The Covert Surge: Murine Bile Acid Levels Are Associated With Pruritus in Pediatric Autoimmune Sclerosing Cholangitis.

Objectives: The exact etiology of pruritus in chronic cholestasis is unknown. Pruritus intensity does not correlate with common biochemical indices and there is a lack of biomarkers guiding diagnosis and treatment. We explored profiles of bile acids (BA) and muricholic acids (MCA) as well as autotaxin (ATX) antigen levels as potential circulating biomarkers of pruritus in pediatric patients. Methods: In 27 pediatric cholestatic patients [autoimmune sclerosing cholangitis (ASC) n = 20 (with pruritus n = 6, without pruritus n = 14); progressive familial intrahepatic cholestasis (PFIC) n = 7 (with pruritus n = 5, without pruritus n = 2)] and 23 age-matched controls pruritus was assessed by a visual analog scale of pruritus (PVAS). We obtained profiles of serum human BA including MCA using a mass-spectrometry assay and ATX antigen levels with a commercial ELISA. Results: PFIC and ASC patients exhibited significantly higher BA-, and MCA levels, than healthy controls, but only PFIC patients showed elevated ATX antigen levels higher [median: 1,650 ng/ml, interquartile rang (IQR): 776.9-3,742] compared to controls (median: 315.9 ng/ml, IQR: 251.1-417.2; PFIC p = 0.0003). ASC patients with pruritus showed only a minor increase in total BA (tBA) levels (median: 76.5 µmol/L, IQR: 54.7-205), but strikingly higher T-conjugated BA (median: 16.4 µmol/L, IQR: 8.9-41.4) and total MCA (tMCA) (median: 1.15 µmol/L, IQR: 0.77-2.44) levels compared to ASC patients without pruritus (tBA median: 24.3 µmol/L, IQR: 16.2-80.8; p < 0.0408; T-conjugated BA median: 1.3 µmol/L, IQR: 0.8-4.9; p = 0.0023; tMCA median: 0.30 µmol/L, IQR: 0.13-0.64, p = 0.0033). BA/MCA profiles distinctly differed depending on presence/absence of pruritus. Different from PFIC patients, ATX antigen levels were not significantly elevated in ASC patients with (median: 665.8 ng/ml, IQR: 357.8-1,203) and without pruritus (median: 391.0 ng/ml, IQR: 283.2-485.6). In ASC patients, tBA, tMCA, and ATX antigen levels did not correlate with pruritus severity. Conclusion: Despite the same underlying disease, pediatric ASC patients with pruritus exhibit significantly altered BA profiles and MCA levels compared to ASC patients without pruritus. ATX antigen levels seem to have little diagnostic or prognostic meaning in ASC patients. An increased ATX activity alone seems not to be causal for pruritus genesis in ASC patients. Clinical Trial Registration: [www.drks.de], identifier [DRKS00026913].

Joint involvement, disease activity and quality of life in pediatric Crohn's disease - a cross-sectional study.

