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Objectives: This study aims to uncover early detection markers through the immunological analysis of children diagnosed with multisystem inflammatory syndrome (MIS-C) and coronavirus disease-2019 (COVID-19)., Methods: We retrospectively analyzed immunological data from thirty-three MIS-C patients and an equivalent number of patients under the age of 18 with a positive polymerase chain reaction (PCR) test for COVID-19. These individuals were admitted to Ondokuz Mayis University between November 2020 and February 2021. In total, the study group consisted of 66 patients and an additional 10 healthy controls., Results: Lymphopenia, thrombocytopenia, anemia, and neutrophilia, along with elevated levels of ferritin, D-dimer, and C-reactive protein, were more pronounced in MIS-C patients (p<0.001). No significant disparities were found in serum IgG, A, M, and E concentrations. Notably, there was an increased proportion of B cells (p<0.001), an inversion of the CD4/CD8 ratio, and a marked presence of CD3+CD38+HLA-DR+active T cells (p=0.009) in the MIS-C cohort., Conclusion: In the early diagnosis of MIS-C, lymphopenia, increase in B cells, reversal of CD4/CD8 ratio, and demonstration of CD3+CD38+HLA-DR+active T cells may be helpful., Competing Interests: None declared., (© Copyright 2024 by The Medical Bulletin of Sisli Etfal Hospital.)

Purpose: Immunodeficiency with centromeric instability and facial anomalies (ICF) syndrome is a rare autosomal recessive combined immunodeficiency. The detailed immune responses are not explored widely. We investigated known and novel immune alterations in lymphocyte subpopulations and their association with clinical symptoms in a well-defined ICF cohort., Methods: We recruited the clinical findings from twelve ICF1 and ICF2 patients. We performed detailed immunological evaluation, including lymphocyte subset analyses, upregulation, and proliferation of T cells. We also determined the frequency of circulating T follicular helper (cT FH ) and regulatory T (Treg) cells and their subtypes by flow cytometry., Results: There were ten ICF1 and two ICF2 patients. We identified two novel homozygous missense mutations in the ZBTB24 gene. Respiratory tract infections were the most common recurrent infections among the patients. Gastrointestinal system (GIS) involvements were observed in seven patients. All patients received intravenous immunoglobulin replacement therapy and antibacterial prophylaxis; two died during the follow-up period. Immunologically, CD4 + T-cell counts, percentages of recent thymic emigrant T cells, and naive CD4 + T decreased in two, five, and four patients, respectively. Impaired T-cell proliferation and reduced CD25 upregulation were detected in all patients. These changes were more prominent in CD8 + T cells. GIS involvements negatively correlated with CD3 + T-, CD3 + CD4 + T-, CD16 + CD56 + NK-cell counts, and CD4 + /CD8 + T-cell ratios. Further, we observed expanded cT FH cells and reduced Treg and follicular regulatory T cells with a skewing to a T H 2-like phenotype in all tested subpopulations., Conclusion: The ICF syndrome encompasses various manifestations affecting multiple end organs. Perturbed T-cell responses with increased cT FH and decreased Treg cells may provide further insight into the immune aberrations observed in ICF syndrome., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA -/- ) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4 +/- ) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown., Objective: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up., Methods: The 98 patients (63 LRBA -/- and 35 CTLA4 +/- ) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies., Results: The LRBA -/- patients exhibited a more severe disease course than did the CTLA4 +/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA -/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival., Conclusions: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Peripheral nerve injury is common and negatively affects an individual's quality of life. Drugs used for peripheral nerve regeneration should aim to eliminate symptoms such as neuropathic pain and have therapeutic effects. In recent studies, pigment epithelium-derived factor (PEDF) has been considered an essential therapeutic agent because of its potential neuroprotective properties. In this study, we aimed to investigate the efficacy of locally applied PEDF for peripheral nerve regeneration. Twenty-four Wistar albino male rats were used. The study groups included Injury (n = 12) and Injury+PEDF (n = 12). An injury model was created by applying 50 N pressure to the right sciatic nerves in groups, and 10 μg/kg local PEDF was injected into the Injury+PEDF group. After 28 days of recovery, functional tests and stereological, immunohistochemical, and biochemical analyses were performed. A significant difference was found between the Injury and Injury+PEDF groups in amplitude, whereas no difference was found in latency. The number of myelinated axons and the myelinated axon area increased significantly in the Injury+PEDF group, while no statistically significant difference was found in myelin sheath thickness. Superoxide dismutase, catalase, and glutathione peroxidase activities were increased by PEDF, whereas they were suppressed in mesenchymal stem cells. PEDF exerts functional, quantitative, and antioxidative effects on sciatic nerve injury during neuroregeneration. In addition, when oxidative stress parameters were examined, it was seen that PEDF reduced oxidative stress following sciatic nerve injury., (© 2023 American Association for Anatomy.)

Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28., (© 2022 Lévy et al.)

