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Overall survival of patients with Nijmegen breakage syndrome depending on the time when they were treated due to malignancies: before and after 2000 year.

The dynamics of primary cancer incidence among patients with NBS described using the three-stage joint-point model.

Overall survival of patients with Nijmegen breakage syndrome after cancer diagnosis. Patients who underwent HSCT were marked with an asterix.

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Purpose: Nijmegen breakage syndrome (NBS) is a DNA repair disorder with a high predisposition to hematologic malignancies. Experimental Design: We describe the natural history of NBS, including cancer incidence, risk of death, and the potential effectiveness of hematopoietic stem cell transplantation (HSCT) in preventing both pathologies: malignancy and immunodeficiency. Results: Among 241 patients with NBS enrolled in the study from 11 countries, 151 (63.0%) patients were diagnosed with cancer. Incidence rates for primary and secondary cancer, tumor characteristics, and risk factors affecting overall survival (OS) were estimated. The cumulative cancer incidence was 40.21% ± 3.5% and 77.78% ± 3.4% at 10 years and 20 years of follow-up, respectively. Most of the tumors n = 95 (62.9%) were non-Hodgkin lymphomas. Overall, 20 (13.2%) secondary malignancies occurred at a median age of 18 (interquartile range, 13.7–21.5) years. The probability of 20-year overall survival (OS) for the whole cohort was 44.6% ± 4.5%. Patients who developed cancer had a shorter 20-year OS than those without malignancy (29.6% vs. 86.2%; P < 10−5). A total of 49 patients with NBS underwent HSCT, including 14 patients transplanted before malignancy. Patients with NBS with diagnosed cancer who received HSCT had higher 20-year OS than those who did not (42.7% vs. 30.3%; P = 0.038, respectively). In the group of patients who underwent preemptive transplantation, only 1 patient developed cancer, which is 6.7 times lower as compared with nontransplanted patients [incidence rate ratio 0.149 (95% confidence interval, 0.138–0.162); P < 0.0001]. Conclusions: There is a beneficial effect of HSCT on the long-term survival of patients with NBS transplanted in their first complete remission of cancer.

Introduction: Hypersensitivity to ionising radiation is most often observed in the course of primary immunodeficiency diseases, which are associated with dysfunctional DNA repair, especially with the repair of double-strand breaks. Due to phenotypic similarities between primary immunodeficiency diseases, radiosensitivity testing can prove useful in early differential diagnosis, when attempting to identify patients with increased toxic reactivity to radio- and chemotherapy, and can have an impact on the process of their preparation for stem cell transplantation. Aim: The aim of the study was to assess the radiosensitivity in vitro of patients with ataxia-telangiectasia (A-T) syndrome, and their parents, carriers of one copy of the mutated ATM gene. Material/Methods: Lymphoblastoid cell lines (LCLs) from 15 A-T patients (remaining under the care of the Immunology Clinic and Immunology Outpatient Clinic of the Children’s Memorial Health Institute) and 11 mothers and 11 fathers of A-T patients, were used for radiosensitivity assessment. A standard colony survival assay (CSA) was applied in the tests. Results: A markedly decreased survival fraction (SF) of LCLs after in vitro exposure to X-rays was observed in all A-T patients when compared to control cells. A clear diversification of radiosensitivity to ionising radiation was observed among obligate heterozygotes. SF for heterozygotes was between 1% and 53%, i.e. varied from the values in healthy individuals to the extreme values observed in A-T patients. Conclusion: The assessment of cell radiosensitivity in A-T patients using CSA may be a useful additional test for confirming a clinically suspected disease. In heterozygous carriers, it can be an indicator of increased risk of carcinogenesis, and in both A-T patients and their parents can be helpful in making decisions with regard to radio- and/or chemotherapy.

