The role of active B cells in allergen immunotherapy

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 (AU)

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The role of active B cells in allergen immunotherapy.

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.

A comparison of B cell subsets in primary immune deficiencies that progress with antibody deficiency and age-matched healthy children

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

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A comparison of B cell subsets in primary immune deficiencies that progress with antibody deficiency and age-matched healthy children.

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.

Is parturition-timing machinery related to the number of inhibitor CD94/NKG2A positive uterine natural killer cells?

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.

Comparison of major lymphocyte subpopulations and recent thymic emigrants in patients with ataxia telangiectasia and age-matched healthy groups.

BACKGROUND: Ataxia telangiectasia (A-T) is a genetic disorder caused by the homozygous mutation of the A-T mutated gene. It is frequently associated with variable degrees of cellular and humoral immunodeficiency. However, the immune defects in A-T patients are not well characterized. To the best of our knowledge, no studies have focused on the major lymphocyte subpopulations and recent thymic emigrants of A-T patients in comparison with age-matched healthy controls. METHODS: Following the European Society for Immunodeficiencies criteria, 17 patients diagnosed with A-The, and 12 age-matched healthy children were assigned to the study. Both patients and healthy controls were grouped as 1-5, 6-10, 11-15, and 15+ years. By using a flow cytometer, major lymphocyte subpopulations and CD4+CD45RA+CD31+ recent thymic emigrants were determined as percentage and absolute cell numbers and compared. RESULTS: No significant differences in all lymphocyte subpopulations were observed between the age groups of A-T patients. Compared to the healthy controls, there was a decrease in T cells, effector memory T4 cells, B cells, naïve B cells, naïve T4 cells, switched B cells, and recent thymic emigrants and an increase in active T8 cells and non-switched B cells in the percentage and absolute number of some cell populations in the A-T group. CONCLUSIONS: This study showed that effector functions in some cell lymphocyte populations were decreased in A-T patients.

Transient tachypnea of the newborn (TTN): a role for polymorphisms of surfactant protein B (SP-B) encoding gene?

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.

Sepsis and multiple brain abscesses caused by Salmonella paratyphi B in an infant: successful treatment with sulbactam-ampicillin and surgical drainage.

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.

Bone mineral density in children with cerebral palsy.

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.

Microscopic nephrocalcinosis and hypercalciuria in nephrotic syndrome.

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.

Asplenia in a patient with Fanconi's anemia-like congenital aplastic anemia.

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.

Successful treatment of reactive hemophagocytic syndrome with cyclosporin A and intravenous immunoglobulin.

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.

Breath holding spells in 91 children and response to treatment with iron.

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.

Apoptotic effects of heparin on lymphoblasts, neutrophils, and mononuclear cells: results of a preliminary in vitro study.

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.

Multiple fungal brain abscess in a child with acute myeloblastic leukemia.

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. Brief report of three patients and nosological considerations.

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 role of high dose methylprednisolone and splenectomy in the accelerated phase of Chédiak-Higashi syndrome.

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.