Dose optimisation for Loss of Response to Vedolizumab- Pharmacokinetics and Immune Mechanisms.

BACKGROUND: Real life data regarding pharmacokinetics of vedolizumab in patients needing dose optimisation are scarce. We set to examine whether pre-optimisation vedolizumab levels associate with therapy outcomes and which mechanisms explain the associations. METHODS: A multicentre observational study assessed the outcome of dose increase in association with pre-escalation levels in vedolizumab-treated patients. SubsequentIy, α4ß7 occupancy on peripheral blood [PB] and intestinal lamina propria [LP] tissues was investigated on various cellular subsets in patients undergoing lower endoscopy on infusion day. Cellular localisation of vedolizumab-bound α4ß7 and effects on M1 and M2 macrophages were also explored. RESULTS: A total of 161 inflammatory bowel disease [IBD] patients were included. Among 129/161 patients intensified during maintenance [Week 14 onward], pre-intensification trough levels were comparable or higher among those subsequently attaining post-optimisation clinical, biomarker, and endoscopic remission, compared with non-remitting patients [p = 0.09, 0.25, 0.04, respectively]. Similar results were demonstrated for those dose-optimised during induction [Week 6, n = 32]. In the immune sub-study [n = 43], free α4ß7 receptors at trough were similarly low among patients with/without mucosal healing, on PB T cells [p = 0.15], LP T cells [p = 0.88], and on PB eosinophils [p = 0.08]. Integrin receptors on M1 and M2 macrophages were also saturated by low levels of vedolizumab and anti-inflammatory cytokine secretion was not increased. Co-localisation and dissociation experiments demonstrated membranal α4ß7 receptors of two origins: non-internalised and newly generated α4ß7, but re-binding was still complete at very low concentrations. CONCLUSIONS: These results do not support pharmacokinetics as the mechanism responsible for loss of response to vedolizumab, nor do they support a need for higher drug concentration to enhance vedolizumab's immune effects. Higher pre-escalation levels may indicate less clearance [less severe disease] and higher likelihood of subsequent re-gained response, regardless of therapy escalation.

Safety of Anti-TNF-Alpha Therapy During Pregnancy on Long-term Outcome of Exposed Children: A Controlled, Multicenter Observation.

BACKGROUND: Evidence of the impact of in utero exposure to anti-tumor necrosis factor (TNF)-alpha on long-term childhood development is limited. The aim was to assess the impact of in utero exposure to anti-TNF-alpha due to mothers' inflammatory bowel disease (IBD) on long-term postnatal development of exposed children. METHODS: We included consecutive children (≥12 months of age) born to mothers with IBD (2007-2016) treated with anti-TNF-alpha during pregnancy in 3 centers in the Czech Republic. A control group was comprised of unexposed children of non-IBD mothers undergoing mandatory check-ups at general pediatricians' offices. Data on perinatal period, psychomotor development, vaccination, infections, antibiotics, and allergy were collected by treating pediatricians using a predefined questionnaire. RESULTS: Seventy-two exposed and 69 unexposed children were included (median age, 35 and 50 months, respectively). Exposed children had growth and psychomotor development similar to controls. There was no significant difference in infectious complications within the first year of life (23.9% vs 17.4%; P = 0.36) or during the whole follow-up between exposed infants and controls (P = 0.32). Concomitant immunosuppressants during pregnancy and anti-TNF-alpha levels in cord blood were not associated with elevated infection rate within the first year of life (P > 0.05). Over 95% of exposed children had adequate serologic response to vaccination, except for haemophilus and mumps vaccines. Clinically manifested allergy was similar between the groups (P = 0.98). CONCLUSIONS: Anti-TNF-alpha exposure in utero does not seem to have a negative impact on postnatal development of children with regard to infectious complications, allergy, growth, or psychomotor development when compared with unexposed children of non-IBD women.

Infliximab biosimilar CT-P13 therapy is effective in maintaining endoscopic remission in ulcerative colitis - results from multicenter observational cohort.