Primary Immunodeficiencies (PNO) are a group of about 300 genetic disorders which result from the absence or dysfunction of the major components of the immune system. Among them an important subgroup constitute deficiencies associated with defects in DNA double strand breaks (DSBs) recognition and repair. These are primarily radiation-sensitive severe combined immune deficiencies (SCIDs) and combined immune deficiencies (CIDs) associated with genetic defects in the DNA-repair genes, which encode proteins necessary for T-cell and B cell maturation/differentiation. Due to increased risk of developing malignant neoplasms, mainly from hematopoietic origin, and over-reaction to standard anticancer radiotherapy and chemotherapy, treatment of these patients is a real challenge for clinicians. Clinical and laboratory manifestations, which may indicate increased radiosensitivity include: microcephaly, telangiectasias, lymphopenia, and translocation of chromosomes 7 and 14 in karyotype. A basic test showing increased radiosensitivity of lymphoblastoid cells lines or skin fibroblasts is percentage evaluation of their survival after exposition to ionizing radiation. Treatment of patients with impaired DNA repair depends on the clinical picture, immunological findings and type of immunodeficiency. Patients with SCID require immediate hematopoietic stem cell transplantation (HSCT) using reduced intensity conditioning (RIC). In patients with CID, standard treatment regimens require modification and/or avoidance of radiotherapy and some radiomimetic agents.

The retrospective analysis of a immunological and clinical survey in 33 boys with definitive diagno sis of X-linked agammaglobulinemia, based on ESID criteria, is presented. Recurrent lower respiratory tract infections were the most common presentation with the onset at the age of 1 year 3 months, when maternal antibodies disappeared. The clinical diagnosis was usually delayed by 2 years and 6 months. The mean IgG level at diagnosis was 1.03 g/l (range 0-4.0 g/l). Mean IgA was 0.039 g/l (range 0-0.38 g/l) and IgM – 0.189 g/l (range 0.021-3.51 g/l). The total number of B cells was decreased and varied between 0-391 cells/µl, with the mean value of 26 cells/µl and 0.65%. The replacement therapy with intra venous immunoglobulin (IVIG) preparation was also delayed, and introduced at the mean age of 3 years 5 months. In some patients it was followed with subcutaneous immunoglobulin (SCIG). The overall prog nosis in XLA patients is good if diagnosis and immunoglobulin replacement therapy are done early before the onset of chronic complications. Diagnosis was established through molecular analysis.

The aim of this study was to evaluate the serotype-specific pneumococcal status of children and adolescents with inflammatory bowel disease (IBD) who were naïve to pneumococcal vaccination before administering the 13-valent pneumococcal conjugate vaccine (PCV 13). This was an open, prospective study on children and adolescents aged 5–18 years who had IBD and were naïve to pneumococcal vaccination. A single dose of PCV 13 was administered to each patient. The geometric mean concentrations (GMCs) were measured for all 13 serotypes. A total of 122 subjects completed the study. Prevaccination GMCs ranged from 0.55 μg/ml (serotype 4) to 4.26 μg/ml (serotype 19A). Prior to the administration of PCV 13, high GMCs were detected in older children and adolescents who had IBD and were naïve to pneumococcal vaccination.

Nijmegen breakage syndrome (NBS) is a severe chromosomal instability disorder characterized by microcephaly, growth retardation, immune deficiency, and predisposition for malignancy. It is caused by hypomorphic mutations in the NBN gene, which product belongs to the protein complex critical for processing DNA double-strand breaks during mitotic and meiotic recombination. Data on gonadal function in patients with NBS are limited.Growth and sexual development, along with hormonal assays, were evaluated in girls and young women with NBS homozygous for c.657_661del5 mutation.The group comprised 37 girls and young women with NBS (ages, 0.17-24.25 yr), followed between 1993 and 2008. Patients were divided into three age groups: 1) 1-3 yr; 2) 4-9 yr; and 3) 10 yr and older. Growth, puberty, concentrations of gonadotropins and 17-beta-estradiol, bone age, and pelvic ultrasound were assessed.None of the patients presented a typical growth spurt; the adult height ranged between the 3rd and 25th centiles. Median bone age was delayed by 4.05 yr. Pubarche reached stadium P2 in eight patients and P3 in two patients. In all but one girl, thelarche did not exceed Th2, with low 17beta-estradiol levels. Gonadotropin levels showed a biphasic pattern, with median FSH values of 55.0, 10.9, and 81.9 IU/liter, and LH of 3.2, 0.8, and 21.0 IU/liter in consecutive age groups. Ultrasound visualized small ovaries or solid streaks and the hypoplastic uterus.Primary ovarian insufficiency and the associated hypergonadotropic hypogonadism are hallmark manifestations in girls and young women with NBS. Our findings emphasize the need for long-term endocrinological and interdisciplinary supervision of these patients.

