Evaluation of HLA-DQ2/DQ8 genotype in patients with celiac disease hospitalised in 2012 at the Department of Paediatrics.

INTRODUCTION: Celiac disease (CD) is a permanent intolerance to gluten that occurs in genetically predisposed individuals and leads to small intestinal mucosa damage. According to ESPGHAN guidelines from 2012, CD can be diagnosed in a patient with characteristic clinical symptoms, in whom, anti-tissue transglutaminase antibodies (> 10 times the upper limit) are found, endomysial antibodies (EMA) is confirmed and a positive genetic test is obtained. In these conditions no small-bowel biopsies are required. AIM: Evaluation of the presence of HLA-DQ2 and HLA-DQ8 haplotypes in children with previously diagnosed CD, hospitalised in 2012 at the Department of Paediatrics and Immunology and/or the Gastroenterological Outpatient Clinic, and their relatives. MATERIAL AND METHODS: Blood samples of 22 subjects, including 9 children with CD diagnosed on the basis of clinical symptoms, serological investigations and small-intestine biopsy, 7 diagnosed on the basis of clinical symptoms and serological investigations, 2 with the suspicion of CD on the basis of clinical symptoms and 4 relatives of a child with CD. METHODS: HLA-DQ2/DQ8 test, automatic evaluation by EUROArrayScan. RESULTS: The presence of HLA-DQ2 and/or HLA-DQ8 genotype was confirmed in 16 children with CD diagnosed on the basis of clinical symptoms and serological tests with/without intestinal biopsy, in 2 with the suspicion of CD and in 1 relative of a celiac child. CONCLUSIONS: The evaluation of HLA-DQ2/DQ8 haplotype confirms the genetic predisposition to CD in subjects with the disease diagnosed previously on the basis of clinical symptoms, serological tests or intestinal biopsy. Genetic testing is particularly indicated for the diagnosis of CD in infants consuming gluten for a short time and in small amounts.

[Intravenously applied immunoglobulin in systemic, autoimmune and vasculitis diseases in children]. / Preparaty immunoglobulin w leczeniu chorób ukladowych o podlozu autoimmunizacyjnym i zapaleniach naczyn u dzieci.

Intravenous immunoglobulin (IVIG) have been widely used in clinical practice for more than 35 years. Their specificity and diversity and their relative safety make them potent therapy in antibody deficiencies, certain infections and several autoimmune and inflammatory disorders. IVIG is a biological drug that is used routinely for idiopathic thrombocytopenic purpura, Kawasaki disease, and Guillain-Barré syndrome. Therapeutic approaches for autoimmune diseases are primarily based on suppressive measures that down regulate an over productive immune system. IVIG efficacy has been established in many clinical trials for various autoimmune diseases, vasculitis and neuroimmunological, dermatological and hematological disorders. Despite the evidence of efficacy, there are no generally accepted therapeutic guidelines, the dosage and timing of IVIG therapy, and questions of costs/benefits ratio still remain insufficiently documented and multicentric controlled clinical trials are necessary. Most available evidence for a benefit for IVIG in children comes from uncontrolled open series or case reports.

[Alterations of metalloproteinases and their inhibitors concentrations in peripheral blood in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass]. / Zmiany stezen metaloproteinaz i ich inhibitorów w krwi obwodowej dzieci z wrodzona wada serca poddanych zabiegowi kardiochirurgicznemu z uzyciem krazenia pozaustrojowego.

Cardiac surgery with cardiopulmonary bypass (CPB) in children with congenital heart disease induces neutrophil activation, degranulation and systemic inflammatory response. Matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) are enzymes involved in degranulation and leukocyte extravasation. These are secreted as a pro-enzyme in response to several inflammatory mediators and are inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2). To explore metalloproteinase activation during cardiac surgery we investigated MMP-9, MMP-2, TIMP-1 and TIPM-2 levels in young children during and after surgery. We measured the dynamics of these enzyme concentrations in peripheral blood. Additionally we measured CD11b and CD66b molecule expression on neutrophils. These investigations were carried out in 39 children, aged 5-38 months who were undergoing cardiacsurgery with cardiopulmonary bypass (CPB). Serum concentrations of MMPs and their inhibitors, CD11b and CD66b expression on neutrophils were sequentially measured before induction of anesthesia, at the initiation of CPB, after 30 minutes of CPB, at the end of CPB, 4 and 48 hours after CPB. MMP-9 concentration increased at the end of CPB and remained elevated for a period of 48 hours. The concentration of MMP-9 detected at the end of CPB positively correlated with time of CPB (r=0.68, p=0.0045). TIMP-1 concentration decreased significantly after 30 minutes of CPB, remained lowered to the end of CPB, and returned to the start of CPB level after 48 hours. CD11b and CD66b expression on neutrophils increased at the initiation of CPB. Our data confirm that MMPs play an important role in inflammatory complications after cardiac surgery in children. These findings suggest that kinetics of MMPs concentrations in serum after cardiac surgery appear to depend on many factors. We demonstrated the link between CPB duration and the MMP-9 concentration. Future studies will determine whether inhibition of MMPs activity diminishes morbidity in children after cardiac surgery.