BACKGROUND: CT-P13, the first biosimilar monoclonal antibody to infliximab (IFX), has previously been confirmed to be efficacious in inducing mucosal healing in ulcerative colitis (UC) patients. The aim of this study was to evaluate the efficacy of CT-P13 therapy in maintaining mucosal healing in UC. METHODS: CT-P13 trough levels, antibody positivity, serum inflammatory markers as CRP level, fecal calprotectin at weeks 14 and 54, concomitant steroid and azathioprine therapy at the time of induction therapy and at weeks 14 and 54, previous use of anti TNF drug and the need of dose intensification as possible predictive factors for mucosal healing at week 54 were evaluated in this prospective study. RESULTS: 61 patients had already completed the 54-week treatment period. Mucosal healing was shown in 65.5 % and 62.1 %, complete mucosal healing was present in 31% and 38 % at week 14 and 54, respectively. The median values of CRP, leukocytes, thrombocytes, and albumin showed significant difference between baseline and week 54. Serum antibody positivity was proved in 6.5 % and 19.7 % of cases at week 14 and 54, respectively. CONCLUSION: Our study confirmed the long-term efficacy of CT-P13 therapy on mucosal healing in UC.

Evaluation of Infliximab Therapy in Children with Crohn's Disease Using Trough Levels Predictors.

BACKGROUND: In adults, infliximab (IFX) levels correlate with disease activity, and antibodies to IFX (ATIs) predict treatment failure. We aimed to determine the association of IFX levels and ATIs with disease activity in a paediatric population. We prospectively collected blood, stool, and clinical data from 65 patients (age 10.5-15.1 years) with Crohn's disease (CD) before IFX administration, and measured IFX trough levels, ATIs, and faecal calprotectin levels (CPT). Samples were collected during maintenance therapy. We used multivariate analysis to identify the predictors of IFX levels. SUMMARY: Lower levels of IFX were associated with ATIs positivity (OR 0.027, 95% CI 0.009-0.077). Higher C-reactive protein (CRP) level, erythrocyte sedimentation rate, and CPT levels were found in patients with lower IFX levels. The optimal combination of sensitivity (0.5) and specificity (0.74) for disease activity was calculated for IFX levels ≥1.1 µg/mL using CRP level <5 mg/L as a marker of laboratory remission. In a model that used CPT ≤100 µg/g as the definition of remission, the optimal IFX trough level was 3.5 µg/mL. No independent association between remission and ATIs was found in our study population. However, we found an independentz association between IFX levels and serum albumin levels (OR 1.364, 95% CI 1.169-1.593), p < 0.001. Key Messages: The paediatric population was similar to adult populations in terms of the association between IFX and ATIs as well as between IFX and disease activity.

Fecal zonulin is elevated in Crohn's disease and in cigarette smokers.

OBJECTIVES: Human zonulin is a protein that increases permeability in the epithelial layer of the small intestine by reversibly modulating the intercellular tight junctions. There is not sufficient information available about zonulin's participation in inflammatory bowel diseases (IBD). The aim of this study was therefore to investigate fecal and serum zonulin in IBD patients and its relation to the disease localization, behavior and smoking status. DESIGN AND METHODS: Forty IBD patients and forty healthy persons were examined for fecal and serum zonulin concentrations by competitive ELISA (DRG International Inc). Values were correlated to IBD type, localization and behavior, and smoking. RESULTS: Serum and fecal zonulin were significantly higher in patients with Crohn's disease compared to ulcerative colitis (p = 0.038 for fecal zonulin, and p = 0.041 for serum zonulin concentrations). No association of serum or fecal zonulin was found with respect to IBD localization and behavior. The only difference was found with respect to smoking. Both the IBD cohort and healthy smokers showed significantly higher fecal zonulin levels (median 203 ng/mL) compared to non-smokers (median 35.8 ng/mL), p < 0.001. CONCLUSIONS: Fecal and serum zonulin levels are elevated in patients with active Crohn's disease but not with ulcerative colitis. High fecal zonulin levels in smokers irrespective of IBD point to the significant and undesirable up-regulation of gut permeability in cigarette smokers.

