Noriaki Shinomiya

Serum levels of Th2 chemokines, CCL17, CCL22, and CCL27, were the important markers of severity in infantile atopic dermatitis

Atopic dermatitis (AD) is considered to be Th2 cell‐mediated disorder. In most infants with AD, AD may be induced by food allergy. In the early stage of infantile AD, it is unclear whether there are changes in serum Th2 chemokines or in Th2 chemokine production by peripheral blood mononuclear cells (PBMC). Thirty‐four patients with AD were examined (mean age, 4.5 months; female:male, 18:16). Ten age‐matched infants with no history of allergic disease were used as controls. Thirty of these 34 patients were sensitized with ovalbumin (OVA; radioallergrosolvent score of >2). Serum levels of CCL17, CCL22, and CCL27 were measured with enzyme‐linked immunosolvent assay (ELISA) kits and their correlation with the severity of skin lesions, defined by the scoring atopic dermatitis (SCORAD) index, was analyzed. The amounts of TNF‐α, CCL17, CCL22, and CCL27 in the culture supernatants of PBMC from OVA‐sensitized AD infants after stimulation with OVA were estimated with ELISA kits. Elevated serum CCL17, CCL22, and CCL27 levels significantly correlated with SCORAD index (r = 0.7181, p < 0.001; r = 0.5354, p < 0.005; r = 0.8312, p < 0.0001, respectively). CCL22 levels produced by PBMC from OVA‐sensitized infants with AD reflected serum CCL22 levels. Only six of 30 OVA‐sensitized patients in whom the skin signs increased immediately after OVA intake showed markedly high titers of TNF‐α produced by PBMC after stimulation with OVA. These high TNF‐α titers correlated significantly with serum CCL27 levels (r = 0.7181, p < 0.001). Serum concentrations of CCL17, CCL22, and CCL27 correlate well with the extent and intensity of AD in infants. Of the three Th2 chemokines examined, serum CCL27 correlated most significantly with the severity of AD. Thus, the peripheral immune responses of infantile AD patients are skewed to a Th2 dominant bias.

Mouthpiece versus facemask for delivery of nebulized salbutamol in exacerbated childhood asthma.

We compared the bronchodilator response to salbutamol (albuterol) delivered by a compressed air nebulizer through a mouthpiece and via a facemask in 18 asthmatic children, to determine the most appropriate delivery method. Patients using a mouthpiece had significantly better mean percent increases in forced expiratory volume in 1 sec (FEV1) and in forced vital capacity (FVC) than those using a facemask 30 min after inhalation (FEV1: 56.4 ± 32.6 % vs. 28.9 ± 19.1%, FVC: 34.4 ± 26.4% vs. 7.5 ± 14.9%, respectively). Nebulized therapy plays an important role in the management of bronchial asthma in children and should be delivered by a mouthpiece whenever possible in cases of exacerbated asthma.

Acute myeloblastic leukemia associated with trisomy 8 and translocation 8;21 in a child with Down syndrome

The present study examined an 11-year-old girl with Down syndrome who suffered from acute myeloblastic leukemia (AML) preceded by preleukemic pancytopenia. Chromosomal analysis of leukemic cells revealed a chromosome change at t(8;21) and trisomy 8 associated with constitutional trisomy 21. Treatment with antineoplastic agents led to complete remission.

A study of the factors inducing the development of childhood-onset myasthenia gravis using CDR3 spectratyping analysis of the TCR repertoire

Myasthenia gravis (MG) is an autoimmune disease. AChR-specific autologous helper T (Th) cells are essential to the pathogenesis of MG. Factors correlated with the development of childhood-onset MG are unknown. In longitudinal studies, we found TCR Vbeta 2/5.1/6/7 usage in the development or relapse phases, but not in the remission phase. We also found that TCR Vbeta 8/9/13.1/15/18/20 usage persisted. The polyclonally expanded TCR Vbeta 2/5.1/6/7 by CDR3 spectratyping was found to be associated with the development of disease. These data suggest that in patients with childhood-onset MG, stimuli such as superantigens induced by a preceding infection, which cause development of the polyclonal pattern in TCR Vbeta families, play an important role in the development of the disease.

Common acute lymphoblastic leukemia preceded by hypercalcemia in an infant.

A case of common acute lymphoblastic leukemia (ALL) preceded by hypercalcemia was observed in an infant. A high blood level of parathyroid hormone related protein (PTH‐rP) was detected during the first examination at Ohashi Hospital. Treatment with antineoplastic agents led to complete remission. The blood PTH‐rP level decreased as a result of treatment. PTH‐rP produced by leukemic cells was thought to be the cause of the hypercalcemia.