Background: Lipopolysaccharide-responsive beige-like anchor protein (LRBA) deficiency and cytotoxic T-lymphocyte protein-4 (CTLA-4) insufficiency are recently described disorders that present with susceptibility to infections, autoimmunity, and lymphoproliferation. Clinical and immunological comparisons of the diseases with long-term follow-up have not been previously reported. We sought to compare the clinical and laboratory manifestations of both diseases and investigate the role of flow cytometry in predicting the genetic defect in patients with LRBA deficiency and CTLA-4 insufficiency., Methods: Patients were evaluated clinically with laboratory assessments for lymphocyte subsets, T follicular helper cells (T FH ), LRBA expression, and expression of CD25, FOXP3, and CTLA4 in regulatory T cells (Tregs) at baseline and 16 h post-stimulation., Results: LRBA-deficient patients (n = 29) showed significantly early age of symptom onset, higher rates of pneumonia, autoimmunity, chronic diarrhea, and failure to thrive compared to CTLA-4 insufficiency (n = 12). In total, 29 patients received abatacept with favorable responses and the overall survival probability was not different between transplanted versus non-transplanted patients in LRBA deficiency. Meanwhile, higher probability of survival was observed in CTLA-4-insufficient patients (p = 0.04). The T-cell subsets showed more deviation to memory cells in CTLA-4-insufficiency, accompanied by low percentages of Treg and dysregulated cT FH cells response in both diseases. Cumulative numbers of autoimmunities positively correlated with cT FH frequencies. Baseline CTLA-4 expression was significantly diminished in LRBA deficiency and CTLA-4 insufficiency, but significant induction in CTLA-4 was observed after short-term T-cell stimulation in LRBA deficiency and controls, while this elevation was less in CTLA-4 insufficiency, allowing to differentiate this disease from LRBA deficiency with high sensitivity (87.5%) and specificity (90%)., Conclusion: This cohort provided detailed clinical and laboratory comparisons for LRBA deficiency and CTLA-4 insufficiency. The flow cytometric approach is useful in predicting the defective gene; thus, targeted sequencing can be conducted to provide rapid diagnosis and treatment for these diseases impacting the CTLA-4 pathway., (© 2022 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Aim of this study is to investigate effects of stem cells derived from the peripheral nerve and adipose tissues following the nerve crush injury in control and obese rats. For this aim, 41 Wistar Albino female rats were separated into eight equal groups; non-obese control (NOC) obese control (OC), non-obese injury (NOH), obese injury (OH), non-obese adipose (NOY), obese adipose (OY), non-obese nerve (NOPS), obese nerve (OPS). At the end of 8 weeks, all experimental animals without control groups were subjected to nerve crush procedure and sciatic nerve or fat stem cell homogenates were injected on the treatment group rats, and then, recovery process has been observed and histopathological, stereological, electrophysiological analyses and bioinformatic evaluation were made on removed sciatic nerves. Stereological results showed that adipose homogenate gave more successful results than peripheral nerve homogenates in the NOY group in comparison to the NOPS group in terms of myelinated axon number. Peripheral nerve homogenate has shown more successful results in the OPS group in comparison to the OY group. The number of unmyelinated axons was increased following treatment with adipose tissue homogenate in NOY and OY groups. In terms of myelin sheath thickness; we detected that treatments by peripheral nerve and especially adipose tissue homogenates lead to increase in the thickness of the axons of the peripheral nerves belong to the control and obese injury groups. All results showed that mesenchymal stem cell treatment by fresh tissue homogenates is successful in peripheral nerve regeneration and fat tissue is a considerable source of the stem cells for clinical applications.

Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various genetic causes, and if it remains untreated, patients succumb to infections during the first 2 years of life., Purpose and Methods: This study reported retrospective data from 72 infants diagnosed with SCID including their major clinical features, HSCT characteristics, and outcomes over a 20-year period (1997-2017)., Results: Sixty-one of 72 SCID patients in the study underwent HSCT from 1997 to 2017. Median ages at the time of diagnosis and transplantation were 3.5 months and 5 months, respectively. Consanguinity was present in 68% of the patients, and T - B - NK + phenotype was predominantly identified. The overall survival was 80.3% over a 20-year period. However, the patients transplanted during an active infection had a lower survival rate of 73.9% compared to 100% for patients transplanted infection-free or with a previous infection that had resolved. The survival rate was significantly higher among recipients of HLA-identical transplants (92.9%), compared to recipients of mismatched related transplants (70%). The overall survival increased from 50 (1997-2006) to 85% (2007-2017) during the last 10 years., Conclusions: This is one of the largest single-center studies in Turkey with extensive experience about SCID patients. Early diagnosis of SCID patients before the onset of an infection and early transplantation are shown to be extremely important factors affecting the outcome and increasing the survival regardless of the donor type based on the results of this study., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients with autosomal recessive protein kinase C δ (PKCδ) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also suffer from recurrent infections that overlap with those seen in patients with chronic granulomatous disease (CGD), a disease caused by defects of the phagocyte NADPH oxidase and a lack of reactive oxygen species (ROS) production. We studied an international cohort of 17 PKCδ-deficient patients and found that their EBV-B cells and monocyte-derived phagocytes produced only small amounts of ROS and did not phosphorylate p40phox normally after PMA or opsonized Staphylococcus aureus stimulation. Moreover, the patients' circulating phagocytes displayed abnormally low levels of ROS production and markedly reduced neutrophil extracellular trap formation, altogether suggesting a role for PKCδ in activation of the NADPH oxidase complex. Our findings thus show that patients with PKCδ deficiency have impaired NADPH oxidase activity in various myeloid subsets, which may contribute to their CGD-like infectious phenotype., Competing Interests: Disclosures: P.A. Brogan reported personal fees from Sobi, Novartis, Roche, and GSK, and grants from Sobi outside the submitted work. No other disclosures were reported., (© 2021 Neehus et al.)