Frequency and characteristics of infusion reactions during biosimilar infliximab treatment in inflammatory bowel diseases: results from Central European nationwide cohort.

BACKGROUND: Safety data of the 'real life' use of an infliximab biosimilar, CT-P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess the frequency and characteristics of infusion reactions during CT-P13 therapy in 13 Hungarian and 1 Czech IBD centres. METHODS: Clinical and safety data was registered at fixed appointments. Trough levels and anti-drug antibody (ADA) concentration were measured by ELISA. Association between demographic, clinical, laboratory parameters and infusion reaction rates were evaluated statistically. RESULTS: Three hundred and eighty-four IBD patients were included. Twenty-eight Hungarian IBD patients (9.6%) developed infusion reaction during the treatment, 64.3% of them was previously exposed to anti TNF therapy. No infusion reaction occurred in the Czech population. CT-P13 therapy had to be stopped in 17 patients who developed infusion reaction and was switched to adalimumab in 12 patients. However in 39.3% of patients developing infusion reaction CT-P13 therapy was continued with the use of premedication. Cumulative ADA positivity rates were 8.7%, 19.3%, and 28.0% at weeks 0, 14, and 30. Previous anti-TNF-alpha exposure (30% vs. 3.1%, p < 0.001, OR 6.3 (2.7-14.6)) and ADA positivity (32.6% vs. 4.1%, p < 0.001, OR 19(5-73)) during the induction therapy were predictive factors for infusion reactions. CONCLUSIONS: Patients with previous exposure to anti-TNF-alpha and ADA positivity during the induction therapy were more likely to develop infusion reactions.

Prolonged progesterone administration is associated with less frequent cervicovaginal colonization by Ureaplasma urealyticum during pregnancy - Results of a pilot study.

BACKGROUND: Preterm birth is a leading cause of perinatal mortality and morbidity. Heavy cervicovaginal Ureaplasma colonization is thought to play a role in the pathogenesis of preterm birth. The administration of vaginal progesterone has been shown to reduce the incidence of preterm birth in women with short cervical length. Steroid hormones seem to modulate the presence of microorganisms in the vagina. The aim of this study was to assess whether the treatment with vaginal progesterone could reduce the incidence of preterm birth and cervicovaginal colonization by Ureaplasma urealyticum in a cohort of pregnant women with threatened preterm labor. METHODS: A cohort of 63 females who presented with regular contractions and/or short cervical length between 24-32 weeks of gestation were recruited into a prospective study. 70% of patients had been treated with vaginal progesterone prior to recruitment and these patients continued with the treatment until birth. All patients were tested for the presence of cervicovaginal Ureaplasma urealyticum colonization at admission. The primary endpoint was preterm birth before 37 weeks. RESULTS: The incidence of preterm delivery was significantly increased in patients who tested positive for Ureaplasma urealyticum. Prolonged vaginal progesterone administration was associated with less frequent cervicovaginal colonization by U. urealyticum. Cervicovaginal colonization by U. urealyticum and absence of progesterone treatment were identified as two independent risk factors for preterm delivery. CONCLUSIONS: Our results demonstrate the beneficial effects of progesterone administration in reducing the incidence of cervicovaginal colonization by Ureaplasma urealyticum.

Discontinuation of anti-tumor necrosis factor therapy in inflammatory bowel disease patients: a prospective observation.