BACKGROUND: Few published data describe how joint involvement, the most prevalent extraintestinal manifestation, affects quality of life (QoL) of children with Crohn's disease (CD). Arthritis and arthralgia rates in pediatric CD patients are reportedly 3-24% and 17-22%, respectively, but studies on pre-emptive and systematic screening of joint involvement with detailed musculoskeletal rheumatological exam are lacking. More detailed data collection on joint involvement improves our understanding of how arthropathy relates to disease activity and QoL measured by the Pediatric CD Activity Index (PCDAI) and IMPACT-III questionnaire. Our study aims were to assess joint involvement in pediatric CD and correlate it with the PCDAI and IMPACT-III. METHODS: In this cross-sectional, observational study, a pediatric gastroenterologist assessed consecutively-seen pediatric CD patients at a tertiary care center. Patients were screened for prevalence of current and previous arthropathy, including arthritis, enthesitis and arthralgia. A single experienced pediatric rheumatologist evaluated detailed musculoskeletal history, joint status, and modified Juvenile Arthritis Multidimensional Assessment Reports (JAMAR). PCDAI, IMPACT-III, sacroiliac MRI, and HLA-B27 genetic testing were also completed. RESULTS: A total of 82 (male:female, 1.2:1; age, 13.7 ± 3.2 years) patients were involved in this study. Mean disease duration at time of study was 21.6 ± 21 months; eight of the patients were newly-diagnosed. Of the 82 patients, 29 (35%) had evidence of arthritis; for 24 of those, this was revealed by physical exam during cross-sectional screening, and by prior documentation for the remaining five patients. Joint examination confirmed active arthritis in 8/24 (33%), active enthesitis in 1/24 (4%), and evidence of previous arthritis in 15/24 (62.5%) patients. Hip (41%) and knee (38%) joints were most commonly affected. Cumulative incidence of arthralgia was 48% (39/82), and 46% (18/39) of those patients had only arthralgia without arthritis, usually affecting the knee. Axial involvement was present in 10/82 (12%) patients. Joint involvement correlated with more severe CD disease activity, specifically higher PCDAI and lower IMPACT-III scores, and increased requirement for infliximab treatment. Sacroiliitis and HLA-B27 positivity were insignificant factors in this cohort. CONCLUSIONS: When a rheumatologist performed the assessment, joint involvement in pediatric CD was more prevalent than previously reported, in this cross-sectional study. Arthritis was associated with more severe CD disease activity and lower QoL.

Importance of donor-specific antibodies in the long-term outcome of liver-transplanted children / A donorspecifikus antitestek szerepének vizsgálata a gyermekkori májtranszplantációk hosszú távú kimenetelében.

Összefoglaló. Bevezetés: A gyermekkori májtranszplantációk hosszú távú kimenetelének javítása érdekében az immunológiai mechanizmusok kerültek a kutatások középpontjába. A donorspecifikus antitesteknek (DSA-k) fontos szerepük van a graft túlélésében a szervtranszplantációk után, a májtranszplantáció esetén azonban ez még vitatott. Célkituzés: Tanulmányunk célja májtranszplantált gyermekeknél a DSA-k meghatározása, valamint a DSA-k jelenléte és a graft állapota közötti összefüggés vizsgálata volt. Módszer: A Semmelweis Egyetem I. Sz. Gyermekgyógyászati Klinikáján gondozott 54 májtranszplantált gyermek vérmintájából történt a humán leukocytaantigén (HLA) elleni antitestek meghatározása. Vizsgáltuk, hogy a laboratóriumi vérvizsgálat eredményei - szérumbilirubin (összes, direkt), alkalikus foszfatáz (ALP), transzaminázok, gamma-glutamil-transzferáz (GGT), immunglobulin-G (IgG) -, az aszpartát-aminotranszferáz/thrombocyta hányadosindex (APRI) és a 4 tényezon alapuló fibrosisindex (FIB4) tekintetében van-e eltérés a DSA-pozitív, illetve a HLA-immunizált betegek esetén a nem immunizált csoporthoz képest. Eredmények: A vizsgált paraméterekben nem találtunk szignifikáns különbségeket a DSA-pozitív, a HLA-immunizált és a nem immunizált betegek csoportjai között. Következtetés: Bár a jelen vizsgálatban nem volt szignifikáns különbség a vizsgált paraméterek esetén, de ez a kis esetszámból is adódhat. A DSA-knak a graftfibrosis kialakulásában való szerepe tisztázására több páciens vizsgálata szükséges, ezért megkezdtük az összes páciensnél a DSA- és HLA- (donor, recipiens) meghatározást, valamint ennek a klinikai gyakorlatunkba való beépítését. Orv Hetil. 2021; 162(47): 1897-1901. INTRODUCTION: To improve the long-term survival of liver-transplanted children, immunological mechanisms became the main interest of researchers. Donor-specific antibodies (DSAs) play a significant role in graft survival after solid organ transplantation, although their role in liver transplantation is controversial. OBJECTIVE: The aim of our study was to determine the presence of DSAs in liver-transplanted children and to examine their effect on graft's condition. METHOD: The determination of anti-human leukocyte antigen (HLA) antibodies was performed using the blood samples of 54 liver-transplanted children. We analysed the difference between the results of the laboratory blood examination - serum bilirubin (all, direct), alkaline-phosphatase (ALP), transaminases, gamma-glutamyl transferase (GGT), immunoglobulin-G (IgG) -, aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB4) according to DSA and HLA immunization. RESULTS: We did not find any significant difference in the examined parameters regarding DSA and HLA immunization. CONCLUSION: Although this study was not able to provide significant difference in the examined parameters, this can be explained with the low number of cases. To clarify the significance of DSA in graft fibrosis, we need a larger dataset. We started regular DSA and HLA (donor and recipient) determination during follow-up in liver-transplanted children. Orv Hetil. 2021; 162(47): 1897-1901.

