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Background The HLADQA1*05 variant increases the risk of developing antibodies against infliximab and adalimumab. Whether proactive therapeutic drug monitoring (PTDM) could overcome this immunogenicity remains unknown. The primary aim was to evaluate the influence of the allele HLADQA1*05 on treatment persistence. Methods We performed a single centre retrospective cohort study. IBD patients starting anti-TNF therapy between January, 2017 and March, 2021 were included. HLA DQA1*05 genotype screening was performed during, 2021. PTDM was defined as periodic drug level measurement (≥2 determinations during the first year of treatment and ≥1/annual determination during the following years), regardless of clinical condition, with according dose optimization. Patients not fulfilling these criteria were excluded. Target concentration during induction:, 25–30 mcg/ml (week, 2) and, 20 mcg/ml (week, 6) for Infliximab and >, 10 mcg/ml (week, 2 and, 4) for Adalimumab. During maintenance:, 3–10 mcg/ml for Infliximab and, 8–12 mcg/ml for Adalimumab. Clinical remission was defined as HBI 1 and biochemical remission as a fecal calprotectin Results 126 patients started anti-TNF therapy during the study period. Fourteen were excluded (8 lacked PTDM and, 6 declined the HLA DQA1*05 genotype), thus including, 112 patients with a median follow-up of, 73.9 (IQR:, 35.4–133.1) weeks, 52 (46.4%) HLADQA1*05 positive. Figure, 1 presents baseline characteristics. Combination therapy with thiopurines was more frequent among HLADQA1*05 negative patients (28 (46.7%) vs, 12 (23.1%), p=0.01). During their first year, patients underwent a median of, 3 (IQR, 2–4) drug level measurements. We performed, 497 determinations (4/patient (IQR:3–6);, 149 (30%), drove to dose modifications, 63 (42.3%) among symptomatic patients and, 86 (57.7%) among asymptomatic ones. Primary nonresponses were higher (8.1% vs, 0, p=0.06) among HLADQA1*05 negative patients. The HLADQA1*05 positive presented non-significant higher clinical remission rates at week, 14 (77.9% vs, 73.9%, p=0.69) and, 56 (73.2% vs, 68.4%, p=0.64) (figure 2). Figures, 3 and, 4 presents drug persistence, which was higher among HLADQA1*05 positive patients (HR:, 0.32, 95% CI:, 0.14–0.71, p=0.01). Multivariable Cox regression analysis identified systemic steroids at anti-TNF initiation (Hazard ratio (HR):, 4, 95% CI, 1.7–9.7) as a risk factor and a positive HLA DQA1*05 genotype (HR:0.31 (0.12–0.81)) as a protective factor of treatment cessation. Fig.1 Fig. 2. Fig.3 Fig.4. Conclusion: When PTDM is performed, a positive HLA DQA1*05 genotype does not associate a higher risk of treatment cessation.

Celiac disease (CD) is a chronic immune-mediated enteropathy, resulting from a gluten intolerance in genetically predisposed individuals.a) to describe clinical features, associated disorders and serology of CD in adults; and b) to study the main that serology displays in diagnosis, clinical and histological expression.31 patients diagnosed of CD in adulthood have been reviewed retrospectively, including clinical presentation, associated disorders, biochemical results, serological tests (anti-gliadin and anti-endomysial antibodies) and genetical features (HLA-DQ2). It has been studied the relation between typical presentations and AEm with clinical, serological or histological findings.Almost 50% of patients had atypical clinical manifestations and gastrointestinal symptoms were absent in 33%. Typical manifestations are associated with villous atrophy stage III b-c of Marsh's classification (87 vs. 53%, p = 0,03). 70% of patients shows AEm mostly in women (78 vs. 37%, p = 0.03) and stage III b-c of Marsh (84 vs. 50%, p = 0.05). 68,4% were DQ2 positive.Clinical features of CD varies greatly. AEm and DQ2 are less common than others studies. There may be an association with clinical and serological findings and villous atrophy stage. Genetical features could help AEm in diagnosis.

