Transcriptional response of a target plant to benzoxazinoid and diterpene allelochemicals highlights commonalities in detoxification.

BACKGROUND: Plants growing in proximity to other plants are exposed to a variety of metabolites that these neighbors release into the environment. Some species produce allelochemicals to inhibit growth of neighboring plants, which in turn have evolved ways to detoxify these compounds. RESULTS: In order to understand how the allelochemical-receiving target plants respond to chemically diverse compounds, we performed whole-genome transcriptome analysis of Arabidopsis thaliana exposed to either the benzoxazinoid derivative 2-amino- 3H-phenoxazin-3-one (APO) or momilactone B. These two allelochemicals belong to two very different compound classes, benzoxazinoids and diterpenes, respectively, produced by different Poaceae crop species. CONCLUSIONS: Despite their distinct chemical nature, we observed similar molecular responses of A. thaliana to these allelochemicals. In particular, many of the same or closely related genes belonging to the three-phase detoxification pathway were upregulated in both treatments. Further, we observed an overlap between genes upregulated by allelochemicals and those involved in herbicide detoxification. Our findings highlight the overlap in the transcriptional response of a target plant to natural and synthetic phytotoxic compounds and illustrate how herbicide resistance could arise via pathways involved in plant-plant interaction.

Subunit-selective proteasome activity profiling uncovers uncoupled proteasome subunit activities during bacterial infections.

The proteasome is a nuclear-cytoplasmic proteolytic complex involved in nearly all regulatory pathways in plant cells. The three different catalytic activities of the proteasome can have different functions, but tools to monitor and control these subunits selectively are not yet available in plant science. Here, we introduce subunit-selective inhibitors and dual-color fluorescent activity-based probes for studying two of the three active catalytic subunits of the plant proteasome. We validate these tools in two model plants and use this to study the proteasome during plant-microbe interactions. Our data reveal that Nicotiana benthamiana incorporates two different paralogs of each catalytic subunit into active proteasomes. Interestingly, both ß1 and ß5 activities are significantly increased upon infection with pathogenic Pseudomonas syringae pv. tomato DC3000 lacking hopQ1-1 [PtoDC3000(ΔhQ)] whilst the activity profile of the ß1 subunit changes. Infection with wild-type PtoDC3000 causes proteasome activities that range from strongly induced ß1 and ß5 activities to strongly suppressed ß5 activities, revealing that ß1 and ß5 activities can be uncoupled during bacterial infection. These selective probes and inhibitors are now available to the plant science community, and can be widely and easily applied to study the activity and role of the different catalytic subunits of the proteasome in different plant species.

Screen of Non-annotated Small Secreted Proteins of Pseudomonas syringae Reveals a Virulence Factor That Inhibits Tomato Immune Proteases.

Pseudomonas syringae pv. tomato DC3000 (PtoDC3000) is an extracellular model plant pathogen, yet its potential to produce secreted effectors that manipulate the apoplast has been under investigated. Here we identified 131 candidate small, secreted, non-annotated proteins from the PtoDC3000 genome, most of which are common to Pseudomonas species and potentially expressed during apoplastic colonization. We produced 43 of these proteins through a custom-made gateway-compatible expression system for extracellular bacterial proteins, and screened them for their ability to inhibit the secreted immune protease C14 of tomato using competitive activity-based protein profiling. This screen revealed C14-inhibiting protein-1 (Cip1), which contains motifs of the chagasin-like protease inhibitors. Cip1 mutants are less virulent on tomato, demonstrating the importance of this effector in apoplastic immunity. Cip1 also inhibits immune protease Pip1, which is known to suppress PtoDC3000 infection, but has a lower affinity for its close homolog Rcr3, explaining why this protein is not recognized in tomato plants carrying the Cf-2 resistance gene, which uses Rcr3 as a co-receptor to detect pathogen-derived protease inhibitors. Thus, this approach uncovered a protease inhibitor of P. syringae, indicating that also P. syringae secretes effectors that selectively target apoplastic host proteases of tomato, similar to tomato pathogenic fungi, oomycetes and nematodes.

[Surgical ventricular reconstruction for ischemic left ventricular aneurysm. Early and medium-term outcomes for two surgical techniques]. / Az ischaemiás eredetu balkamra-aneurysma sebészi rekonstrukciója. Két sebészi technika korai és középtávú eredményei.