Cardiovascular Risk Assessment in Pediatric Liver Transplant Patients.

OBJECTIVES: Cardiovascular (CV) diseases play a leading role in the mortality of adult liver transplant (LT) recipients. However, data regarding CV risk factors in children after LT remain sparse. The present study assessed the presence of CV risk factors and signs of CV impairment in LT children. METHODS: A total of 42 LT recipients (21 men, age 9.93 ±â€Š3.57 years) were studied. Body composition [body mass index standard deviation score, percentage of body fat (by bioimpedance analysis)], lipid profiles, glycemic control, blood pressure, and arterial stiffness [assessed by aortic pulse wave velocity (PWV)] were evaluated. The effect of different treatment modalities [tacrolimus (TAC) (n = 30) or cyclosporine (CyA) (n = 11)] was also analyzed. RESULTS: Almost 18% of children were overweight or obese. Patients on TAC had a significantly higher body fat mass and percentage of body fat compared with the CyA group (P < 0.02). Borderline to high lipid values were present in 40% of patients. Children on CyA had higher serum cholesterol levels compared to TAC (P < 0.004). Nineteen percent of patients had hypertension. Half of the patients had glomerular filtration rate values <90 mL/min/1.73 m, whereas PWV values were above the 95th percentile in 12%. CONCLUSIONS: Increased body fat, chronic kidney disease, high lipid content, hypertension, and increased arterial stiffness are already present and are in part related to the type of immunosuppression regimen in LT children >5 years following transplantation. Long-term follow-up is needed to evaluate their impact on CV health and survival.

[Solid organ transplantation in childhood]. / Szervtranszplantáció gyermekkorban.

Paediatric organ transplantation today is considered and accepted and widely available therapy in children with end-stage organ failure. It is important to know that in childhood, diseases leading to end-stage organ failure differ from those in adults. Beside this, in children there are different surgical and paediatric challenges before and after transplantation (size differences of the patient and donor organ, special and paediatric infections, different pharmacokinetics and pharmacodynamics of immunosuppressive drugs, noncompliance). However, paediatric organ transplantation in the last decades became a success story of the Hungarian health care owing to several working groups in Hungary and outside the country. Orv Hetil. 2018; 159(46): 1948-1956.

Altered activation of peripheral CD8+ T cells in pediatric Crohn's disease.