Introducción: la enfermedad celiaca (EC) es una enteropatía crónica de base inmune debida a una intolerancia al gluten en sujetos genéticamente predispuestos. Objetivos: a) describir clínica, enfermedades asociadas y serología en la EC del adulto; y b) estudiar la utilidad de la serología en el diagnóstico y su relación con la expresión clínica e histológica. Pacientes y métodos: se han estudiado de forma retrospectiva 31 pacientes adultos con diagnóstico de EC seguidos en consulta. Se recogieron datos referidos a los síntomas de presentación, enfermedades asociadas, bioquímica, serología (anticuerpos antigliadina y AEm) y genética (HLA DQ2). Se comprobó si la clínica típica o la positividad de AEm se asociaban a diferencias clínicas, serológicas o grado de atrofia vellositaria. Resultados: prácticamente el 50% de los pacientes tuvo manifestaciones clínicas atípicas y el 33% no tuvo síntomas gastrointestinales. La clínica típica se asoció a atrofia de vellosidades grado III b-c de Marsh (87 vs. 53%, p = 0,03). El 70% de los pacientes tuvo anticuerpos AEm positivos. Entre los pacientes con AEm fueron más frecuentes las mujeres (78 vs. 37%, p = 0,03) y la atrofia de vellosidades grado III b-c de Marsh (84 vs. 50%, p = 0,05). En el estudio genético, el 68,4% (13/19) eran portadores de los dos alelos. Conclusiones: la clínica de la EC del adulto es muy variable. La frecuencia que encontramos de AEm y genética (DQ2) es menor a la publicada. Clínica, grado de atrofia y serología podrían interrelacionarse. La genética puede complementar a los AEm en el diagnóstico.

Mortality due to meningococcal sepsis continues to be extremely high. Patients with a poor prognosis require aggressive therapy and should be identified early.To investigate the clinical and biological factors associated with poor outcome.Seventy-one children aged 2 months to 13 years with meningococcal sepsis were studied. Inclusion criteria were meningococcus isolation in cultures or characteristic clinical features with purpuric exanthema.A correlational descriptive study was performed. In all patients we evaluated the Pediatric Risk of Mortality (PRISM), the Glasgow Scale for Meningococcal Sepsis (GSMS), polymorphonuclear (PMN) count and prolactin (PRL), leptin (LPT) and C-reactive protein (CRP) levels.Fourteen children (19.7 %) died. Death was associated with multiple organ dysfunction syndrome (MODS) (p = 0.0001), high GSMS and PRISM scores (p = 0.0001) and to a lesser extent with shock (p = 0.01). In patients who died, the determinations showing greatest alteration at admission were PRL levels (p = 0.0009) and PMN count (p = 0.0005). CRP levels were not associated with differences in mortality but were high in patients with shock (p = 0.008). Children with high body weight percentiles were at greater risk of death and showed higher levels of PRL, PCT (p = 0.006) and LPT (p = 0.006), without differences in GSMS or PRISM scores. Age did not influence mortality or PRL levels but did influence GMSM and PRISM scores and PMN and CRP levels. These differences disappeared after the age of 2-3 years. In patients with MODS or shock, the only differences found were reduced PMN count (p = 0.0001) and elevated PRL levels (p = 0.0001).In meningococcal sepsis, death is more frequent in children with high body weight percentiles. Moreover, these children present elevated PRL and LPT levels, although whether these variables act independently remains to be elucidated.

To analyze the efficiency of the method of neonatal screening for cystic fibrosis (CF) used in Castille and Leon (Spain), which is carried out with blood from Guthrie spots.A total of 36,086 newborns were studied from January 1999 to June 2001. Immunoreactive trypsinogen (IRT) was quantified in all samples and genetic study covering 87.5 % of mutations in the CFTR gene was carried out when IRT levels were60 ng/mL. The sweat test was performed in all children in whom at least one mutation was detected.IRT values of60 ng/mL were found in 285 children (0.79 %). Of these, eight children (2.8 %) were diagnosed with CF and a further 11 children (3.9 %) with a negative sweat test were found to have one mutation and were thus classified as healthy carriers. To date, no false negatives have been detected.The two-stage screening method fulfills the required criteria. Its sensitivity is 98.5 % and the basic model can be used in other regions although genetic screening should be optimized by pilot programs to identify the local spectrum of CFTR mutations.