Objectives: Severe combined immunodeficiency disease (SCID), non-SCID T-cell lymphopenia, and other primary immunodeficiency diseases with T-cell and B-cell lymphopenia have low the T-cell-receptor-excision circles (TRECs) and κ-deleting-recombination-excision circles (KRECs) levels that can be measured in dried blood spots (DBS) of the newborn. The incidence of SCID and non-SCID T-cell lymphopenia in Western societies has been reported by TREC screening of newborns as 1: 58,000 and 1: 7300, respectively. Since there is no similar study in our country, we aimed to perform the first pilot study of TREC and KREC screening of newborn for SCID and non-SCID T-cell lymphopenia in Turkey., Methods: The heel blood samples of newborns born between 1st October 2015 and 31st December 2016 at two major hospitals in our city were included in this study. TREC and KREC copies were determined by a multiplex quantitative PCR-based method from newborn DBS. Cutoff levels were used as 7 copies per DBS for TRECs and KRECs, 1000 copies for ACTB (internal control). Failed samples or abnormal results in measurements were tested the second time. An immunologist evaluated data of newborns with low TREC and KREC copies clinically and through the laboratory., Results: A total of 1960 DBS were tested. The results of 1856 newborns were evaluated. The low TRECs and/or KRECs levels were detected in 71 newborns (3.8 %). The low TRECs rate was 1.1 %. Preterm newborns have lower levels of TRECs and KRECs than term newborns (both p <0.0001). As a result of immunological research, we did not detect any SCID, but we detected 2 newborns with non-SCID T-cell lymphopenia (1:928). These 2 newborns were found to have frequent and severe infectious diseases or hypogammaglobulinemia in their clinical follow-up, although they did not have absolute lymphopenia., Conclusion: Non-SCID T-cell lymphopenia is common in our country than in western societies. TRECs and KRECs assay should be considered for routine NBS programs in our country. Studies involving more newborns should be conducted to detect SCID., (Copyright © by The Medical Bulletin of Sisli Etfal Hospital.)

Background: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder characterized by several motor and phonic tics., Aims: In this study, we aimed to compare activated regulatory T cell (Treg) values between patients with TS/chronic tic disorder (CTD) and age- and sex-matched healthy controls (HCs)., Materials and Method: Patients with TS/CTD and age- and sex-matched HCs were included in the study. The severity of the disease was evaluated using the Yale Global Tic Severity Scale. CD4 + CD25 + CD127 low Tregs from the patient group and the control group were compared using flow cytometry., Results: The study included 48 patients diagnosed with TS/CTD (36 males and 12 females, mean age: 11.58 ± 2.61) and 24 HCs (18 males and 6 females, mean age: 11.63 ± 2.60). The TS/CTD group had significantly higher activated regulatory T percentile with respect to the T helper value compared to the HCs ( p =  0.010). Lymphocyte count, T lymphocyte count, T lymphocyte percentage, T-helper lymphocyte count, and T-helper lymphocyte percentage were lower in the patient group compared to the control group ( p =  0.024, 0.003, 0.007, <0.001, <0.001, respectively). The comparison of three groups (mild, moderate-severe, and HCs) revealed that T lymphocyte number and percentage and the T helper number and percentage were significantly higher in the HC group compared to the moderate-severe group, whereas the activated Treg percentage with respect to the T helper value was significantly higher in the moderate-severe group compared to the HC group (0.002, 0.026, <0.001, <0.001, 0.027, respectively)., Conclusion: Our results suggest that Tregs may have a role in the pathogenesis of TS/CTD.

Background: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established., Objective: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations., Methods: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry., Results: The mean age of the patients was 13.4 ± 7.9 years, and the follow-up period was 3.4 ± 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy., Conclusions: Long-term abatacept therapy is effective in most patients with LRBA deficiency., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Severe combined immunodeficiency (SCID) is the most serious PID, characterized by T cell lymphopenia and lack of antigen-specific T cell and B cell immune responses, inevitably leading to death within the first year of life if hematopoietic stem cell transplantation (HSCT) is not performed., Purpose and Methods: Since SCID is a common type of PID with an estimated incidence of 1/10.000 in Turkey, a retrospective analysis of HSCT characteristics, survival, immune recovery, and the major clinical features of SCID prior to HSCT is the aim of this multi-transplant center-based analysis., Results: A total of 234 SCID patients transplanted between the years 1994 and 2014 were included in the study. Median age at diagnosis was 5 months, at transplantation, 7 months, B- phenotype and RAGs were the most common defects among others. Immune phenotype did not seem to have an effect on survival rate (p > 0.05), Immunoglobulin (Ig) requirement following HSCT did not differ between B+ and B- phenotypes (p > 0.05). Overall survival rate was 65.7% over a period of 20 years. It increased from 54% (1994-2004) to 69% (p = 0.052) during the last 10 years (2005-2014). Ten-year survival after HSCT has improved over time although the difference was not significant. Infection at the time of transplantation (p = 0.006), mismatched related donor (MMRD) (haploidentical parents), and matched unrelated donor (MUD) donor transplants p < 0.001 were the most important factors, significantly affecting the outcome., Conclusions: This is the first multicenter study with the largest data obtained from transplanted SCID patients in Turkey. Early diagnosis with newborn screening (NBS) together with emerging referrals, treatment by transplantation centers, and specialized teams are mandatory in countries with high parental consanguinity such as Turkey.

Ataxia-telangiectasia (A-T) is a multisystem disease caused by a genetic defect located on the long arm of chromosome 11 (11p22-23). The gene defect results in the loss of A-T-mutated protein, subsequently leading to unrepaired DNA fractures and defects in the signal transduction pathway. As a result, characteristic findings arise, including recurrent sinopulmonary infections, hypersensitivity against ionized radiation with the tendency to develop cancer related to progressive cerebellar ataxia, pathognomonic oculocutaneous telangiectasias, varying degrees of humoral and cellular immunodeficiency, and infertility. This case report presents a 3-year-old male patient with A-T who developed hemophagocytic syndrome. To the best of our knowledge, no such case has been previously reported.