Maternal germinal mosaicism of X-linked agammaglobulinemia

X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by abnormalities in tyrosine kinase (BTK), and is characterized by a deficiency of peripheral blood B cells. We studied cytoplasmic expression of BTK protein and analyzed the BTK gene (BTK) in peripheral blood mononuclear cells from two siblings with XLA and additional family members. Cytoplasmic expression of BTK protein in monocytes was not detected in either patient with XLA. A single base deletion (C563) in BTK-exon 6, which encodes the TH domain, was identified in both XLA patients. However, normal cytoplasmic expression of BTK protein in monocytes was detected in their mother without any BTK mutation. These results strongly suggest germinal mosaicism in the mother.

Incomplete Sjögren-Larsson Syndrome in Two Japanese Siblings

Sjögren-Larsson syndrome (SLS) is a rare, autosomal recessive disorder characterized by ichthyosis, spastic diplegia and mental retardation. Biochemical studies have pinpointed the pathogenesis resulting in the deficiency of the fatty aldehyde dehydrogenase (FALDH) component of the fatty alcohol NAD+ oxidoreductase complex. Histochemical analysis revealed a reduction in alcohol dehydrogenase (AD) activity in the skin. SLS patients have been categorized biochemically into two groups: complete and incomplete reduction according to the degree of FALDH deficiency. Our patients demonstrated incomplete clinical features, including a 1/3 reduction in FALDH activity, and decreased AD activity in the ichthyotic lesion. The phenotypical differences between our cases and classic SLS are probably due to the partial FALDH deficiency.

Point mutation in intron 11 of Bruton's tyrosine kinase in atypical X-linked agammaglobulinemia

had been based on fundamental criteria, such as family history, recurrent bacterial infections in late infancy and very low levels of serum immunoglobulins of all isotypes. Typical XLA patients generally demonstrate a deficit in peripheral B cells, but patients with atypical XLA may have substantial levels of immunoglobulin and peripheral B cells with variable clinical findings.1,2 Genetic diagnosis of XLA has become possible3 due to the discovery of the Bruton tyrosine kinase (Btk) gene, composed of an src homology 1 (SH1) domain (kinase domain), an SH2 and an SH3 domain, as the etiological gene. We report herein on a pediatric patient with XLA who had no recurrent bacterial infections and no family history of XLA. The XLA was diagnosed only from studies of Btk protein expression and Btk genomic DNA.

A variant of childhood-onset myasthenia gravis: On HLA typing and clinical characteristics in Japan

To investigate the correlation between clinical features and HLA DR/DQ genetic variability in myasthenia gravis (MG), we evaluated HLA DR/DQ allele frequencies in 87 Japanese patients with childhood-onset disease. HLA genotypes DRB1*1302/DQA1*0102/DQB1*0604 and DRB1*0901/DQA1*0301/DQB1*0303 were significantly higher in patients than in healthy controls (P(c) < 0.0001, RR = 5.5; P(c) < 0.0001, RR = 8.5, for two genotypes, respectively). Patients who had a significantly higher likelihood of the HLA types DRB1*1302/DQA1*0102/DQB1*0604 or DRB1*0901/DQA1*0301/DQB1*0303 belonged to the latent general type (LG) of MG; this is clinically ocular type, but shows myasthenic electromyographic findings in extremity muscles. The LG type of MG was observed in 78% of patients exhibiting the clinically ocular type; this group comprised approximately 75% of patients with childhood-onset MG. These date suggest that LG type of MG may present a particular subset of childhood-onset MG, which is associated with the specific HLA subtypes DRB1*1302/DQA1*0102/DQB1*0604 and DRB1*0901/DQA1*0301/DQB1*0303.

Effect of the Vascular Endothelial Growth Factor (VEGF) on Liver Dysfunction in the Acute Phase of Kawasaki Disease

Kawasaki disease (KD) is an acute type of systemic vasculitis characterized by a remarkable activation of the inflammatory response. Most KD patieents were complicated with the liver dysfunction in the acute phase. To investigate the pathogenesis of the l iver dysfunction, we measured the serum levels of inflammatory cytokines including interleukin (IL)-6, interferon-γ, tumor necrosis factor-α, transforming growth factor-β, IL-10, or vascular endothelial growth factor (VEGF), which were re lated with the pathogenesis of the vasculitis, and the serum levels of albumin and C-reactive protein (CRP) as the indicator of the acute inflammatory response in 35 KD patients. The nineteen of 35 KD patients (54.3%) suffered liver dysfunction (AST50 IU). Neither albumin nor CRP were significantly elevated in the serum of patients with liver dysfunction compared with those without liver dysfunction. Of the measured cytokines, only VEGF was significantly elevated in the patients with liver dysfuncti on compared with patients without liver dysfunction (p<0.05). We presume that this high level of serum VEGF was caused with the thrombocytosis of KD disease. These results suggest that the liver dysfunction in the acute phase of KD was induced via end o thelial cells activated by VEGF.