AIM: Although Crohn's disease (CD) is an extensively investigated autoimmune condition, knowledge on early phase activation of lymphocytes, especially CD8+ Tc cells is scarce. Our aim was to investigate the calcium influx characteristics of CD8+ cells upon activation as well as the expression and function of Kv1.3 and IKCa1 lymphocyte potassium channels. METHODS: We took peripheral blood from 12 healthy controls, 23 CD children on conventional therapy and 6 severe CD children before and after infliximab therapy. Intracellular calcium levels were monitored in CD8+ lymphocytes using flow cytometry. RESULTS: In CD treated with standard therapy calcium response during activation was elevated. This was not affected by the inhibition of Kv1.3 or IKCa1 potassium channels. After the switch to infliximab potassium channel function and expression of CD8+ lymphocytes were comparable to healthy controls in severe CD. CONCLUSION: Calcium handling of CD8+ lymphocytes is altered in pediatric CD, which is normalized by infliximab therapy.

Altered calcium influx of peripheral Th2 cells in pediatric Crohn's disease: infliximab may normalize activation patterns.

OBJECTIVE: Crohn's disease is a chronic inflammation of the gastrointestinal tract with an abnormal immune phenotype. We investigated how intracellular calcium kinetics of Th1 and Th2 lymphocytes alter upon specific inhibition of Kv1.3 and IKCa1 channels in pediatric Crohn's disease. STUDY DESIGN: Blood was taken from 12 healthy and 29 Crohn's disease children. Of those, 6 were switched to infliximab and re-sampled after the 4th infliximab treatment. Intracellular calcium levels were monitored using flow cytometry in the presence or absence of specific inhibitors of Kv1.3 and IKCa1 potassium channels. RESULTS: In Crohn's disease treated with standard therapy, calcium response during activation was higher than normal in Th2 cells. This was normalized in vitro by inhibition of Kv1.3 or IKCa1 potassium channels. After the switch to infliximab, potassium channel function and expression in Th2 lymphocytes were comparable to those in Th1 cells. CONCLUSION: These results may indicate that potassium channels are potential immune modulatory targets in Crohn's disease.

Role of Altered Expression of miR-146a, miR-155, and miR-122 in Pediatric Patients with Inflammatory Bowel Disease.

BACKGROUND: Evidence suggests the central role of tumor necrosis factor (TNF)-α in the pathomechanism of inflammatory bowel disease (IBD); however, its effect on epigenetic factors, including small non-coding microRNAs (miRs), is less known. Our present aim was the comparative investigation of the expression of TNF-α and immune response-related miRs in children with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Fresh-frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) biopsies were used to analyze the expression of miR-146a, -155, -122, and TNF-α by real-time reverse transcription polymerase chain reaction in macroscopically inflamed (CD: 12 FFPE and 24 FF; UC: 10 FF) and intact (CD: 12 FFPE; 14 FF) colonic biopsies of children with IBD and controls (16 FFPE; 23 FF). The expression of miR-146a, -155, and -122 was also determined in TNF-α-treated HT-29 colonic epithelial cells. RESULTS: Increased expression of TNF-α was observed in the colonic mucosa of children with CD and UC in comparison with controls. Expression of miR-146a and -155 was higher in the inflamed mucosa of children with CD and UC than in the intact mucosa. Expression of miR-122 elevated in the macroscopically intact colonic regions of CD compared with controls and patients with UC. In HT-29 cells, TNF-α treatment increased the expression of miR-146a and -155, but not that of miR-122. CONCLUSIONS: Our results showed altered expression of miR-146a, -155, and -122 in the colonic mucosa of children with IBD and in TNF-α-treated colonic epithelial cells. Our data suggest the TNF-α-related involvement of these miRs in the pathogenesis of IBD.

Seasonal variability of vitamin D and bone metabolism in infliximab-treated paediatric Crohn's disease.

