Marianna Durilova

Impact of Anti–Tumor Necrosis Factor Alpha Antibodies Administered to Pregnant Women With Inflammatory Bowel Disease on Long-term Outcome of Exposed Children

Background:Prenatal exposure to anti–tumor necrosis factor &agr; (TNF-&agr;) antibodies seems to be safe for fetal development. Data on long-term outcome of exposed children are missing. Our aim was to assess long-term postnatal development of children exposed to anti–TNF-&agr; during pregnancy. Methods:Consecutive children aged ≥12 months exposed to anti-TNFs prenatally for maternal inflammatory bowel disease in 3 centers in the Czech Republic were enrolled. Data on psychomotor development, infections, antibiotics, vaccination, and allergy were retrospectively obtained from mothers, treating pediatricians, and childrens vaccination cards. Furthermore, standardized laboratory tests on humoral and cellular immunity were performed. Results:Twenty-five children exposed to biologicals were included (median age, 34 mo; range, 14–70 mo). All children had normal growth, and all but 1 had normal psychomotor development. Majority (80%) experienced at least 1 infection (mainly respiratory), and 60% of infants received antibiotics, 32% of those within the first year of life. Vaccination was undertaken according to vaccination protocol to 23 infants (92%). Fifteen children also had tuberculosis vaccination without serious complication. Immunological investigation was performed with 17 children (68%). Cellular immunity was normal in all infants, and 7 children had mild decrease in IgA and/or IgG immunoglobulins without clinical significance. All children had a detectable serologic response to vaccination. Conclusions:Exposure to anti–TNF-&agr; antibodies seems to be safe for growth and psychomotor development of children, although clinical significance of relatively high frequency of infections and antibiotic use among infants remains questionable because of the lack of a control group. Continuous follow-up of exposed children is absolutely warranted.

Switch from a dominant Th1-associated immune profile during the pre-diabetic phase in favour of a temporary increase of a Th3-associated and inflammatory immune profile at the onset of type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease dominated by loss of self‐tolerance resulting in depletion of the β‐cells. This study aims to confirm previous observations of a dominant T‐helper (Th)1‐like profile during the period close to onset of disease. Further, to follow the immune response from onset to 2 years duration, the study focused on spontaneous as well as autoantigen‐induced immune profile.

Disease activity is an important factor for indeterminate interferon-γ release assay results in children with inflammatory bowel disease.

Background: Interferon-&ggr; release assay (IGRA) is widely used for screening of latent tuberculosis (TB) before and during biological therapy (BT). An indeterminate result of IGRA represents a limitation in the management of inflammatory bowel disease (IBD). Data on factors influencing IGRA results are scarce in children. The aim of the study was to identify factors influencing IGRA results in children with IBD. Methods: Seventy-two children with IBD (59 Crohn disease, 11 ulcerative colitis, 2 IBD-unclassified) indicated for BT were tested for TB infection (history, TB skin test, chest radiograph, IGRA; QuantiFERON—TB Gold in tube [QFT]) and consecutively retested using QFT in 1-year intervals. Results: We recorded 165 results of QFT (3% positive, 87% negative, and 10% indeterminate results). During follow-up we identified 4 conversions of negative QFT to positivity (3%) and 4 reversions (4%). Patients with indeterminate results of QFT had significantly lower actual weight-for-height z score (P = 0.022), higher platelet count (P = 0.00017), and lower levels of serum albumin (P = 0.015) compared with patients with positive or negative QFT. Indeterminate QFT was associated with corticosteroid treatment, BT, and disease activity, but not with treatment by immunomodulators. In a subanalysis of patients with Crohn disease alone, Pediatric Crohns Disease Activity Index was identified as single independent risk factor for indeterminate results (P = 0.00037). Conclusions: Although corticosteroid treatment is traditionally considered to be the main risk factor for indeterminate results of IGRA, the disease activity of IBD has even more profound effects on the results.