The IgG subclass distribution of antibody to hepatitis B surface antigen (anti-HBs) was investigated in 19 children with chronic active hepatitis B infection who showed a complete serological seroconversion after interferon-a therapy. Determinations were done 6 and 12 months after treatment. Our results showed no selectivity in anti-HBs synthesis among IgG subclasses. All 4 IgG isotypes were involved in the response, with similar percentage contributions, on average, of IgG1 (35%), IgG3 (27%), and IgG4 (28%), followed by IgG2 (10%). IgG4 became the second most dominant isotype at the end of observation. These results are in contrast to those found after natural seroconversion, in which anti-HBs was highly restricted to neutralizing IgG1 and IgG3, with only a minor contribution from IgG2 and IgG4. It is postulated that analysis of the specific profiles of IgG subclasses may be of value for the estimation of the therapeutic efficacy of recombinant interferon-a used and may be helpful in choosing more-effective treatment. Chronic infection with hepatitis B (HB) virus can occur in children at any age and may lead to chronic hepatitis, liver cirrhosis, or hepatocellular carcinoma during childhood or adulthood [1]. Suppression of viral replication and modulation of the immune responses can prevent disease progression and decrease the severity of liver damage. Thus, the development of an effective therapy against HB virus infection seems to be a high priority. Interferon (IFN)‐a, a molecule that combines antiviral properties with the capacity to modulate the cellular immune response by its effects on the cytokine network [2], was proposed for the treatment of chronic HB »20 years ago [3]. Although its therapeutic use as an antiviral drug has increased significantly in recent years, a complete seroconversion

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. Due to a founder mutation in the underlying NBN gene (c.657_661del5) the disease is encountered most frequently among Slavic populations. The principal clinical manifestations of the syndrome are: microcephaly, present at birth and progressive with age, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism. Combined cellular and humoral immunodeficiency with recurrent sinopulmonary infections, a strong predisposition to develop malignancies (predominantly of lymphoid origin) and radiosensitivity are other integral manifestations of the syndrome. The NBN gene codes for nibrin which, as part of a DNA repair complex, plays a critical nuclear role wherever double-stranded DNA ends occur, either physiologically or as a result of mutagenic exposure. Laboratory findings include: (1) spontaneous chromosomal breakage in peripheral T lymphocytes with rearrangements preferentially involving chromosomes 7 and 14, (2) sensitivity to ionizing radiation or radiomimetics as demonstrated in vitro by cytogenetic methods or by colony survival assay, (3) radioresistant DNA synthesis, (4) biallelic hypomorphic mutations in the NBN gene, and (5) absence of full-length nibrin protein. Microcephaly and immunodeficiency are common to DNA ligase IV deficiency (LIG4 syndrome) and severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation due to NHEJ1 deficiency (NHEJ1 syndrome). In fact, NBS was most commonly confused with Fanconi anaemia and LIG4 syndrome. Genetic counselling should inform parents of an affected child of the 25% risk for further children to be affected. Prenatal molecular genetic diagnosis is possible if disease-causing mutations in both alleles of the NBN gene are known. No specific therapy is available for NBS, however, hematopoietic stem cell transplantation may be one option for some patients. Prognosis is generally poor due to the extremely high rate of malignancies. Zespół Nijmegen (Nijmegen breakage syndrome; NBS) jest rzadkim schorzeniem z wrodzoną niestabilnością chromosomową dziedziczącym się w sposób autosomalny recesywny, charakteryzującym się przede wszystkim wrodzonym małogłowiem, złożonymi niedoborami odporności i predyspozycją do rozwoju nowotworów. Choroba występuje najczęściej w populacjach słowiańskich, w których uwarunkowana jest mutacją założycielską w genie NBN (c.657_661del5). Do najważniejszych objawów zespołu zalicza się: małogłowie obecne od urodzenia i postępujące z wiekiem, charakterystyczne cechy dysmorfii twarzy, opóźnienie wzrastania, niepełnosprawność intelektualną w stopniu lekkim do umiarkowanego oraz hipogonadyzm hipogonadotropowy u dziewcząt. Na obraz choroby składają się także: niedobór odporności komórkowej i humoralnej, który jest przyczyną nawracających infekcji, znaczna predyspozycja do rozwoju nowotworów złośliwych (zwłaszcza układu chłonnego), a także zwiększona wrażliwość na promieniowanie jonizujące. Wyniki badań laboratoryjnych wykazują: (1) spontaniczną łamliwość chromosomów w limfocytach T krwi obwodowej, z preferencją do rearanżacji chromosomów 7 i 14, (2) nadwrażliwość na promieniowanie jonizujące lub radiomimetyki, co można wykazać metodami in vitro, (3) radiooporność syntezy DNA, (4) hipomorficzne mutacje na obu allelach genu NBN, oraz (5) brak w komórkach pełnej cząsteczki białka, nibryny. Małogłowie i niedobór odporności występują także w zespole niedoboru ligazy IV (LIG4) oraz w zespole niedoboru NHEJ1. Rodzice powinni otrzymać poradę genetyczną ze względu na wysokie ryzyko (25%) powtórzenia się choroby u kolejnego potomstwa. Możliwe jest zaproponowanie molekularnej diagnostyki prenatalnej jeżeli znane są obie mutacje będące przyczyną choroby. Nie ma możliwości zaproponowania specyficznej terapii, ale przeszczep szpiku może być alternatywą dla niektórych pacjentów. Generalnie prognoza nie jest pomyślna z uwagi na wysokie ryzyko rozwoju nowotworu.