INTRODUCTION: Left ventricular aneurysm is a severe complication of acute myocardial infarction, which contributes significantly to mortality and morbidity associated with this pathology. Despite the progress of correction techniques, there are still controversies about the optimal approach addressing this pathology. AIM: The aim of this study was to analyse short and medium term outcomes of left ventricular reconstruction for ischemic left ventricular aneurysm using two surgical techniques (endoventricular patch plasty and liniar suture) in order to determine if one of these techniques has supperior results. METHOD: 117 patients were included in the study, 48 patients (41%) underwent left ventricular reconstruction with endoventricular patch (Group 1), 69 patients (59%; Group 2) had linear reconstruction. 113 patients (96.5%) required associated procedures: 108 surgical myocardial revascularization, 18 mitral valvuloplasty and 8 ventricular septal defect closure. Short and medium term morbidity, mortality, alteration of ejection fraction and NYHA class were analysed. RESULTS: Perioperative mortality was 11.11%, 4.2% in the endoventricular patch group, and 15.9% in the linear suture group (p = 0.03). The overall 5-year survival was 78.5% (88.7% in Group 1 and 71.2% in Group 2). The left ventricular ejection fraction and NYHA functional class improved in both groups, with greater improvement in the endoventricular patch group. CONCLUSIONS: Surgical ventricular reconstruction is a procedure performed for the correction of ischemic left ventricular aneurysm with good early and medium-term results, but with better results with the endoventricular patch technique regarding early and medium-term mortality, ejection fraction and NYHA functional class improvement. Orv Hetil. 2018; 159(51): 2167-2174.

Antimicrobial and Virulence-Modulating Effects of Clove Essential Oil on the Foodborne Pathogen Campylobacter jejuni.

Our study investigated the antimicrobial action of clove (Syzygium aromaticum) essential oil (EO) on the zoonotic pathogen Campylobacter jejuni After confirming the clove essential oil's general antibacterial effect, we analyzed the reference strain Campylobacter jejuni NCTC 11168. Phenotypic, proteomic, and transcriptomic methods were used to reveal changes in cell morphology and functions when exposed to sublethal concentrations of clove EO. The normally curved cells showed markedly straightened and shrunken morphology on the scanning electron micrographs as a result of stress. Although, oxidative stress, as a generally accepted response to essential oils, was also present, the dominance of a general stress response was demonstrated by reverse transcription-PCR (RT-PCR). The results of RT-PCR and two-dimensional (2D) PAGE revealed that clove oil perturbs the expression of virulence-associated genes taking part in the synthesis of flagella, PEB1, PEB4, lipopolysaccharide (LPS), and serine protease. Loss of motility was also detected by a phenotypic test. Bioautographic analysis revealed that besides its major component, eugenol, at least four other spots of clove EO possessed bactericidal activity against C. jejuni Our findings show that clove EO has a marked antibacterial and potential virulence-modulating effect on C. jejuni IMPORTANCE: This study demonstrates that the components of clove essential oil influence not only the expression of general stress genes but also the expression of virulence-associated genes. Based on this finding, alternative strategies can be worked on to control this important foodborne pathogen.

Twelve ways to confirm targets of activity-based probes in plants.

Activity-based probes are powerful tools to interrogate the functional proteome. Their covalent and often irreversible labeling of proteins facilitates the purification, identification and quantification of labeled proteins. However, the detection of labeled proteins often requires a confirmation, especially when unexpected proteins are identified, or to unravel fluorescent activity profiles. Here, we review twelve approaches towards target confirmation, grouped in approaches by direct target detection, target expression or target depletion. We discuss their proper use and limitations and illustrate these approaches with examples from plant science.

Baseline Characteristics and Disease Phenotype in Inflammatory Bowel Disease.