Proteolytic and cytokine balance abnormalities in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) in children with congenital heart disease induces a systemic inflammatory response. This inflammatory response is thought to be produced by exposing patients to proinflammatory factors. AIM: To explore the role of cytokines and proteolytic enzymes in inflammatory complications after cardiac surgery in children. METHODS: We investigated the dynamics of concentrations of IL-6, IL-8 and IL-10, and metalloproteinases (MMPs) MMP-2 and MMP-9, and their inhibitors - tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2. These investigations were carried out in 28 children, aged 4-34 months, who underwent a cardiac operation with CPB. Serum concentrations of proteins were sequentially measured before induction of anaesthesia, at the initiation of CPB, after 30 minutes of CPB, at the end of CPB, and 4 and 48 hours after CPB. RESULTS: The serum levels of IL-6 increased dramatically 4 hours after CPB compared with the level before anaesthesia (141.83+/-25.49 vs. 10.68+/-5.01 ng/ml, p=0.00004) and correlated with duration of CPB (r=0.74, p=0.00028). The serum levels of IL-8 increased 4 hours after CPB compared with the level before anaesthesia (267.1+/-41.3 vs. 8.5+/-6.3 ng/ml, p=0.00002). A significant increase of IL-10 concentration at the end of surgery and 4 hours after CPB was detected (95.12+/-23.57 vs. 10.34+/-6.45 ng/ml, p=0.000004 and 59.41+/-21.4 vs. 10.34+/-6.45 ng/ml, p=0.00004, respectively ). The MMP-9 concentration increased at the end of CPB and remained elevated for a period of 48 hours (44.40+/-13.95 vs. 19.53+/-7.58, p=0.000004 and 38.97+/-10.76 vs. 19.53+/-7.58, p=0.00004, respectively). The concentration of MMP-9 detected at the end of CPB positively correlated with duration of CPB (r=0.68, p=0.0045). The TIMP-1 concentration decreased significantly after 30 minutes of CPB, and remained lowered to the end of CPB (respectively 52.68+/-17.72 vs. 83.29+/-17.06 ng/ml, p=0.000006 and 34.94+/-10.58 vs. 83.29+/-17.06 ng/ml, p=0.00004,respectively). CONCLUSIONS: Cardiac surgery causes an increase of IL-6 and IL-8 concentrations in peripheral blood 4 hours after CPB termination. The concentration of anti-inflammatory IL-10 cytokine increases immediately after the end of CPB. We showed an increase of the MMP-2 and MMP-9 concentrations during and after CPB and simultaneous decrease of TIMP-1 inhibitor. We demonstrated a link between CPB duration and IL-6 and MMP-9 concentrations.

[The 22q11.2 deletion syndrome: immunological questions]. / Zespól mikrodelecji 22q11.2--zagadnienia immunologiczne.

The 22q11.2 deletion syndrome occurs in approximately 1 of 3000-5000 children. This is a congenital disorder characterized by facial dysmorphic features, cardiac defects, thymic hypoplasia, cleft palate, hypoparathyroidism, and psychiatric disorders. Patients generally exhibit a mild to moderate decrement in T-cell numbers with preservation of T-cell function. We describe advances in understanding the genetic basis of this syndrome, its clinical manifestations, and new information on immunodeficiences in this syndrome.

[Alterations of procalcitonin and interleukin 6 after cardiopulmonary bypass in children with congenital heart disease]. / Zmiany stezen prokalcytoniny i interleukiny 6 u dzieci z wrodzonq wadq serca podczas zabiegu kardiochirurgicznego i po jego zakonczeniu.

UNLABELLED: Cardiac surgery induces systemic inflammatory response that may have been implicated the postoperative organ dysfunction. This inflammatory response is thought to be produced by exposing patients to proinflammatory factors. The aim of our study was to investigate alterations in procalcitonin (PCT) concentration in peripheral blood in children as the potential early indicator of complications occurring during and after surgery in extracorporeal circulation. Additionally, we evaluated the perioperative time course of IL-6. MATERIAL AND METHODS: The investigations were carried out in 21 children undergoing cardiac operation with cardiopulmonary bypass (CPB). Serum concentrations of PCT and IL-6 were sequentially measured before induction of anesthesia, at the initiation of CPB, at the end of CPB, and 24 hours, and 72 hours after CPB. RESULTS: There was no significant PCT-elevation at all 5 times of measurement. Levels of IL-6 increased significantly after surgery, and remained elevated for up to 1 day. Peak values correlated with the duration of CPB (r=0.68, p=0.0006). CONCLUSIONS: We conclude, that cardiac surgery with CPB did not have any influence on the secretion of PCT in children. These results suggest that IL-6 was more effective than PCT to monitor patients with a favorable outcome.