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar degeneration, immunodeficiency, oculocutaneous telangiectasias, chromosomal instability, radiosensitivity, and cancer predisposition. The gene mutated in the patients, ATM, encodes a member of the phosphatidylinositol 3-kinase family proteins. The ATM protein has a key role in the cellular response to DNA damage. Truncating and splice site mutations in ATM have been found in most patients with the classical AT phenotype. Here we report of our extensive ATM mutation screening on 25 AT patients from 19 families of different ethnic origin. Previously unknown mutations were identified in six patients including a new homozygous missense mutation, c.8110T > C (p.Cys2704Arg), in a severely affected patient. Comprehensive clinical data are presented for all patients described here along with data on ATM function generated by analysis of cell lines established from a subset of the patients.

The Nijmegen breakage syndrome (NBS) is a rare inherited condition, characterized by microcephaly, radiation hypersensitivity, chromosomal instability, an increased incidence of (mostly) lymphoid malignancies, and immunodeficiency. NBS is caused by hypomorphic mutations in the NBN gene (8q21). The NBN protein is a subunit of the MRN (Mre11-Rad50-NBN) nuclear protein complex, which associates with double-strand breaks. The immunodeficiency in NBS patients can partly be explained by strongly reduced absolute numbers of B lymphocytes and T lymphocytes. We show that NBS patients have a disturbed precursor B-cell differentiation pattern and significant disturbances in the resolution of recombination activating gene-induced IGH breaks. However, the composition of the junctional regions as well as the gene segment usage of the reduced number of successful immunoglobulin gene rearrangements were highly similar to healthy controls. This indicates that the NBN defect leads to a quantitative defect in V(D)J recombination through loss of juxtaposition of recombination activating gene-induced DNA ends. The resulting reduction in bone marrow B-cell efflux appeared to be partly compensated by significantly increased proliferation of mature B cells. Based on these observations, we conclude that the quantitative defect will affect the B-cell receptor repertoire, thus contributing to the observed immunodeficiency in NBS patients.

Introduction Hereditary angioedema (HAE) is caused by mutations in the C1inh gene, leading to dysfunction of the C1-esterase inhibitor (C1-INH). C1-INH interacts with MASP-1 and MASP-2 proteases, participating in the mannan-binding lectin (MBL) pathway of complement activation. The aim of the study was to investigate the contribution of possible changes in MBL/MASP-2 complex activity and Helicobacter pylori, hepatitis B virus (HBV), and hepatitis C virus (HCV) infections to the severity and frequency of clinical symptoms of HAE. Materials and Methods The study was performed in 65 patients with HAE and 113 healthy persons. The parameters measured were C1-INH, C4, MBL concentration and MBL/MASP-2 complex activity, and serological markers of H. pylori, HBV, and HCV infection. Scores for the frequency and severity of HAE symptoms were determined. Results HAE scores were significantly higher in patients whose C1-INH activity did not exceed 10% than in patients with activity of 10-52% (p=0.016). No significant differences were found in the median levels of MBL concentration and MBL/MASP-2 complex activity between patients and the control group. There was a slight association between contact with H. pylori in patients and HAE symptom score (p=0.052, not significant). Adult patients showed a 2.6-times higher frequency of anti-HBc than the general population. HBV DNA was negative in anti-HBc(+) patients. Conclusions These results suggest that the MBL complement activation pathway itself does not contribute to the frequency of angioedema attacks. Infections with H. pylori and HBV may slightly influence the disease score (not significant).