OBJECTIVES: Predicting short-term relapses and long-term prognosis is of utmost importance in paediatric inflammatory bowel disease (IBD). Our aim was to investigate the short-term disease outcome and medication during the first year in a paediatric incident cohort from Hungary. In addition, association laboratory markers and disease activity indices with short-term disease outcome and medication were analysed. METHODS: From January 1, 2008 to December 31, 2010, demographic data and clinical characteristics of newly diagnosed paediatric patients with IBD < 18 years of age were prospectively recorded. RESULTS: A total of 420 patients were identified (Crohn disease [CD] 266 and ulcerative colitis [UC] 124). Initially, 48% (124/256) of the patients with CD had moderate-to-severe disease (Pediatric Crohn's Disease Activity Index [PCDAI] > 31), and this rate decreased to 2.1% at 1-year follow-up. Proportion of patients with UC with moderate-to-severe disease (Pediatric Ulcerative Colitis Activity Index > 35) at diagnosis declined from 57.5% (69/120) to 6.8% at 1-year follow-up. Terminal ileal involvement correlated with higher initial C-reactive protein (CRP) (P = 0.021) and initial PCDAI (P = 0.026). In UC, elevated CRP (P = 0.002) was associated with disease extension. CRP and PCDAI at diagnosis were associated with the need for immunomodulators at 1 year in children with CD. Initial CRP was also associated with the need for immunomodulators in patients with UC at 1-year follow-up. CONCLUSIONS: At diagnosis, half of the patients with IBD had moderate-to-severe disease, and this rate decreased to <10% after 1 year. Initial CRP and PCDAI were related to the need for aggressive therapy in CD.

Salicylic acid induced cysteine protease activity during programmed cell death in tomato plants.

The hypersensitive response (HR), a type of programmed cell death (PCD) during biotic stress is mediated by salicylic acid (SA). The aim of this work was to reveal the role of proteolysis and cysteine proteases in the execution of PCD in response of SA. Tomato plants were treated with sublethal (0.1 mM) and lethal (1 mM) SA concentrations through the root system. Treatment with 1 mM SA increased the electrolyte leakage and proteolytic activity and reduced the total protein content of roots after 6 h, while the proteolytic activity did not change in the leaves and in plants exposed to 0.1 mM SA. The expression of the papain-type cysteine protease SlCYP1, the vacuolar processing enzyme SlVPE1 and the tomato metacaspase SlMCA1 was induced within the first three hours in the leaves and after 0.5 h in the roots in the presence of 1 mM SA but the transcript levels did not increase significantly at sublethal SA. The Bax inhibitor-1 (SlBI-1), an antiapoptotic gene was over-expressed in the roots after SA treatments and it proved to be transient in the presence of sublethal SA. Protease inhibitors, SlPI2 and SlLTC were upregulated in the roots by sublethal SA but their expression remained low at 1 mM SA concentration. It is concluded that in contrast to leaves the SA-induced PCD is associated with increased proteolytic activity in the root tissues resulting from a fast up-regulation of specific cysteine proteases and down-regulation of protease inhibitors.

Potential salivary biomarkers and their genetic effects in a pilot study of adolescent boys with externalizing problems.

AIMS: Beside the well-known stress response marker cortisol, salivary alpha-amylase is receiving increasing attention. Numerous studies have investigated the potential biomarker properties of cortisol mirroring abnormal hypothalamic-pituitary-adrenal axis activity in connection to both internalizing and externalizing behavior problems. The other major physiological system involved in stress reactivity, the sympathetic nervous system activity can be also measured by the surrogate marker of salivary alpha-amylase. Most of the studies applied a stressful situation to obtain inter-individual differences in stress-reactivity, although differences in the baseline level of cortisol have been also shown in relation to externalizing problems. To test the relevance of another (easier) biomarker, we selected to study baseline circadian salivary cortisol and alpha-amylase levels among adolescent boys with externalizing problems. METHODS: Saliva samples were collected at 3 time-points (morning, noon, evening) during 3 consecutive days from 37 inpatient boys (mean age 12.4±1.0). Cortisol and alpha-amylase levels were measured by enzyme-linked immunosorbent and kinetic enzyme assays, respectively. Genetic variants in the hypothalamic-pituitary-adrenal axis and the norepinephrine transporter or catecholamine metabolizing enzymes were tested for potential moderating effects at these salivary biomarkers. RESULTS: Saliva cortisol showed the classical diurnal fluctuation in boys with externalizing problems (possibly from a lower morning level), but it was not modified by the presence of either conduct, oppositional defiant or attention-deficit/hyperactivity disorder. The diurnal fluctuation of the salivary alpha-amylase levels was also typical, but the presence of conduct disorder was associated with significantly lower alpha-amylase activity (p=0.024) among boys with externalizing problems. The catechol-O-methyltransferase Val158Met (rs4680) polymorphism had an additional effect on salivary alpha-amylase: boys with homozygote genotypes had lower alpha-amylase activity at all 3 time-points compared to Val/Met heterozygotes (p=0.045). CONCLUSIONS: Our preliminary data suggest that salivary alpha-amylase might be used to further characterize subgroups within externalizing problems, however, this biomarker might be modified by certain genetic polymorphisms.