BACKGROUND: Discontinuation of anti-TNF therapy in patients with inflammatory bowel diseases (IBD) in remission remains a controversial issue. The aims of our study were to assess the proportion of patients who relapse after cessation of biological treatment, and to identify potential risk factors of disease relapse. METHODS: Consecutive IBD patients who discontinued anti-TNF therapy in steroid-free clinical and endoscopic remission were prospectively followed. Multiple logistic regression and Cox proportional-hazards models were used to assess the predictors of disease relapse. RESULTS: Seventy-eight IBD patients (Crohn's disease, CD 61; ulcerative colitis, UC 17) were included and followed for a median of 30 months (range 7-47). A total of 32 (53%) CD patients and nine (53%) UC patients relapsed by the end of the follow-up with a median time to relapse of 8 months (range 1-25) in CD patients and 14 months (range 4-37) in UC patients, respectively. The cumulative probabilities of maintaining remission at 6, 12, and 24 months were 82%, 59%, and 51% in CD patients, and 77%, 77%, and 64% in UC patients, respectively. Survival of CD patients who were in deep remission (clinical and endoscopic healing; faecal calprotectin <150 mg/kg; CRP ≤5 mg/l) was not better compared with those who did not fulfill these criteria. In multivariate models, only colonic CD protected patients from disease relapse. CONCLUSIONS: Approximately half of the IBD patients relapsed within 2 years after anti-TNF discontinuation. In CD patients, no difference between those who were or were not in deep remission was found. Colonic localization protected patients from relapse.

Diagnostic and prognostic value of presepsin in preterm deliveries.

PROBLEM: To evaluate the association between serum presepsin (soluble CD14 antigen subtype, sCD14-ST) levels soon after the appearance of signs of preterm delivery and preterm delivery within 48 h, before the 34th and 37th gestational weeks and the possible additional value of concurrently evaluated ultrasound vaginal cervicometry with serum presepsin measurement. METHODOLOGY: A total of 60 females were included. Serum presepsin was measured by a chemiluminescent immunoassay. Sonographic evaluation of cervical length in all females was conducted by transvaginal ultrasound. RESULTS: Patients who delivered within 48 h after analysis showed significantly higher presepsin concentrations compared to females with later deliveries. Higher presepsin was proven also for deliveries before/after weeks 34 and 37. A combined finding of cervical length shortening below 18 mm and presepsin level increasing above 623.5 pg/mL could point to the significantly high risk of preterm delivery. CONCLUSION: Elevated maternal serum concentration of sCD14-ST could be an independent and relevant risk factor for preterm delivery.

Low levels of circulating T-regulatory lymphocytes and short cervical length are associated with preterm labor.

Recent discoveries suggest that T-regulatory lymphocytes (Treg) might play an important role in the pathophysiology of preterm labor. The aim of this study was to assess the relationship among the levels of maternal circulating Treg cells, uterine cervical length, and the risk of preterm labor. Sixty women with regular contractions and/or cervical incompetence at 24-32 weeks' gestation were recruited into a prospective study. Each patient underwent transvaginal ultrasound examination of the cervical length, and regulatory T cells were quantified in peripheral blood samples by flow cytometry. Patients with cervical incompetence were prescribed vaginal progesterone until birth. Measurements of Treg levels and cervical length correlated with the timing of labor. The risk of preterm labor happening within 48 h of testing was demonstrated to be almost 35 times higher (OR=35.21, CI 13.3; 214, p<0.001) in the group with simultaneously low Treg values (<0.031 × 10(9)/L) and a shortened uterine cervix (<17.5mm), compared with the situation where both of these values were normal. Similar results were found in predicting preterm delivery before 34 weeks, or between 34 and 37 weeks. A statistically nonsignificant trend toward increased cervical length and increased Treg count was noted in the women on progesterone treatment. We show for the first time that the combined assessment of Treg cell count and cervical length is a much better predictor of preterm delivery than either parameter used on its own. This combined approach may offer clinical application in patients who present with risk factors for preterm labor.

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 α (TNF-α) 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-α 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 children's 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-α 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.

Pitfalls in the laboratory assessment of serum prealbumin levels in hemato-oncological patients.