Influence of Maternal Hyperglycaemia on Cord Blood Mononuclear Cells in Response to Diabetes‐associated Autoantigens

Perfect maternal diabetes compensation is crucial for the outcome of the baby. However, little is known how hyperglycaemia influences the specific immune response. Furthermore, babies of type 1 diabetes (T1D) mothers have less risk of development T1D than babies with a T1D father. This study aimed to analyze the effect of maternal hyperglycaemia on newborns with focus on the response to diabetes‐associated autoantigens. Populations: (1) Newborns of T1D mothers split into groups according to maternal diabetes compensation during the 3rd trimester: perfect (n = 15) or acceptable (n = 25) compensation. (2) newborns with T1D father (n = 12) (3) newborns with a mother treated for either gestational or type 2 diabetes (n = 10) (4) control newborns (n = 25). Spontaneous as well as diabetes‐associated autoantigen‐stimulated production of 23 cytokines and chemokines were tested using protein microarray. In addition, the influence of glucose on cytokine and chemokine responsiveness was analyzed in vitro. The study groups differed in their spontaneous as well as stimulated cytokine and chemokine spectra. A prominent Th1 response (high IFN‐gamma) from autoantigen stimulation was observed especially in babies of T1D fathers (P = 0.001) and also in mothers with perfect diabetes compensation during the 3rd trimester (P = 0.016) in comparison with control newborns. By contrast, cord blood mononuclear cells cultivated in vitro in high glucose concentration decreased the diabetogenic stimulated Th1 cytokine response. Maternal ‘sweet’ as well as ‘autoimmune environment’ may both lead to lower occurrence of T1D within their offspring. Further studies will reveal the exact immunological mechanism of this observation.

Is there any relationship between cytokine spectrum of breast milk and occurence of eosinophilic colitis

Aim:  The aim of our study was to analyse cytokine composition of human milk and its relationship to the development of eosinophilic colitis (EC).

Thromboelastometry as an Alternative Method for Coagulation Assessment in Pediatric Patients Undergoing Invasive Procedures: A Pilot Study

Introduction Standard coagulation tests (activated partial thromboplastin time [aPTT] and prothrombin time [PT]) are used for the assessment of coagulation profile in critically ill pediatric patients undergoing invasive interventions such as insertion of central venous catheter, tonsillectomy, laparotomy, etc. However, these tests do not reflect the profile of whole blood coagulation. Rotational thromboelastometry (ROTEM) as a point of care (POC) viscoelastic test may serve as an alternative method. Due to its ability to assess coagulation profile of the whole blood, it might yield normal results despite prolonged aPTT/PT results. The aim of this study was to find out if there was any severe bleeding during or after invasive procedures if ROTEM test was normal despite prolonged values of aPTT/PT in pediatric patients. Materials and Methods We retrospectively analyzed data for the years 2015 to 2017 for pediatric patients with prolonged values of aPTT or PT and normal ROTEM tests—internal thromboelastometry (INTEM) (assessing internal pathway of coagulation) and external thromboelastometry (EXTEM) (assessing external pathway of coagulation)—and we looked for severe bleeding during or after invasive procedures. Results In 26 pediatric patients (children from 2 months to 17 years old), we found that INTEM and EXTEM tests showed normal coagulation despite prolonged values of aPTT ratio with a median of 1.47 (minimum 1.04 and maximum 2.05), international normalized ratio with a median of 1.4 (minimum 0.99 and maximum 2.10), and PT ratio with a median of 1.30 (minimum 0.89 and maximum 2.11). In these patients, no severe bleeding was observed during interventions or postoperatively. Conclusion Our data support using thromboelastometry method as an alternative coagulation test for the assessment of coagulation profile in pediatric patients undergoing surgical or other invasive procedures, especially using it as a POC test. All invasive procedures in our study were performed without severe bleeding despite prolonged values of PT/aPTT with normal ROTEM results. It seems that ROTEM assessment of coagulation may lead to decreased administration of fresh frozen plasma and shorten time of patient preparation for intervention.

Development of High‐Sensitive ELISA Method for Detection of Adipophilin Levels in Human Colostrum and Breast Milk

To develop and validate high‐sensitive (hs) ELISA method for detection of adipophilin (adipose differentiation‐related protein, ADRP) in human breast milk (BM) and to analyze adipophilin levels in BM during 12 months of lactation.