BACKGROUND: Paediatric Crohn's disease patients suffer from several complications, including low bone mineral density and inadequate serum levels of 25-hydroxy vitamin D. AIMS: The aim of this prospective study was to address the effect of infliximab therapy on bone metabolism, bone mineral density and vitamin D homeostasis. The seasonal variability of serum vitamin D levels in relation to infliximab treatment was also analysed. METHODS: Serum osteocalcin and beta-crosslaps (markers of bone metabolism), seasonal variability of vitamin D, and bone mineral density were assessed and followed throughout the yearlong treatment regimen of infliximab in 50 consecutive paediatric patients with moderate to severe Crohn's disease. RESULTS: Bone forming osteocalcin levels were significantly (p<0.001) increased during infliximab therapy. In contrast, no significant changes in beta-crosslaps and vitamin D levels were observed. Vitamin D levels were significantly different when the summer and winter periods were compared at week 0 (p=0.039); however, this difference was not detected after one year of infliximab therapy. Despite the beneficial clinical effect of infliximab, there was no significant change in bone mineral density Z-scores after one year of treatment. CONCLUSION: Infliximab may beneficially affect bone homeostasis. Moreover, seasonal variability in vitamin D levels observed prior to initiation of infliximab treatment was diminished after one year of treatment.

Peroxisome proliferator-activated receptor-γ and thymic stromal lymphopoietin are involved in the pathophysiology of childhood coeliac disease.

Celiac disease (CD) is a chronic autoimmune enteropathy caused by exposure to dietary gluten in genetically predisposed individuals. The transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) was shown to exert protective effects in several immune-mediated disorders. Activation of PPARγ suppressed the expression of thymic stromal lymphopoietin (TSLP), an inducer of proinflammatory cytokines. Since the role of TSLP in gluten-sensitive enteropathy is completely unknown, we investigated the involvement of TSLP and its regulator PPARγ in childhood CD. We collected duodenal biopsy specimens from 19 children with newly diagnosed CD, 6 children with treated CD (gluten-free diet, GFD), and 10 controls. Expression of mRNA and protein levels of PPARγ, TSLP, and TSLP receptor were determined by real-time RT-PCR and Western blot, respectively. Duodenal localization of PPARγ and TSLP was studied by immunohistochemistry. In duodenal mucosa of children with CD, the amount of PPARγ was significantly lower and simultaneously that of TSLP significantly higher compared to controls (p < 0.05). In GFD-treated patients, the levels of PPARγ mRNA and protein were significantly higher while that of TSLP markedly lower compared to newly diagnosed CD (p < 0.05). Immunohistochemistry revealed PPARγ and TSLP expression in lamina propria immune cells and in enterocytes. Low expression of PPARγ and high expression of TSLP in the duodenal mucosa of children with newly diagnosed CD suggest that they are involved in the pathophysiology of CD. We hypothesize that PPARγ may be an inhibitory regulator of TSLP-stimulated inflammatory processes in CD.

[Successful autologous haematopoietic stem cell transplantation in severe, therapy-resistant childhood Crohn's disease. Report on the first case in Hungary]. / Sikeres autológ haemopoeticus ossejt-transzplantáció gyermekkori, súlyos, terápiarezisztens Crohn-betegségben. Az elso hazai beteg esetének ismertetése.

The biological therapy of Crohn's disease, such as infliximab is a powerful approach in the therapy of inflammatory bowel diseases. However, in some patients with aggressive disease course, even a combined immunosuppressive therapy will not result in permanent remission. Hematopoietic stem cell transplantation has emerged as a new potential therapeutic tool for inflammatory bowel diseases. The authors report the case of a 15-year-old boy with severe Crohn's disease resistant to combined immunosuppressive therapy. After a 3-years course of unsuccessful conventional therapy including infliximab, autologous hematopoietic stem cell transplantation was performed which resulted in a complete remission. One year after transplantation the patient has relapsed, but he could be treated effectively with conventional therapy regiments. To the best of knowledge of the authors, this is the first report in Hungary presenting hematopoietic stem cell therapy in patient with severe Crohn's disease.

[Genetic and epigenetic aspects of celiac disease]. / A coeliakia genetikai és epigenetikai vonatkozásai.