BACKGROUND: To highlight specific aspects of serum prealbumin measurements in hemato-oncological patients. METHODS: Retrospective analysis of 4911 serum prealbumin measurements with special attention to values from hemato-oncological Intensive Care Units (ICU) patients. RESULTS: Prealbumin serum levels in hemato-oncological ICU patients (n = 530) were significantly higher when compared to other ICU cohorts (p < 0.0001). Their prealbuminemia did not correlate with serum albumin (p = 0.104) and was not affected by serum cholesterol or triglycerides (p = 0.076 and p = 0.430, respectively). Surprisingly, serum prealbumin has shown a positive correlation with cyclosporine in whole blood levels (r = 0.269, p = 0.010). CONCLUSIONS: A supposed explanation for our findings probably lies in a combination of several factors, including interference with the analysis itself and contamination or possible interference with the medication, e.g., cyclosporine. The prealbumin values do not reflect the actual nutritional state and cannot be regarded as a useful marker of malnutrition in these patients.

Pregnancy and newborn outcome of mothers with inflammatory bowel diseases exposed to anti-TNF-α therapy during pregnancy: three-center study.

OBJECTIVE: Substantial number of women with inflammatory bowel disease (IBD) conceives while on anti-TNF-α therapy. The aim was to assess the safety and efficacy of anti-TNF-α treatment during pregnancy and to analyze relationship of neonatal and maternal anti-TNF-α levels at delivery with gestational age at the last exposure. MATERIAL AND METHODS: Women with IBD exposed to anti-TNF-α therapy during pregnancy were included. Data on anti-TNF-α treatment, disease activity, concomitant medication, pregnancy and newborn outcome were recorded. Anti-TNF-α levels from cord blood were assessed by ELISA. RESULTS: Forty-one pregnancies (27 Crohn's disease; 14 ulcerative colitis) were exposed to infliximab (IFX; 32) and adalimumab (ADA; 9). Ten (24%) women had active disease at conception and 31 (76%) were in remission with 3 patients experiencing relapse during pregnancy. Anti-TNF-α therapy started prior to and after conception in 32 and 9 women, respectively. There were 34 (83%) live births (median birth weight 3145 g) of which 28 were at-term and 6 preterm deliveries. Five (12%) pregnancies ended in spontaneous and two in therapeutic abortion. No congenital malformations except for one case of hip dysplasia were observed. Similarly, no serious perinatal complication occurred. IFX cord levels measured in 11 children positively correlated with gestational week at the last drug administration and maternal levels at delivery, while no such correlation was found in case of ADA. CONCLUSIONS: The results confirm that anti-TNFs are effective and safe during pregnancy. A positive correlation between IFX cord levels and gestational week of last exposure as well as maternal serum levels was observed.

Substantially elevated C-reactive protein (CRP), together with low levels of procalcitonin (PCT), contributes to diagnosis of fungal infection in immunocompromised patients.

PURPOSE: Serum procalcitonin (PCT) has become a routinely utilized parameter with a high prediction value of the severity of bacterial infectious complications and their immediate outcomes. Whereas the utility of PCT in differentiating between bacterial and viral infection is generally accepted, its significance in fungal infections has yet to be determined. The aim of the study was to determine the role of PCT testing in patients at high risk for invasive fungal infections. METHODS: Immunocompromised hematological patients undergoing cyclic chemotherapy treatment or allogeneic hemopoietic stem cell transplantation with infectious complications in which the infectious agents were identified during the disease course were evaluated. In patients with bacterial infection, positive hemocultures were documented, and in patients with fungal infection, the presence of either proven or probable disease was confirmed according to Ascioglu criteria. C-reactive protein (CRP) and PCT were prospectively assessed from the day following fever onset, for four consecutive days. RESULTS: Overall, 34 patients were evaluated, 21 with bacterial and 13 with fungal infections. Significant elevations of CRP concentrations (i.e., above the upper normal limit) were observed in all patients, with a tendency toward higher levels in bacterial (both gram-positive [Gr+] and Gr-negative [Gr-]) than in fungal infections. PCT levels were significantly elevated in patients with bacterial infections (e.g., predominantly in Gr- compared to Gr+), whereas in patients with fungal infections, we identified minimal or no PCT elevations, p < 0.01. For the fungal infections, according to constructed receiver operating characteristic curves, a combination of PCT <0.5 µg/L and CRP 100-300 mg/L offers the best specificity, sensitivity and positive and negative predictive values (81, 85, 73, and 89 %, respectively). CONCLUSION: Altogether, our data suggest that the finding of substantially elevated CRP combined with low PCT in immunocompromised patients may indicate systemic fungal infection. The use of this combination might simplify the diagnostic process, which otherwise can often be lengthy and arduous.