The aim of our study was to assess: (1) whether seroconversion to IgG anti-HBs, induced by IFN-alpha therapy in children with chronic active hepatitis B, is maintained 4-10 years after treatment; and (2) whether HBV-DNA is present in circulation despite the synthesis of anti-HBs.Serum samples were collected from 38 patients and serological markers of HBV were determined in each of them. HBV-DNA was determined by PCR in anti-HBs positive sera. Serum samples obtained from 19 subjects with a complete spontaneous seroconversion after acute HBV served as controls.Four to 10 years after therapy, anti-HBs were present in ca. 97.4% patients with GMT value of 775 IU/L vs 127 IU/L found in controls. HBsAg was found in 2/38 subjects. In 13 out of 37 patients (35.1%) free and/or bound HBV-DNA was present.This study showed that seroconversion induced by IFN-alpha may not be a sustained phenomenon. HBV-DNA may persist for a long time after therapy despite the anti-HBs synthesis.

This review deals with the diagnostics of immunoglobulin defects. The development of methods used to detect and quantitate concentrations of immunoglobulins and their subclasses was shortly discussed; following by the role of antibodies in the host defence. Seven out of the ten main immunodeficiencies with the prevalence of antibody defects were then delineated. The diagnostics of humoral immunodeficiencies was illustrated by the example of three boys with hypogammaglobulinemia and three children with common variable immunodeficiency. Percentages of B lymphocytes varied, independent with the very decreased concentrations of immunoglobulin. Concentrations of IgG, IgA, IgM, IgE and IgG subclasses in healthy children of ages from birth to 16 years, were presented in the tables.

Item does not contain fulltext Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by spontaneous chromosomal instability with predisposition to immunodeficiency and cancer. In order to assess the cellular basis of the compromised immune response of NBS patients, the distribution of functionally distinct lymphocyte subsets in peripheral blood was evaluated by means of double-colour flow cytometry. The study involved the 36 lymphopenic patients with a total lymphocyte count < or =1500 microl (group A) and seven patients (group B) having the absolute lymphocyte count comparable with the age-matched controls (> or =3000 microl). Regardless of the total lymphocyte count the NBS patients showed: (1) profound deficiency of CD4+ and CD3/CD8+ T cell subsets and up to fourfold increase in natural killer (NK) cells, almost lack of naive CD4+ T cells expressing CD45RA isoform, unchanged percentage of naive CD8+ cell subset (CD8/CD45RA+) but bearing the CD8 receptor of low density (CD8low); (2) normal expression of CD45RA isoform in the CD56+ lymphocyte subset, profound decrease in alpha beta but up to threefold increase in gamma delta-T cell-receptor (TCR)-positive T cells; (3) shift towards the memory phenotype in both CD4+ and CD8+ lymphocyte subpopulations expressing CD45RO isoform (over-expression of CD45RO in terms of both the fluorescence intensity for CD45RO isoform and the number of positive cells); and (4) an increase in fluorescence intensity for the CD45RA isoform in NK cells population. These results indicate either a failure in T cell regeneration in the thymic pathway (deficiency of naive CD4+ cells) and/or more dominant contribution of non-thymic pathways in lymphocyte renewal reflected by an increase in the population of CD4+ and CD8+ memory cells, gamma delta-TCR positive T as well as NK cell subsets.