Genetic background of coeliac disease has been subjects to intensive research since decades. However, only results of HLA phenotyping have been taken over to routine clinical practice. Meanwhile, data on the role of epigenetical factors in the manifestation of diseases have been emerging. In coeliac disease, there are several questions both in the fields of genetics and epigenetics yet to be answered. In this review, a cross section of current knowledge on these issues is presented with special interest regarding the future clinical applications.

Autoregressive cross-lagged models of IMPACT-III and Pediatric Crohn's Disease Activity Indexes during one year infliximab therapy in pediatric patients with Crohn's disease.

BACKGROUND: Quality of life (QoL) is an important outcome measure in the evaluation of therapies for inflammatory bowel disease. The primary aim of this study was to determine the effect of one year infliximab treatment on QoL and clinical parameters in pediatric patients with Crohn's diseases (CD). METHODS: Our prospective study involved 51 children with conventional therapy resistant, severe CD (mean age: 15.25years, range: 11-18years). Infliximab was given according to the protocol (5mg/kg, at weeks 0, 2, 6 and every 8weeks). During the infliximab courses QoL of patients was evaluated by IMPACT-III questionnaire at weeks 0, 6, 30 and 53. At the same time, the Pediatric Crohn's Disease Activity Index (PCDAI) score was calculated. Moreover, serum C-reactive protein (CRP), serum platelets and serum albumin were followed up. Auto-regressive, cross-lagged models were used to assess relation between QoL and the clinical parameters. RESULTS: The initial IMPACT-III scores [median, percentile 25-75 (pc 25-75) at week 0: 115, 102.5-130.25] increased significantly (p<0.001) following infliximab therapy at week 54 (median: 141.5, 124.5-153.75). Clinical and laboratory parameters also improved significantly (p<0.001). Auto-regressive regression coefficients (ß value) were significant between each variable over time. The strongest cross-lagged relations were observed between IMPACT-III and serum albumin, IMPACT-III and platelets. Reliability test of IMPACT-III revealed an excellent level of internal consistency (Cronbach's alpha=0.931). CONCLUSION: Infliximab treatment has beneficial clinical effect which is confirmed by decrease of PCDAI and increase of IMPACT-III. Autoregressive regression analysis showed regression relation between IMPACT-III and PCDAI and laboratory parameters.

Incidence, Paris classification, and follow-up in a nationwide incident cohort of pediatric patients with inflammatory bowel disease.

OBJECTIVES: The aim of the study was to evaluate the incidence, baseline disease characteristics, and disease location based on the Paris classification in pediatric inflammatory bowel disease (IBD) in the Hungarian nationwide inception cohort. In addition, 1-year follow-up with therapy was analyzed. METHODS: From January 1, 2007 to December 31, 2009, newly diagnosed pediatric patients with IBD were prospectively registered. Twenty-seven pediatric gastroenterology centers participated in the data collection ensuring the data from the whole country. Newly diagnosed patients with IBD younger than 18 years were reported. Disease location was classified according to the Paris classification. RESULTS: A total of 420 patients were identified. The incidence rate of pediatric IBD was 7.48/105 (95% confidence interval [CI] 6.34/105-8.83/105). The incidence for Crohn disease (CD) was 4.72/105 (95% CI 3.82-5.79), for ulcerative colitis (UC) 2.32/105 (95% CI 1.71-3.09), and for IBD-unclassified 0.45/105 (95% CI 0.22-0.84). Most common location in CD was L3 (58.7%); typical upper gastrointestinal abnormalities (ulcer, erosion and aphthous lesion) were observed in 29.9%. Extensive colitis in patients with UC (E4, proximal to hepatic flexure) was the most common disease phenotype (57%), whereas only 5% of children had proctitis. A total of 18.6% of patients had ever severe disease (S1). Frequency of azathioprine administration at diagnosis was 29.5% in patients with CD, and this rate increased to 54.6% (130/238) at 1-year follow-up. In UC, only 3.3% received azathioprine initially, and this rate elevated to 22.5% (25/111). Use of corticosteroid decreased from 50% to 15.3% in patients with UC. Rate of bowel resection in patients with CD during the first year of follow-up was 5%. CONCLUSIONS: The incidence of pediatric IBD in Hungary was among the higher range reported. This is the first large, nationwide incident cohort analyzed according to the Paris classification, which is a useful tool to determine the characteristic pediatric CD phenotype.