Opposite extremes in ethylene/nitric oxide ratio induce cell death in suspension culture and root apices of tomato exposed to salt stress.

The plant hormone ethylene or the gaseous signalling molecule nitric oxide (NO) may enhance salt stress tolerance by maintaining ion homeostasis, first of all K+/Na+ ratio of tissues. Ethylene and NO accumulation increased in the root apices and suspension culture cells of tomato at sublethal salt stress caused by 100 mM NaCl, however, the induction phase of programmed cell death (PCD) was different at lethal salt concentration. The production of ethylene by root apices and the accumulation of NO in the cells of suspension culture did not increase during the initiation of PCD after 250 mM NaCl treatment. Moreover, cells in suspension culture accumulated higher amount of reactive oxygen species which, along with NO deficiency contributed to cell death induction. The absence of ethylene in the apical root segments and the absence of NO accumulation in the cell suspension resulted in similar ion disequilibrium, namely K+/Na+ ratio of 1.41 ± 0.1 and 1.68 ± 0.3 in intact plant tissues and suspension culture cells, respectively that was not tolerated by tomato.

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.

Integrative attitudes of Ukrainian war refugees in two neighboring European countries (Poland and Hungary) in connection with posttraumatic stress symptoms and social support.

Since February 24th, 2022, millions of Ukrainians have sought refuge in other, mainly European countries. Hungary, after Poland, is the second largest host of Ukrainian refugees. Only a portion of them are asylum seekers (~11.0% in Poland and ~ 1.1% in Hungary). The aim of the study is to compare the integrative acculturation attitudes between the war refugees residing in the two European countries. The comparison takes into account both the suffering of posttraumatic stress symptoms and social support. It is the first comparative study of this kind pertaining to the Ukrainian refugees in European countries. The data were obtained by a survey method using the modified CAPI (Computer Assisted Personal Interview) technique. The data analyzed were collected between November 21st and December 20th, 2022 from 728 adult Ukrainian individuals who crossed the borders of Poland and Hungary after February 24th, 2022. The research results show that refugees in Poland perceive significantly more social support and show stronger integrative attitudes than refugees in Hungary. The two samples do not differ regarding the presence of posttraumatic stress. The integrative attitudes proved not to be linked to gender and age, but linked to the host country. Besides social support and the host country, posttraumatic stress also proved to be a significant predictor of integrative attitudes.

[Pulmonary histiocytic sarcoma]. / A tüdo histiocytás sarcomája.

Histiocytic sarcoma is an uncommon hematological malignancy. Its occurrence in the lung is very rare. Due to the small number of cases and the clinical and pathological features of the disease, the diagnosis can be challenging. Its optimal treatment is not yet known, in locally confined cases - depending on the location and size - surgical removal is part of complex oncotherapy. We report the case of a 52-year-old man with a tumor of central localization in the left lung. Pulmonectomy was performed. Histology verified histiocytic sarcoma of the lung. An overview of clinical features of the entity is presented in connection with our case report. Orv Heti. 2023; 164(34): 1350-1357.

S- to N-Acyl transfer in S-acylcysteine isopeptides via 9-, 10-, 12-, and 13-membered cyclic transition states.

S-Acyl cysteine peptides containing α-, ß- or γ-amino acid residues undergo long-range S- to N-acyl transfer to give analogs of native tripeptides and tetrapeptides containing additional carbon atoms in the chain. The ease of intramolecular S → N-acyl transfer relative to intermolecular transacylation is favored increasingly for 9 < 12 < 13 ~ 10-membered cyclic transition states; the observed order is explained on conformational and intermolecular interaction considerations.

Impact of positive intraabdominal lavage cytology on the long-term prognosis of colorectal cancer patients.

BACKGROUND: Our aim was to investigate the presence of free cancer cells found in lavage cytology specimens taken from the proximity of tumors during the course of curative open and laparoscopic colorectal resections and then examine and compare the long-term disease outcomes in cases of negative and positive cytology. Based on the results, we were hoping to identify the place of peritumoral lavage cytology among prognostic factors for disease recurrence. METHODS: Between January 1, 2005 and December 31, 2007 intraoperative peritoneal lavage cytology was performed in 145 patients who underwent curative colorectal procedures. In all, 37 of the procedures were laparoscopic resections. RESULTS: Malignant cells were detected in the intraoperative peritoneal lavage cytology samples from 25 patients. Median follow-up was 47 months (3-81 months). Among the 25 patients with positive cytology; locoregional recurrence or distant metastasis was found in 14 during this period (56 %), whereas among the 120 patients with negative cytology the incidence was 28 (23 %). CONCLUSIONS: The impact of tumor stage, lymph node status, and peritoneal lavage cytology on recurrence rates is significant. Tumor, nodal, and lavage cytology status can be organized hierarchically in relation to time of recurrence. Cytology is most important, with positivity rendering long-term prognosis unfavorable. When comparing surgical techniques (open versus laparoscopic), we found no significant difference in recurrence rates. Our study has shown that conventional peritoneal lavage cytology is a prognostic factor in the case of patients undergoing curative colorectal operations.