Summary During an 8-year period of observation, defects of immune responses were characterized and monitored in 40 of 50 Polish children with Nijmegen breakage syndrome referred to the Children's Memorial Health Institute in Warsaw. The following parameters were determined at diagnosis: (1) concentrations of serum IgM, IgG, IgA; (2) concentrations of IgG subclasses; and (3) lymphocyte subpopulations. In addition, naturally acquired specific antibodies against Streptococcus pneumoniae were determined in 20 patients with a history of recurrent respiratory infections. During follow-up, total serum immunoglobulins and IgG subclasses were monitored systematically in 17 patients who did not receive immunomodulatory therapy. Moreover, anti-HBs antibody response was measured after vaccination of 20 children against HBV. We found that the immune deficiency in NBS is profound, highly variable, with a tendency to progress over time. Systematic monitoring of the humoral response, despite good clinical condition, is essential for early medical intervention.

Ataxia-Telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are recessive genetic diseases with similar cellular phenotypes that are caused by mutations in the recently described ATM (encoding ATM) and NBS1 (encoding p95) genes, respectively. Both disorders are accompanied by immunodeficiency in a majority of patients, but the mechanism involved has as yet not been established. We demonstrate that in cells from A-T patients, the switch (S) recombination junctions are aberrant and characterized by a strong dependence on short sequence homologies and devoid of normally occurring mutations around the breakpoint. A low number of S fragments were generated in cells from NBS patients and showed only limited dependence on sequence identity and mutation frequencies were similar to those observed in normal controls. We propose that ATM and p95 are both involved in the final step(s) in class switch recombination with related, but disparate, functional roles. Thus, the general pathway involved in DNA repair also has a major influence on the immunoglobulin isotype switching process.

Common variable immune deficiency (CVID) is a heterogeneous disease associated with ineffective production of antibodies. It is usually diagnosed in adulthood, but a variable proportion of children develop CVID. Early identification of patients with potentially worse prognosis may help to avoid serious complications. The goal of this study was to associate the clinical phenotype of patients with early onset CVID with peripheral B-cell maturation profile. Four color flow cytometry was used to define distribution of peripheral B-cell subsets in 49 children with early-onset CVID. All clinical data were extracted from medical records. A proportion of patients demonstrated diminishing with time total B-lymphocytes pool, beyond physiological age-related changes. Irrespective from duration of the follow-up period the B-cell maturation profile in individual patients remained unchanged. We identified six different aberrant peripheral B cell maturation profiles associated with different clinical characteristics. Patients with an early B-cell maturation block earlier required replacement therapy and were at significantly greater risk of enteropathy, granuloma formation, cytopenia, and lymphoproliferation. B-cell maturation inhibited at the natural effector stage was associated with higher risk of autoimmune manifestations other than autoimmune cytopenia. Prevalence of male patients was observed among patients with B-cell maturation inhibited at naive B-cell stage. In conclusion, the diagnostic process in patients with suspected early-onset CVID shall include routine analysis of peripheral B-cell maturation to provide surrogate markers identifying patients at greater risk of developing certain complications.

BACKGROUND There are only a few studies on immune response to pneumococcal vaccines in patients with inflammatory bowel disease (IBD); all of them assessed polysaccharide vaccines only. The aim of the study was to evaluate the immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) in IBD pediatric patients compared with healthy controls. METHODS This was a multicenter, prospective, and controlled study on children and adolescents aged 5 to 18 years with IBD with no history of pneumococcal immunization. The subjects for the study belonged to one of the following groups: patients with IBD on no immunosuppressive therapy (group A), those on tumor necrosis factor agents or immunomodulators (group B), and healthy controls (group C). The study population received 1 intramuscular injection of PCV13. The primary outcome measure was adequate vaccine response defined as postvaccination titer ≥0.35 μg/mL to all 13 serotypes. Geometric mean titers and geometric mean titer rises were measured for all serotypes. The evidence of local and systemic adverse effects for 5 days after the vaccine was registered. RESULTS A total of 178 subjects (122 patients and 56 controls) completed the study course. There was no significant difference in the rate of adequate vaccine response between patients with IBD and controls measured 4 to 8 weeks after vaccination (90.4% versus 96.5%, P = 0.5281). Children in group A had higher geometric mean titer rises than children in group B (P = 0.0369). There were no serious adverse events related to PCV13 during the study. CONCLUSIONS PCV13 is both immunogenic and safe in pediatric patients with IBD.