Background: The purpose of this study is to examine the changes in B lymphocyte subsets in patients receiving allergen immunotherapy., Methods: B lymphocyte subsets of patients before immunotherapy and one year after immunotherapy began were examined using the flow cytometric method. Age-matched healthy children served as the control group., Results: Twenty-two patients with asthma and/or allergic rhinitis and 14 healthy, age-matched controls were included in the study. The median age of the patients was 13 years old (range: 6-20 years), and eleven (50.0%) were male. The median age of the healthy controls was also 13 years old (range: 7-17), and seven (50.0%) were male. In the age group from 11 to 15 years; the patients' relative and absolute counts of active and mature sensitive B cells were higher than those of the healthy children (p=0.027-0.012 and p=0.032-0.010, respectively) before immunotherapy. The relative and absolute counts of active B cells before immunotherapy were also significantly higher than those of after immunotherapy (p=0.001-0.001, p=0.025-0.037, and p=0.029-0.035, respectively). Before immunotherapy, the relative and absolute counts of mature sensitive B cells were significantly higher than those obtained after immunotherapy (p=0.024-0.006) in the 11-15-year-old age group., Conclusions: Allergen immunotherapy directly influences B cell differentiation and causes a decrease in the count of active B cells. This finding is relevant because the B cell count can be used as a guide in the assessment of an individual patient's treatment response and also when determining whether to continue the immunotherapy., (Copyright © 2017 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

ICF syndrome is a primary immunodeficiency disease characterized by hypo- or agammaglobulinemia, centromeric instability mainly on chromosomes 1, 9, and 16 and facial anomalies. ICF syndrome presents with frequent respiratory tract infections in infancy. A 20-month-old female patient was referred to our clinic due to frequent lower respiratory tract infections. ICF syndrome was considered because of comorbidity of hypogammaglobulinemia, facial anomalies, and neuromotor growth retardation. Metaphase chromosome analysis revealed centromeric instability on chromosomes 1, 9, and 16 and through Sanger a previously unreported homozygous missense mutation (c.1805T>C; [p.V602A]) was identified in the DNMT3B, confirming ICF1. The patient was found to have a breakdown in renal function 1 year later; the urinary system was examined and bilateral vesicoureteral reflux was found, warranting the need for dialysis in time. This report expands the mutation spectrum of ICF1 and is the first to describe bilateral vesicoureteral reflux accompanying ICF syndrome. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Purpose: Prematurity is the most common cause of infant mortality and morbidity. To prevent this, the timing of parturition and its mechanisms should be understood. It is likely that inhibitor CD94/NKG2A positive decidual natural killer cells (uNK) provide for the continuation of pregnancy. Here, we aimed to evaluate whether CD94/NKG2A positive uNK cells are highest in elective cesarian section (C/S) (suggesting ongoing gestation), moderate in normal full-term birth, and lowest in pre-eclamptic parturition., Methods: Of 48 pregnant women, 21 C/S, 16 normal, and 11 pre-eclamptic deliveries were included in this study. Five placentas in each group were assigned randomly. After staining, the volumetric analysis of the placental villi and villous blood vessels was performed via the Cavalieri principle. The CD94/NKG2A positive uNK cells were counted using the physical disector method., Results: The gestation periods and birth weights of the pre-eclamptic deliveries were lower than those of the other two groups. Additionally, the villi and villous vascular volumes were lowest in the pre-eclamptic placentas. As proposed in our hypothesis, the inhibitor CD94/NKG2A positive uNK cells were the highest in the C/S, moderate in the normal, and lowest in the pre-eclamptic placentas., Conclusions: These data suggest that CD94/NKG2A positive uNK cells are related with the continuation of pregnancy, and that our human model could be used to search for parturition-timing machinery. We believe that CD94/NKG2A positive uNK cells are also related to the timing of birth.