[Dysgenetic male pseudohermaphroditism]. / Dysgeneticus pseudohermaphroditismus masculinus.

The authors report a case of a dysgenetic male pseudohermaphroditism with a 45,X/46,XY karyotype in a mosaic form, which was diagnosed in an infant. The one-week-old infant was evaluated because of proximal hypospadias and retention of the right testis. The results of hormonal tests were the followings: serum FSH 5.2 mU/ml; LH: 2.0 mU/ml; testosterone: 144.3 ng/dl; androstendione: 0.42 µg/l; 17-hydroxyprogesterone: 1.12 ng/ml. Chromosomal analysis revealed 45,X/46,XY karyotype. Fluorescent in vitro hybridization showed that 51% of the lymphocytes had the Y chromosome and the SRY gene. Analysis of the SRY showed no deletion in the AZF a,b,c regions. Pelvic magnetic resonance imaging indicated the presence of vagina between the bladder and the rectum, and it showed a mass measuring 15×8 mm in the right inguinal canal as well as an oval gonadal mass with a size of 13×7 mm in the left scrotum. During surgical intervention, performed at the age of one, the right gonad was removed and biopsy of the scrotal testis was performed. Histological examination revealed dysgenetic testis in both sides. The authors emphasize the necessity of cytogenetic and endocrinological investigations of newborns with perineoscrotal hypospadia and bilateral or unilateral maldescent testes immediately after birth. Surgical removal of the dysgenetic testicular tissue located in the abdominal cavity and its histological evaluation provides separation of mixed gonadal dysgenesis, dysgenetic male pseudohermaphroditism, bilateral gonadal dysgenesis and ovotestis in the 45,X/46,XY mosaic cases. An accurate evaluation is necessary for a correct sex assignment and for surgical intervention to prevent neoplastic degeneration of the dysgenetic gonad.

Lack of correlation between the 257C-to-T mutation in the gyrA gene and clinical severity of Campylobacter jejuni infection in a region of high incidence of ciprofloxacin resistance.

BACKGROUND: Fluoroquinolone resistance is increasingly detected in Campylobacter jejuni worldwide. Despite the fact that a point mutation in the gyrA gene has been linked with increased fitness in animals, the association of resistant organisms with more severe infections in man remains controversial. METHODS: Erythromycin and quinolone susceptibility of 147 C. jejuni strains isolated from individual patients with diarrhoea in southwest Hungary were investigated and the molecular background of fluoroquinolone resistance was determined. Hospitalization and the presence of macroscopic blood in the stool were correlated with the presence of 257C-to-T mutation of the gyrA gene causing resistance to fluoroquinolones. RESULTS: Isolates showed an extensive genetic heterogeneity by macrorestriction analysis of the chromosome. While all strains retained susceptibility to erythromycin, 68% were non-susceptible to ciprofloxacin. The mutation causing a Thr-86-to-Ile replacement in the gyrA gene was present in 98% of non-susceptible isolates. Infection caused by isolates containing this mutation did not show any significant association with either hospitalization or with the development of bloody diarrhoea. CONCLUSIONS: Our findings indicate that in a region with high-level ciprofloxacin resistance in C. jejuni, non-susceptibility to this antibiotic did not correlate with the severity of infection.

[To grow up with Crohn's disease]. / Felnoni Crohn-betegséggel.