Low mannose-binding lectin (MBL) is associated with paediatric inflammatory bowel diseases and ileal involvement in patients with Crohn disease.

BACKGROUND: Mannose-binding lectin (MBL) is a pattern-recognition molecule of the innate immune system and may be involved in the pathogenesis of inflammatory bowel disease (IBD). Our aim was to assess the prevalence of MBL deficiency in a cohort of patients with paediatric-onset IBD and study whether it is associated with the clinical manifestations, serum antibody formation, or genetic factors. METHODS: This prospective study included 159 paediatric patients (mean age: 14.0 years) with IBD [107 patients with Crohn disease (CD) and 52 patients with ulcerative colitis (UC)]. Furthermore, 95 controls were investigated. Serum samples were determined for MBL by enzyme-linked immunosorbent assay (ELISA) and for serologic markers [autoantibodies against Saccharomyces cerevisiae (ASCA) and perinuclear components of neutrophils (pANCA)] by indirect immunofluorescent assay. NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The MBL serum concentration was significantly lower in IBD patients(both with CD and UC) compared to controls (IBD, p=0.007, CD, p=0.04, UC p=0.004). Prevalence of low MBL level (<500 ng/mL) was significantly higher in both CD and UC groups compared to controls (p=0.002 and p=0.006). Furthermore, low MBL level was associated with isolated ileal involvement (p=0.01) and MBL deficiency (<100 ng/mL) with male gender (p=0.004) in patients with CD. We failed to confirm any correlation between MBL deficiency and serum autoantibodies or NOD2/CARD15 variants. CONCLUSIONS: Our results suggest that low MBL associated with paediatric-onset IBD and ileal CD may be considered an additional marker of the IBD pathogenesis.

Pancreatic autoantibodies and autoantibodies against goblet cells in pediatric patients with inflammatory bowel disease.

BACKGROUND: Significance of pancreatic autoantibodies determined by using exocrine pancreas (PAB) and antibodies against recombinant pancreas antigen (rPAB), as well as the importance of autoantibodies against goblet cells (GAB), is not known in pediatric patients with inflammatory bowel disease (IBD). Our aim was to determine the complex analysis of PAB, rPAB, GAB, antibodies against Saccharomyces cerevisiae, and perinuclear components of neutrophils in pediatric patients with IBD. Moreover, association with NOD2/CARD15 and disease phenotype was determined. METHODS: A total of 152 pediatric patients (median age 13.9 years) with IBD (103 patients with Crohn disease [CD] and 49 patients with ulcerative colitis [UC]) and 104 controls were included. Serum autoantibodies were determined by indirect immunofluorescence assay. NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism. RESULTS: The presence of PAB and rPAB was significantly higher in CD (34% and 35.9%) and in UC (20.4% and 24.5%) compared with pediatric control cohort (0% and 0%, P<0.0001). In addition, GAB positivity was significantly increased in patients with UC in comparison with CD and controls, respectively (UC, 12.2%; CD, 1.9%; controls, 1.9%; P=0.02). Specificity of PAB and rPAB was 100%; however, sensitivity was low. The combination of PAB and/or antibodies against Saccharomyces cerevisiae/perinuclear components of neutrophils improved the sensitivity of serological markers in CD (87.4%) and in UC (79.6%); specificities were 89.3% and 93.2%, respectively. Pancreatic autoantibodies (PAB, rPAB) and GAB were not related to clinical presentation, medical therapy, or need for surgery in CD or in UC. CONCLUSIONS: Pancreatic autoantibodies and GAB were specific for IBD, but the sensitivity was limited as well because there was lack of correlation with clinical phenotype. Combinations of these antibodies have shown increased sensitivity; therefore, it may be recommended in the diagnostic procedure of IBD.