Background: The objective of this study was to examine the B lymphocyte subsets in primary immunodeficiency that progress with antibody deficiency., Methods: The patients' naive, memory, class-switched memory and non-switched memory B cells were compared with those of healthy individuals of matching ages using flow cytometry., Results: A total of 67 patients with antibody deficiency and 28 healthy children of matching ages were included in the study. The median age of the patients was six years (min-max: 1-24) and 40 (59.7%) were male. The median age of the healthy controls was again six years (min-max: 1-17) and 12 (42.8%) were male. Patients with common variable immunodeficiency had higher relative counts of naive cells when compared with the control group; however, they were found to have lower relative counts of memory, relative and absolute counts of non-switched and relative counts of switched B lymphocytes (p=0.001, 0.023, 0.003-0.003, 0.001, respectively). In patients with selective IgA deficiency, similar to patients with common variable immunodeficiency, the relative counts of naive cells were found to be higher, while the relative counts of memory and relative and absolute counts of non-switched B lymphocytes were found to be lower when compared with the control group (p=0.011, 0.032, 0.006-0.009, respectively). Although patients with selective IgM deficiency had higher relative counts of naive B cells when compared with the control group, they had lower relative and absolute counts of non-switched B lymphocytes (p=0.008-0.016)., Conclusions: The B lymphocyte subsets of patients with selective IgA deficiency are largely similar to those of patients with common variable immunodeficiency. Both illness groups exhibit low levels of memory B cells., (Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The cause and pathophysiology of PFAPA syndrome is unknown. The aim of this study was to determine all MEFV gene variants relevant to familial Mediterranean fever in children with PFAPA syndrome., Methods: All MEFV gene variants were analyzed in patients with PFAPA syndrome. All patients were evaluated using the Gaslini scoring system. Serum immunoglobulin levels were also determined upon admission., Results: We evaluated 64 patients with PFAPA syndrome. The median age at diagnosis was 37.5 (min-max: 6-96) months, and the percentage of male patients was 55.0%. The Gaslini diagnostic score for periodic fever was high in 81.0% of the patients. An MEFV gene mutation was found in 42 (66.0%) children. Mostly, heterozygous or compound heterozygous variants of the MEFV gene were found. Two patients were homozygous for R202Q. MEFV gene mutations were not detected in 22 (34.0%) patients. No significant differences in clinical or laboratory findings were observed between the two groups (p > 0.05), and there were no significant differences in period and duration of the fever episodes (p > 0.05). The fever of all 47 patients (100.0%) who received prednisolone during the episodes decreased within hours and did not recur. Eighteen of the patients using prednisolone underwent prophylaxis with colchicine, and the fever episodes of 9/18 (50.0%) patients using colchicine decreased within months., Conclusions: Most patients presenting with PFAPA syndrome have heterozygous MEFV gene mutations. Whether carrying a heterozygous MEFV gene is the primary cause of this syndrome requires further investigation., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To determine the proportion of children with herpes simplex encephalitis (HSE) displaying TLR3 deficiency, the extent of TLR3 allelic heterogeneity, and the specific clinical features of TLR3 deficiency., Methods: We determined the sequence of all exons of TLR3 in 110 of the 120 patients with HSE enrolled in our study who do not carry any of the previously described HSE-predisposing mutations of TLR3 pathway genes (TLR3, UNC93B1, TRIF, TRAF3, and TBK1). All the new mutant TLR3 alleles detected were characterized experimentally in-depth to establish the causal relationship between the genotype and phenotype., Results: In addition to the 3 previously reported TLR3-deficient patients from the same cohort, 6 other children or young adults with HSE carry 1 of 5 unique or extremely rare (minor allele frequency <0.001) missense TLR3 alleles. Two alleles (M374T, D592N) heterozygous in 3 patients are not deleterious in vitro. The other 3 are deleterious via different mechanisms: G743D+R811I and L360P heterozygous in 2 patients are loss-of-function due to low levels of expression and lack of cleavage, respectively, and R867Q homozygous in 1 patient is hypomorphic. The 3 patients' fibroblasts display impaired TLR3 responses and enhanced herpes simplex virus 1 susceptibility. Overall, TLR3 deficiency is therefore found in 6 (5%) of the 120 patients studied. There is high allelic heterogeneity, with 3 forms of autosomal dominant partial defect by negative dominance or haploinsufficiency, and 2 forms of autosomal recessive defect with complete or partial deficiency. Finally, 4 (66%) of the 6 TLR3-deficient patients had at least 1 late relapse of HSE, whereas relapse occurred in only 12 (10%) of the total cohort of 120 patients., Conclusions: Childhood-onset HSE is due to TLR3 deficiency in a traceable fraction of patients, in particular the ones with HSE recurrence. Mutations in TLR3 and TLR3 pathway genes should be searched and experimentally studied in children with HSE, and patients with proven TLR3 deficiency should be followed carefully., (© 2014 American Academy of Neurology.)

Heterozygous mutations in the NLRP12 gene have been found in patients with systemic auto-inflammatory diseases. However, the NLRP12-associated periodic fever syndromes show a wide clinical spectrum, including patients without classical diagnostic symptoms. Here, we report on a 20-year-old female patient diagnosed with common variable immunodeficiency (CVID), who developed intestinal amyloidosis and carried novel compound heterozygous mutations in NLRP12, identified by whole exome and transcriptome sequencing. CVID is a primary immunodeficiency characterized by low serum immunoglobulins, recurrent bacterial infections and development of malignancy, but it also presents with a magnitude of autoimmune features. Because of the unspecific heterogeneous clinical features of the disease, a delay in diagnosis is common. Secondary, inflammatory (AA type) amyloidosis has infrequently been observed in CVID patients. Based on our case observation and a critical review of the literature, we suggest that NLRP12 mutations might account for a small fraction of CVID patients with severe auto-inflammatory complications., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected., Objectives: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID., Methods: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed., Results: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001)., Conclusions: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications., (Published by Mosby, Inc.)

We report a RAG2-deficient patient with severe combined immunodeficiency and hemophagocytic bone marrow aplasia with plasma cells after a nonconditioned transplantation from a fully matched sibling. After engraftment, disseminated BCGosis appeared because of graft versus host disease prophylaxis. On the 55th day, eosinophilia, neutropenia, and thrombocytopenia developed. Aplasia, hemophagocytic histiocytes, and plasma cells were found on his bone marrow with very high level of serum immunoglobulin E. We could not discriminate exactly whether BCGosis or alloimmune response is the cause of hemophagocytic aplasia with plasma cells. Despite the second hematopoietic stem cell transplantation with a reduced intensity conditioning regime, his marrow aplasia did not recover and he died. This case suggests that BCGosis might be associated with hemophagocytic marrow aplasia with plasma cells in an alloimmune reaction.

Purpose: To report a child with sarcoid choroidopathy that has a similar appearance to birdshot chorioretinopathy., Methods: Observational case report. Review of the clinical examination, laboratory findings, and histopathologic records of a child with sarcoidosis., Results: A 9-year-old girl was examined in a routine consultation demand in our pediatric clinic. Slit-lamp examination revealed granulomatous anterior uveitis, and funduscopic examination of both eyes revealed numerous, oval, irregular, creamy chorioretinal lesions. These were widespread throughout the fundus, except the macula, and had the characteristic funduscopic appearance of birdshot chorioretinopathy. The patient underwent axillary lymph node biopsy that showed noncaseating granulomas consistent with sarcoidosis., Conclusion: Sarcoidosis should be considered in a child with chorioretinal lesions resembling birdshot chorioretinopathy.