Infliximab trough levels may predict sustained response to infliximab in patients with Crohn's disease.

BACKGROUND AND AIMS: Over 10% of Crohn's disease (CD) patients annually lose response to infliximab. Infliximab trough levels (TL), concomitant immunosuppressants and endoscopic healing were proposed as predictors of favourable infliximab outcome. We assessed infliximab TL measured after induction therapy as predictors of sustained clinical response. Furthermore, we tried to identify other predictors of long-term benefit of infliximab therapy. METHODS: We included CD patients treated with infliximab between October 2007 and March 2010 who responded to 3-dose induction followed by maintenance therapy and in whom blood samples taken at treatment week 14 or 22 were available in blood bank. Sustained response to infliximab was defined as absence of treatment failure due to loss of response or drug intolerance. RESULTS: Eighty four patients were included. Sustained response to infliximab was observed in 47 (56%) patients during a median follow-up of 25 months (14-37). Infliximab TL>3µg/ml were associated with a decreased risk of treatment failure (HR 0.34; 95% CI: 0.16-0.75), whereas the presence of antibodies against infliximab and need for corticosteroids increased this risk (HR 4.34; 95% CI: 1.51-12.5 and HR 2.49, 95% CI: 1.08-5.73, respectively). No impact of concomitant thiopurines was observed, although patients receiving thiopurines had higher infliximab TL than those without immunomodulators (5.51 vs. 0.71µg/ml; p=0.01). CONCLUSION: During a median follow up of 2 years sustained response to infliximab was observed in slightly more than half of CD patients. Infliximab TL>3µg/ml at the start of maintenance regime were predicative of sustained response to infliximab.

Intracellular cytokine production in peripheral blood lymphocytes: a comparison of values in infertile and fertile women.

PROBLEM: To analyze the relation of the fertility and pregnancy of women of childbearing age to the intracellular (IC) production of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukins 2 and 4 (IL-2 and IL-4). METHOD OF STUDY: Intracellular cytokine production in peripheral blood CD3(+) CD4(+) lymphocytes was analyzed by flow cytometry in 185 women being treated for infertility and 50 fertile women of childbearing age. RESULTS: Infertile women have a significantly higher IC production of TNF-α, IFN-γ, IL-2, and IL-4 and higher ratios of TNF-α/IL-2, TNF-α/IL-4, and TNF-α/IFN-γ compared to the fertile women. CONCLUSION: Cytokines produced by Th lymphocytes are important in orchestrating the immune response during conception, and Th-cell dysregulation could be a reason for infertility.

Anti-inflammatory effect of biological treatment in patients with inflammatory bowel diseases: calprotectin and IL-6 changes do not correspond to sRAGE changes.

AIM: The main objective was to examine the relationship between the soluble receptor for advanced glycation end products (sRAGE) and calprotectin concentrations in faeces and serum of patients with inflammatory bowel diseases (IBD) during biological treatment with infliximab. MATERIALS AND METHODS: A total of 29 IBD patients treated with infliximab were evaluated. Calprotectin and sRAGE in serum and faeces and serum IL-6 and CRP were measured during the induction regimen of infliximab treatment at weeks (W) 0, 2 and 10. RESULTS: At W0, a significant increase in faecal calprotectin was found in IBD compared to healthy persons (690 +/- 696 microg/g and 23 +/- 7 microg/g, respectively, p < 0.001). No clear difference was found in serum sRAGE levels in IBD cohort compared to healthy controls (772 +/- 274 pg/mL and 720 +/- 107 pg/mL, respectively, p = 0.159); however, a significant negative correlation was found between faecal calprotectin levels and serum concentrations of sRAGE in the active IBD cohort (r = -0.518, p = 0.004). In the stool eluates, sRAGE levels were non-measurable. In the group of responders-to-treatment, the initial surge in both faecal and serum calprotectin levels as well as CRP and IL-6 was followed by a significant decrease on W10. Surprisingly, no significant changeovers were seen in serum sRAGE concentrations in responders neither in W2 nor in W10. CONCLUSIONS: Unlike other examined local and systemic inflammatory markers, serum sRAGE did not change during the infliximab treatment, despite the initial correlation with the degree of mucosal inflammation.