OBJECTIVE: To assess the characteristics and course of childhood-onset Crohn's disease among Hungarian patients. METHODS: Records of 81 patients admitted between 1984 and 2006 and treated at least for one year until the 18th year of age were reviewed. RESULTS: There was a 62% male dominance and a rate of 12.5% of familial cases. The diagnostic lag was 11.36 (1-96) months. The mean age was 13.6 years (4-17), the activity index was 37.88 (5-80) at diagnosis and the initial frequencies were as follows: ileal affection 87%, stricturing and penetrating forms 27%, perianal manifestation 26%, giant cells or granuloma formation 47%, malnutrition 23,5%, growth failure 11%. Steroid therapy and azathioprin treatment were given in 84% and 62% of the patients, respectively. Biologic treatment was not possible during the study period. 31% of the patients underwent surgery (abdominal surgery 20%, perianal surgery 11%). When patients reached the 18th year of age the mean activity index decreased to 6.63 (0-35), the rate of malnutrition to 9.9% and that of growth failure to 2.5%. All these changes were statistically significant. CONCLUSIONS: Characteristics of childhood-onset Crohn's disease in Hungary are similar to those obtained in other European countries. The prolonged diagnostic lag, the high initial activity index, the granuloma formation and the stricturing/penetrating behavior may predict subsequent complications and need for surgery, and, therefore, justify intense initial therapy. The early introduction of immunomodulatory therapy affects favorably the course of illness.

An algorithm using clinical data to predict the optimal individual glucocorticoid dosage to treat multiple sclerosis relapses.

BACKGROUND: Glucocorticoid (GC) pulse therapy is used for multiple sclerosis (MS) relapse treatment; however, GC resistance is a common problem. Considering that GC dosing is individual with several response-influencing factors, establishing a predictive model, which supports clinicians to estimate the maximum GC dose above which no additional therapeutic value can be expected presents a huge clinical need. METHOD: We established two, independent retrospective cohorts of MS patients. The first was an explorative cohort for model generation, while the second was established for its validation. Using the explorative cohort, a multivariate regression analysis with the GC dose used as the dependent variable and serum vitamin D (25D) concentration, sex, age, EDSS, contrast enhancement on cranial magnetic resonance imaging (MRI), immune therapy, and the involvement of the optic nerve as independent variables was established. RESULTS: In the explorative cohort, 113 MS patients were included. 25-hydroxyvitamin D (25D) serum concentration and the presence of optic neuritis were independent predictors of the GC dose needed to treat MS relapses [(25D): -25.95 (95% confidence interval (CI)): -47.40 to -4.49; p = 0.018; optic neuritis: 2040.51 (95% CI: 584.64-3496.36), p = 0.006]. Validation of the multivariate linear regression model was performed within a second cohort. Here, the predicted GC dose did not differ significantly from the dose administered in clinical routine (mean difference: -843.54; 95% CI: -2078.08-391.00; n = 30, p = 0.173). CONCLUSION: Our model could predict the GC dose given in clinical, routine MS relapse care, above which clinicians estimate no further benefit. Further studies should validate and improve our algorithm to help the implementation of predictive models in GC dosing.

Prediction of clinical and mucosal severity of coeliac disease and dermatitis herpetiformis by quantification of IgA/IgG serum antibodies to tissue transglutaminase.

OBJECTIVES: We analysed whether the quantification of autoantibodies against tissue transglutaminase could be used to predict mucosal destruction and disease severity in patients with gluten sensitivity. PATIENTS AND METHODS: One hundred seventy patients with coeliac disease (CD), comprising 52 children with severe malabsorption (group I), 59 children with mild symptoms (group II), 59 adults (group III), 134 patients with dermatitis herpetiformis (DH), and 131 disease controls, were studied. Serial serum samples of patients in groups I and II on a gluten-free diet were also included. Serum levels of antibodies against recombinant tissue transglutaminase were determined with ELISA using standard curves for quantification of antibodies. RESULTS: Immunoglobulin (Ig)A antibodies against tissue transglutaminase (IgA-TGA) were detected in all of the patients with CD and in 95% of the DH patients. The IgA-TGA and IgG-TGA levels were higher in group I (P < 0.001). The IgG-TGA levels and positivity rate in group I (100%) were higher than in group II (81%), group III (73%), and the DH group (67%). Elevated IgA-TGA and IgG-TGA levels in combination predicted a more severe small intestinal atrophy (P < 0.0001) with a specificity of 99% for Marsh IIIb-IIIc (flat) lesions. The kinetics of the IgA-TGA decrease during diet differed between groups I and II. CONCLUSIONS: High levels of IgA-TGA and IgG-TGA antibodies were associated with the grade of mucosal villous atrophy and a more severe clinical presentation. The combined measurement of IgA-TGA and IgG-TGA enables a noninvasive prediction of small intestinal villous atrophy with high accuracy, and may reduce the need for a biopsy in patients with suspected CD.