SCID is characterized by profound deficiencies of T and B lymphocytes. HSCT is the only curative treatment for children with SCID. The clinical characteristics and outcome of 30 HLA-haploidentical transplantations in 18 patients (15 SCID, two Omenn syndrome, and one MHC Class II deficiency) are reported here. The age of patients at diagnosis ranged from one and half to nine months (median: four months). The median time was one month between the diagnosis and the time of the initial transplantation. Infused CD34+ stem cell dose was ranged between 7 and 94.2 × 10(6) /kg. Nine of 18 patients were found to be positive for CMV antigenemia at diagnosis; therefore, none of them received a conditioning regimen. The most common complication was graft failure (61%), so repeated transplantations (two to four) were performed in seven patients. The mean time of lymphoid engraftment was 17.5 days (median: 16, range: 11-29 days). Ten of 15 SCID (67%) patients survived with a stable complete donor chimerism. However, all three non-SCID patients died. In conclusion, in the absence of a matched family donor, HLA-haploidentical transplantation from parental donors represents a readily available treatment option especially for patients with SCID, offering a high chance of cure., (© 2012 John Wiley & Sons A/S.)

Objective: To evaluate whether the mode of delivery (vaginal versus C-section) influences the levels of CD4+CD25+FOXP3+ Treg cells in cord blood and maternal peripheral blood and also to examine its relationship with plasma cortisol levels., Methods: Newborns either born vaginally (n = 19) or via elective C- section (n = 20) and their mothers, as well as 20 healthy but not pregnant women, were included in the study. CD4+CD25+FOXP3 (Treg) cells were examined by flow cytometry. Total lymphocyte counts (TLC) and serum cortisol levels were also determined for all the groups., Results: The percentages of CD4+CD25+FOXP3 cells and the serum cortisol levels of infants born vaginally (p < 0.004 and p < 0.0001) and their mothers (p < 0.0001 for both) were found to be significantly higher than those of newborns born by C-section and their mothers. Positive correlations were seen between CD4+CD25+FOXP3+ cells (r = 0.741) and serum cortisol levels (r = 0.468). No relationship was observed between newborns delivered by C-section and their mothers (r = 0.022 for both)., Conclusions: This study suggests that mode of delivery affects cord blood Treg cells. Higher CD4+CD25+FOXP3+ Treg cells of newborns and their mothers in vaginal delivery group and their relationship with serum cortisol levels suggest a stress phenomenon related to vaginal delivery.

Purine nucleoside phosphorylase deficiency is a rare immunodeficiency syndrome characterized by recurrent infections, neurological dysfunction, and autoimmunity. Early diagnosis and hematopoietic stem cell transplantation may reverse the dismal prognosis in PNP deficiency. This report presents a new PNP deficiency case successfully transplanted without a conditioning regimen from an HLA-identical family donor, who developed a complication of disseminated BCG infection.

Background: The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial., Methods: Patients with a primary DSM-IV diagnosis of ADHD (N=400; 72 girls, 328 boys, mean age=9.61+/-1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n=202) (150 mg/day) or placebo (n=198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values., Results: Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect., Conclusions: Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels.

Background: Transient tachypnea of the newborn (TTN) is usually a benign self-limiting respiratory disorder in the immediate neonatal period. The lipophilic surfactant-associated protein B (SP-B) was demonstrated to be the most relevant structural component of the surfactant system for immediate postnatal pulmonary adaptation. We hypothesized genetic variations of surfactant protein B (heterozygous 121 ins 2 mutation er intron 4 polymorphisms) to be related to TTN., Patients and Method: We screened genomic DNA of 83 healthy term neonates (gestational age: 39 (37 - 41) completed weeks [median and range]; birth weight: 3325 +/- 541 grams [mean +/- SD]) and 75 infants presenting with TTN (gestational age: 38 (37 - 41) completed wecks [median and range]; birth weight: 3091 +/- 435 grams [mean +/- SD]) by means of PCR-amplification, fragment length and sequence analysis. TTN was diagnosed an the basis of the clinical signs with respiratory rate > 60 breaths/minute, fraction of inspired oxygen > 0.21, and characteristic radiographic findings within less than 24 hours after birth. Newborns with any infection, pulmonary or cardiac congenital malformations, postnatal asphyxia and infants born to diabetic mothers were excluded., Results: In TTN-group the frequency of male infants (68.4 % versus 44.6 %, p < 0.05) and caeserian section were significantly higher (68.4 % versus 30.1 %, p < 0.05). We did not find any statistical difference in frequency of intron 4 variations between controls and TTN-group (8.4 % versus 10.7 %). None of the infants were heterozygous for the 121ins2 SP-B mutation., Conclusions: WC conclude polymorphisms of intron 4 and heterozygous 121 ins 2 mutation not to associated with TTN.

Trichosporon asahii (T. asahii) is an uncommon cause of yeast infection in preterms. We present a 27-week gestational age female with clinical evidence of sepsis, such as patchy infiltrations on chest roentgenogram, and yeast growing in urine and blood cultures. Conventional amphotericin B was empirically added in a dose of 0.5 mg/kg, q8h to standard protocol of the neonatal intensive care unit. Dose of the drug was induced to 1 mg/kg because the patient had not improved when the organism was identified as T. asahii on the pretreatment urine and blood cultures. Both cultures were clear on the 10th day of amphotericin B therapy and treatment was ceased on the 21st day. The patient was healthy when discharged. Trichosporon infections in neonates have been almost uniformly fatal. Most strains of T. asahii may be confused with Candida spp. on initial culture examinations. Therefore, delays in appropriate treatment may occur.