Changes of immunological profiles in patients with chronic myeloid leukemia in the course of treatment.

In the previous paper of ours we compared, prior to start any treatment, a number of immunological parameters in 24 chronic myeloid leukemia patients with the same number of healthy subjects matched by age and sex. We found significant differences in the levels of immunoglobulins, the C4 component of complement, the C-reactive protein, interleukin 6, the composition of lymphocyte population and the production of some cytokines by stimulated CD3+ cells. Eleven of these patients were followed longitudinally. After treatment with hydroxyurea, interferon alpha, imatinib mesylate and dasatinib, or various combinations thereof, hematological remission was achieved in all patients and complete cytogenetic remission in nine of them. There was a nearly general tendency towards normalization of the abnormalities observed in the patients at their enrollment.

Anticarbohydrate antibodies as markers of inflammatory bowel disease in a Central European cohort.

BACKGROUND: The study discusses the role of antichitobioside carbohydrate antibody (ACCA), antilaminaribioside carbohydrate antibodies (ALCA), and antimannobioside carbohydrate antibodies (AMCA) in Central European patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Twohundred and seventy-two serum samples were used - 116 Crohn's disease (CD), 84 ulcerative colitis, and 72 healthy control samples. All samples were evaluated using enzyme-linked immunosorbent assay for the following four anticarbohydrate assays: ACCA, ALCA, AMCA, and anti-Saccharomyces cerevisiae antibodies (gASCA). RESULTS: gASCA antibodies showed the highest sensitivity (67%) for a CD diagnosis, followed by AMCA (31%), ACCA (27%), and ALCA (25%). Positivity of at least one of the four assays increased the overall sensitivity of antibody testing in CD up to 85.5%. Mean serum gASCA levels were significantly higher in CD patients who were younger at diagnosis and had a longer disease duration before blood sampling (P<0.001). In nonstricturing, nonpenetrating CD, serum gASCA levels were lower than in patients with stricturing and/or penetrating behavior (P<0.05). The strongest association of gASCA was found with ileocolonic CD and with upper gastrointestinal disease (P<0.001). No association between anticarbohydrate (AMCA, ACCA, and ALCA) antibodies and CD location, behavior, age at onset, and disease duration was found; however, that sample size of some of our subgroups was probably too small to make firm conclusions on associations with all CD phenotypes. None of the assessed anticarbohydrate assays was predictive of colonic CD in patients in whom the distinction between CD and ulcerative colitis is not obvious using routine diagnostic methods. There was no relationship between the presence or concentration of anticarbohydrate antibodies and the inflammation measured by C-reactive protein levels. CONCLUSION: The use of a panel of anticarbohydrate antibodies may provide additional help in distinguishing IBD from non-IBD disease patterns. The addition of AMCA, ALCA, and ACCA assays as IBD serology markers improves the overall sensitivity of immunological examinations in IBD; however, anticarbohydrate assays are not helpful for predicting CD behavior.

Detection of galectin-3 in patients with inflammatory bowel diseases: new serum marker of active forms of IBD?

OBJECTIVE: It is an open question whether multifunctional galectin-3 can be a serum marker in inflammatory bowel disease. METHODS: Western blots and commercial ELISA detected and quantitated the lectin immunocytochemistry using double labeling localized it in tissue sections. RESULTS: Serum concentrations were significantly increased in specimen of patients with active and remission-stage ulcerative colitis and Crohn's disease, associated with emerging positivity of CD14(+) cells. CONCLUSION: Enhanced concentration of galectin-3 in serum reflects presence of disease and points to its involvement in the pathogenesis.