assuntos
Técnicas de Apoio para a Decisão , Doença de Whipple/diagnóstico , Doenças do Sistema Nervoso Central/complicações , DNA Bacteriano/análise , Árvores de Decisões , Duodeno/patologia , Endoscopia Gastrointestinal/métodos , Humanos , Intestinos/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Sensibilidade e EspecificidadeRESUMO
Celiac disease (CD) is associated with decreased bone mineral mass. Its pathogenesis is multifactorial since both systemic and local mechanisms may play a role. Our objective was to determine whether single-nucleotide polymorphisms in genes encoding members of the interleukin-1 family are associated with bone damage measured by densitometry in a series of 71 adult CD patients assessed at diagnosis. When compared with non-carrier CD patients, carriers of allele T of the interleukin-1beta gene (IL1B-511T) had a significantly lower bone mass at the total skeleton level (p = 0.0484) and a greater prevalence of osteopenia/osteoporosis (p = 0.0102). To our knowledge, this is the first evidence on the association between a genetic predisposition and low bone mass in CD patients. This finding supports the postulated inflammation-associated bone loss pathogenesis as one of the causes of bone weakness in CD.
Assuntos
Doença Celíaca/complicações , Doença Celíaca/genética , Interleucina-1/genética , Osteoporose/etiologia , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIM: Smooth muscle antibody (SMA) specific for the protein actin, a major component of the cytoskeleton of epithelial cells, is one of the most prevalent non-organ specific autoantibodies in the serum of celiac disease (CD) patients. Our aim was to explore the clinical relevance of the presence of IgA type anti-actin antibody (AAA) and SMA in a series of patients with CD. METHODS: We evaluated frozen serum samples collected at diagnosis from 92 adult patients with CD and 52 control individuals in whom CD was excluded. Patients were re-evaluated a median time of 5 yr after treatment. IgA type AAA was detected using a modified commercial ELISA assay and IgA SMA was detected using indirect immunofluorescence on primate esophagus substrate. RESULTS: At diagnosis, samples from CD patients had significantly higher AAA values than controls (p<0.00001). While all active CD patients had serum AAA values over the cut-off for healthy controls, we observed a very significant reduction of these antibodies after treatment (p>0.0001). AAA had a highly significant correlation with both, tissue, transglutaminase (r=0.62) and antigliadin (r=0.60, p<0.00001) antibodies as well as the severity of the intestinal injury (p<0.05). SMA was detected in sera of 35 consecutive CD patients. At diagnosis, SMA positive patients had significantly higher values of AAA (p<0.0002), increased number of autoimmune disorders (p<0.04), delayed menarche (p<0.04), lower hemoglobin levels (p<0.01), increased fecal a-I antitrypsin clearance (p<0.01) and more severe diarrhea (p<0.06). We also detected a trend to more severe complications at follow-up (p=0.059). CONCLUSIONS: Based on our findings we suggest that the presence of increased IgA AAA serum levels is a highly sensitive marker of the disturbed architecture of intestinal epithelial cells of CD patients with a potential relevance to diagnosis and follow-up. The presence of SMA seems to define a distinct subset of CD patients with ...(AU)
Introduccion/objetivo: El anticuerpo anti-musculo liso (SMA) dirigido contra la proteína actina, un componente mayor del citoesqueleto de las células epiteliales, es el anticuerpo no-órgano específico más prevalente en enfermedad celíaca (EC). Nuestro objetivo fue explorar la importancia clínica de los anticuerpos anti-actina (AAA) y SMA en una serie de pacientes con EC. Métodos: Evaluamos 92 muestras serológicas de pacientes celíacos adultos recolectadas al momento del diagnóstico y la de 52 individuos controles no celíacos. Los pacientes fueron re-evaluados luego de un tiempo medio de 5 años en tratamiento. Evaluamos AAA tipoIgA mediante ELISA empleando un equipo commercial modificado y SMA IgA por inmunofluorescencia indirecta sobre sustrato de esófago de mono. Resultados: Al momento del diagnóstico, los pacientes celíacos tuvieron valores de AAA significativamente más elevados que los controles (p<0.00001). Todos los pacientes con EC activa presentaron niveles de AAA por encima del valor de corte determinado para el grupo control sano y se evidenció una reducción significativa de los nivelesluego del tratamiento (p>0.0001). Los AAA presentaron una correlación significativa con los anticuerpos anti-transglutaminasa tisular (r=0.62) y anti-gliadina (r=0.60) (p<0.00001), de igual modo que con la severidad del daño intestinal (p<0.05). Al momento del diagnóstico, se detectó SMA en el suero de 35 pacientes no controles. Los pacientes SMA positivos tuvieron valores significativamente mayores de AAA (p<0.002), un incremento del número de enfermedades autoinmunes asociadas (p<0.04), menarca tardía (p<0.04), niveles bajos de hemoglobina (p<0.01), incremento del clearance de a-1 antitripsina fecal (p<0.01) y mayor severidad de la diarrea (p<0.06).En ellos se evidenció una tendencia al desarrollo de complicaciones más severas durante el seguimiento (p=0.059). Conclusiones: Sugerimos que la presencia de un valor sérico aumentado de AAA tipo IgA...(AU)