In this paper, we investigated the effects of short-course high-dose methylprednisolone (HDMP) treatment on the proliferation of myeloid lineage cells and on apoptosis of blast cells in eight children with acute lymphoblastic leukemia (ALL). The patients were given the HDMP treatment (30 mg/kg/d, perorally) before 9:00 a.m. for seven days. Bone marrow (BM) aspiration was done at days 0 and 3 of the HDMP treatment in all patients and at the 7th day of the HDMP treatment in six patients. Bone marrow blast cells had gradually decreased after the HDMP treatment by the 7th day. There were statistically significant differences between the mean percentages of BM blast cells at days 0 and 3, days 0 and 7, and at days 3 and 7 (p<0.05). The mean percentages of blast cell apoptosis at the 3rd day was significantly higher than at days 0 and 7, and apoptosis at day 0 was significantly lower than at the 7th day (p<0.05). The mean percentages of BM myeloid lineage cells at the 7th day was significantly higher than at days 0 and 3 (p<0.05), and the mean percentage at day 0 was significantly lower than at the 3rd day (p<0.05). These findings indicate that short-course HDMP treatment causes apoptosis on lymphoblasts and increases the proliferation of myeloid lineage cells in children with ALL.

A randomized, double-blinded, placebo-controlled trial was conducted of early administration of recombinant granulocyte colony-stimulating factor (rGCSF) to 40 non-neutropenic, preterm infants between 33 and 36 weeks of gestational age with the diagnosis of presumed sepsis. The treatment group (n = 20) received 5 microg/kg per day of intravenous rGCSF once daily for 3 d and the control group (n = 20) received the same volume of physiological serum. Immediately before the first dose and on the 4th day, plasma levels of GCSF and tumour necrosis factor-alpha (TNF-alpha), absolute neutrophil counts (ANC), immature neutrophil count (INC), immature/total neutrophil (I/T) ratios and platelet counts were determined. At study entry, the plasma GCSF and TNF-alpha levels were similar. On day 4, there was no significant change in GCSF levels in either groups, whereas there was a significant decrease in TNF-alpha levels in the treatment group. ANC and INC of the treatment group also increased significantly. The I/T ratio continued at the same level in the treatment group, but decreased significantly on days 4 and 7 day in the control group. The length of time on the neonatal intensive care unit (NICU) was significantly shorter in the treatment group. In conclusion, early administration of 3 daily doses of rGCSF (5 microg/kg per day) to non-neutropenic, preterm infants who had presumed sepsis increased circulating ANC and INC, decreased plasma TNF-alpha levels and shortened the length of time on the NICU.

Background: The purpose of the present study was to evaluate the severity of and factors related to osteopenia in children with cerebral palsy (CP)., Methods: Bone mineral density (BMD), calcium (Ca), phosphate (P), alkaline phosphatase (ALP), creatinine, parathyroid hormone (PTH) and 25-hydroxy vitamin D3 (25OHD3) concentrations were determined in 24 children with CP (15 ambulant, nine non-ambulant), aged between 10 months and 12 years (mean (+/-SD) 4.1+/-2.9 years). These vaules were compared with data obtained from a control group., Results: Adjusted mean BMD values were lower in the patient group than in controls (P<0.05). However, there was no difference between BMD values of ambulant and non-ambulant patients. The Ca and P levels of the patient group were significantly higher than those of controls (P<0.05)., Conclusions: The present study showed that BMD was decreased in all children with CP, but to a greater extent in non-ambulant children with CP, and immobilization is the major effective factor on bone mineralization.

Abscess formation by Salmonella species is an uncommon but significant manifestation of salmonellosis, because this type of infection has high morbidity and mortality rates and is a potential nosocomial hazard. In infants, history of consumption of contaminated water should be especially quired. We report a case who had sepsis and multiple brain abscesses due to Salmonella paratyphi B and who responded to sulbactam-ampicillin (SAM) therapy. Sulbactam-ampicillin combination may be preferable due to its immunomodulator effect.

Focal calcification is an occasional tubular abnormality seen in minimal-change nephrotic syndrome. Nephrocalcinosis was also reported in premature infants as a consequence of hypercalciuria resulting from long-term furosemide therapy. We describe 4 nephrotic children (3 minimal change, 1 diffuse proliferative glomerulonephritis) with transient hypercalciuria and intraluminal calcifications in renal histopathological specimens without radiologic evidence of renal calcification. These children were resistant to corticosteroid therapy and were receiving furosemide therapy along with albumin for management of oedema. Two of the children also had urinary infection. We were concerned that children with nephrotic syndrome are at risk for nephrocalcinosis, and urinary calcium and pH should be monitored carefully during prolonged furosemide use, especially in children with nephrotic syndrome with reduced initial responsiveness to corticosteroid therapy. HUM PATHOL 31:1363:1367., (Copyright 2000 by W.B. Saunders Company)

Fanconi's anemia (FA) is an autosomal recessive disease manifested by pancytopenia resulting from bone marrow failure, variable physical anomalies and cancer susceptibility. A seven-year-old girl with Fanconi's anemia-like congenital aplastic anemia and concurrent asplenia without the congenital heart defects or the abdominal heterotaxia is reported. Asplenia was indicated using denatured red cells labelled with 51Cr, abdominal ultrasonography and computerized tomography. Immunological studies showed immunoglobulins (IgG, IgA, IgM), C3 and C4 levels within normal limits and the percentage of CD3, and C4 cells and the CD4/CD8 ratio decreased. The patient had not been exposed to recurrent pneumococcal infections. We think that isolated asplenia may occur in patients with Fanconi's anemia-like congenital aplastic anemia without the congenital heart diseases or abdominal heterotaxia.