The purpose of this study was to assess the frequency of antineutrophil cytoplamic antibodies (ANCA) in Schönlein-Henoch purpura (SHP) and its long-term significance.IgG and IgA classes of ANCA were studied by indirect immunofluorescence (IIF) and IgG-ANCA against myeloperoxidase (MPO) and against proteinase-3 (PR-3) were determined by ELISA in 50 children with SHP. Eight (16%) of the patients had renal involvement during the acute phase, but none had a permanent nephropathy after a 7-17 year follow-up.Positive IgG ANCA were found in 5 (10%) of the cases and only one of these children also had IgA ANCA. The ELISA against MPO and P-3 was negative in all patients. None of the 5 patients with ANCA showed nephropathy during the acute phase nor relapses or permanent nephropathy.A minority of children with SHP are positive for ANCA and, in the absence of nephropathy, this is not associated with a bad long-term prognosis.

IgA and IgG antibodies can be detected in saliva in order to assess the immune status against measles, rubella and mumps.Serum and saliva were simultaneously obtained from 50 adults between 19 and 52 years of age that were non-vaccinated and from 50 children from 15 months to 13 years of age that had been vaccinated against measles, rubella and mumps at 15 months of age. Specific IgG and IgA antibodies were determined by ELISA. Values higher than the 95% confidence interval obtained in 39 non-vaccinated and non-infected infants were considered as positive.In adults 96-100% and in children 90-98% were seropositive for the viral antigens studied. A positive result in saliva was always higher than 50%, with the percentage being higher in children than in adults and mainly for IgA antibodies. According to the present study, the combined determination of IgG and IgA antibodies in saliva would detect 86% of the children seropositive for measles, 87% for rubella and 82% to mumps, with these results being slightly lower in adults. Children without salivary antibodies were frequently younger than 3 years of age and were negative for more than one viral antigen.The study of salivary antibodies is a non-invasive method to assess seropositivity against measles, rubella and mumps, but it is advisable that both IgG and IgA antibodies be determined.

The levels of soluble interleukin-2 receptor (sIL-2R) were measured in 35 serum samples from children with food intolerance; 19 had an IgE-mediated sensitization and were considered as atopic patients, skin tests and RAST were negative in the remaining 16 children and they were diagnosed as having cow milk intolerance (CMI) Forty-three coeliac patients were included as a positive control group and 18 normal children as the negative control group. The atopic group showed normal values of sIL-2R (1,183 +/- 468 u/ml); however, it was increased in children with CMI (1,453 +/- 469 u/ml, p0.05). The sIL-2R mean value was highest in patients with gastrointestinal symptoms (1,458 +/- 461 u/ml, p: 0.03) and the presence of atopic dermatitis was not relevant. The sIL-2R was also elevated in 8 children with igE-mediated sensitization against cow's milk (1,477 +/- 328 u/ml, p0.05). These results suggest that a delayed cellular mechanism occurred in CMI, similar to that present in coeliac disease, although it was less severe. In addition, there is an overlap of humoral and cellular immunological mechanisms in the IgE-mediated sensitization to cow's milk, but we did not find this coincidence in the allergy to remaining foods. From a pathogenic point of view, to separate CMI from IgE-mediated allergies to milk does not seem to be sufficiently justified at the present time. It is possible that the atopy against cow milk proteins in children has a different immunological mechanism than the atopy to other foods, which would explain its better prognosis.

The anti-tetanus serology was studied in Valladolid during 1988. IgG-antibodies and every one of four IgG-subclasses were determined by ELISA in 144 sera. In this study were included 31 parturient women, 20 newborn, 68 children 1.5-14 years old and 25 younger than 18 months. A 0.01 UI/ml sensibiling and a 8.5% interassay variability coefficient were achieved. The highest mean antibodies level (70.9-39.6 Ua/ml) was presented by children 1.5-3 years old and the lowest (31.1 +/- 15.9 Ua/ml) by 3-5 years old; nevertheless in mothers it was only 1.0 +/- 1.6 Ua/ml. Among children 1.5-14 years old we found only 5/63 (7.9%) cases with non-protective antibodies level. On the contrary, in mothers it increased until 23/31 (74%) and until 16/20 (80%) in cord blood. Antibodies of four IgG subclasses has each other a good correlation, especially IgG1/G2/G4 (p less than 0.001). The IgG2 and IgG3 subclasses were the antibodies which lesser decreased after vaccination. We emphasize the poor anti-tetanus protection of mothers and newborns, lower than levels reported in other countries.