Diagnostic yield of upper endoscopy in paediatric patients with Crohn's disease and ulcerative colitis. Subanalysis of the HUPIR registry.

BACKGROUND, AIMS: According to Porto Criteria upper gastrointestinal (UGI) endoscopy is recommended in patients with suspected inflammatory bowel disease (IBD). Nevertheless, previous studies revealed frequent involvement of UGI tract even in patients with ulcerative colitis (UC). The aim of the present study was to determine the diagnostic role of esophagogastroduodenoscopy (EGD) and assess the prevalence and different aspects of UGI involvement in children registered in the Hungarian Pediatric IBD Registry (HUPIR) from 1st of January 2007 to 31th of December 2009. METHODS: Twenty seven institutes provided prospective follow-up data about newly diagnosed IBD patients to HUPIR. The registry was based on detailed questionnaire (76 parameters) involving anamnestic data, laboratory findings, activity indexes, diagnostic procedures, endoscopic examinations (EGD and ileocolonoscopy), and histological data. Localization and phenotype of disease were based on the Montreal classification criteria. RESULTS: During the 3-year period 420 children were diagnosed with IBD, 265 (63%) of them had Crohn's disease (CD), 130 (31%) UC, and 25 (6%) IBD-unclassified (IBD-U). The mean age at diagnosis was 13.2 years (range: 1.2-18 years). EGD was performed in 237 patients (56%), in most cases in patients suffering from CD. Macroscopic lesions on EGD were noted in 64% of patients with CD and 40% of children with UC. Characteristic lesions for CD (ulcer, erosion, aphthous lesion, and granuloma) were noted in 31% of CD patients, however, EGD helped to establish the final diagnosis in 9% of CD patients (diagnostic yield, 9%). CONCLUSIONS: There was a high frequency of UGI involvement in children with CD and UC. One third of CD patients showed significant lesions at upper endoscopy and one patient out of ten had real diagnostic help from EGD.

[Analysis of infliximab treated pediatric patients with Crohn disease in Hungary]. / Crohn-beteg gyermekek infliximabkezelésének kezdeti tapasztalatai hazánkban.

Infliximab, the chimeric antibody to tumor necrosis factor-alpha, is indicated for medically refractory pediatric Crohn disease. Aim of our study was to examine the efficacy and side effects of infliximab therapy in Hungarian pediatric patients with Crohn disease since the authorisation of medicine for children to 31.12.2008. 23 children with refractory Crohn disease received infliximab during this period. Induction therapy with 5 mg/kg infliximab at weeks 0, 2, and 6 was introduced. 18 patients (81.8%) achieved clinical response, and 13 patients (59.1%) were in remission at the 6th week of the observation period. The evaluation was based on data of 22 children. Fistula closure rate was 70% at the at the 6th week. Two patients had acute infusion reaction, one had severe anaphilactic reaction after infliximab infusion. Chronic side effects were also observed in three cases. In our study infliximab induction therapy was effective in most pediatric patients with therapy refractory Crohn disease.

[Adalimumab treatment in infliximab-resistant pediatric patient with Crohn's disease]. / Infliximab-rezisztens Crohn-beteg gyermek adalimumab-kezelése.

Treatment with the chimeric monoclonal antibody (infliximab) is highly effective in refractory and fistulising Crohn's disease, nevertheless, infliximab resistance may occur. Authors report a 12-year-old boy with infliximab refractory luminal Crohn's disease including 3 active perianal fistulas. The patient was treated successfully with adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody. After 10 weeks of therapy, the previously high activity index returned to normal and the fistulas were closed. Quality of life using validated questionnaire improved significantly also. Adalimumab might be a suitable therapy even in pediatric Crohn's disease patients with infliximab resistance.