Infection-associated hemophagocytic syndrome (IAHS) is a form of the reactive hemophagocytic syndrome. IAHS is associated with viral, bacterial, fungal, mycobacterial, rickettsial and protozoal infections and with various malignant neoplasms. A more accurate designation for this acquired form of the syndrome is reactive hemophagocytic syndrome (HS). Reactive HS is characterized by malaise, fever, hepatosplenomegaly, lymphadenopathy, cytopenia, hypertriglyceridemia, hypofibrinogenemia and hemophagocytosis. Cyclosporin A, VP-16, high-dose steroids, and intravenous immunoglobulin (IVIG) have been used in the treatment of IAHS. Here, a 10-year-old girl with reactive HS due to possible viral infection was treated successfully with cyclosporin A and IVIG. Fever disappeared on the third day, complete blood count reached normal levels on the sixth day and hepatosplenomegaly disappeared on the ninth day after treatment. We believe cyclosporin A and IVIG may be used in the treatment of reactive HS, at least in selected patients. Further studies are required to confirm its role as first-line therapy for children with IAHS.

To evaluate the prognosis of breath holding spells (BHS) after iron treatment, 91 children (56 boys, 35 girls) aged between 6 months and 40 months (median, 17) were followed prospectively for a median of 45 months (range, 6-89). In 49 of the children, the frequency of BHS was less than 10 each month, in 22 it was 10-30 each month, and in 20 more than 30 each month. The spells were cyanotic in 60 children. All patients were evaluated initially and during follow up for haematological indices. Electroencephalographic and electrocardiographic abnormalities were also recorded. Sixty three patients were found to have iron deficiency anaemia and were treated with iron (6 mg/kg/day) for three months. Other patients were not given any treatment. After three months, there was a significant difference for correction of cyanotic spells between children who had been treated with iron and those who had not (84.1% v 21.4%). During further follow up, febrile convulsions occurred in 10 children (six were on iron treatment initially). It appears that treating iron deficiency anaemia is effective in reducing the frequency of BHS.

In this study the apoptotic effects of heparin on lymphoblasts, neutrophils, and mononuclear cells were evaluated by flow cytometry for detection of sub-G1 peak, in vitro. Ten children with acute lymphoblastic leukemia (ALL) at diagnosis (Group I), six children with ALL at relapse (Group II), and 10 healthy children (controls) were included in this study. Lymphoblasts in ALL patients, and neutrophils and mononuclear cells in controls, were incubated in increasing heparin concentrations (0, 5, 10, 20 U/ml). Flow cytometric analyses were performed at 0, 1, and 2 hours of incubation in heparin for determination of the apoptotic effects of heparin. In Group I apoptosis was detected in all different levels of heparin concentration except 0 U/ml at 0, 1, and 2 hours. The apoptotic effects of heparin on blast cells peaked at the first hour in 5-, 10-, and 20-U/ml heparin concentrations (p < 0.0001). In Group II similar findings were observed only at zero hour and apoptosis was higher than those in Group I except in 5-U/ml heparin concentration (p < 0.001). Apoptosis was found to increase with heparin levels in both groups (p < 0.02). In the control group, apoptosis was detected only at the 20-U/ml heparin concentration and only at the first and second hours. Lymphoblasts are more sensitive to apoptotic effects of heparin than either neutrophils and mononuclear cells (p < 0.004). It can be suggested that low-dose heparin may cause significant apoptosis of lymphoblasts while inducing no apoptosis on neutrophils and mononuclear cells. The findings of this preliminary study indicate that further and more comprehensive research on the apoptotic effect of heparin on lymphoblasts should be done.

Fungal brain abscess is rarely cured in childhood. The mortality rate is higher than 95% in immunocompromised patients, even if antifungal agent and surgery are used. A 5-year-old boy with acute myeloblastic leukemia (AML) (M2 according to FAB classification) and multiple candidal brain abscesses is discussed. The candidal brain abscesses of this patient were thought to be iatrogenic, due to the difficult lumbar puncture of intratechal therapy. He was successfully treated with combination conventional amphotericin B (ABC), surgical drainage, and granulocyte colony-stimulating factor. Toxicity was not determined due to ABC. This is thought to be the first child to survive AML and multiple candidal brain abscesses.

Multiple vertebral segmentation defects i.e. multiple malformations of vertebrae and ribs are characterized by short neck, scoliosis, short trunk and deformity of the ribcage. There are three major subtypes; Jarcho-Levin syndrome, spondylothoracic dysostosis and spondylocostal dysostosis, with different inheritance patterns, survival rates and associated malformations. We describe three cases of multiple vertebral segmentation defects, two with familial spondylothoracic dysostosis and one with sporadic spondylothoracic dysostosis, and anomalies i.e. super-numerary breast, clubfeet deformity, myelomeningocele, intradural lipoma, and Arnold-Chiari malformation.

The Chédiak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency disorder. Some cases with CHS develop the accelerated phase characterized by pancytopenia, high fever and lymphohistiocytic infiltration of liver, spleen and lymph nodes. The treatment of the accelerated phase of CHS is difficult. We describe a case with CHS in the accelerated phase who had multiple polyposis and pulmonary infiltration that was probably due to involvement of CHS. She was successfully treated with high-dose methylprednisolone at her first admission. At her second admission, splenectomy was performed to remove hypersplenism, and her clinical, radiological and hematological findings improved significantly.