Kazushige Nagai

Lactoferrin and surfactant protein A exhibit distinct binding specificity to F protein and differently modulate respiratory syncytial virus infection.

Surfactant protein A (SP‐A) and lactoferrin (LF) play important roles in innate immune systems in the respiratory mucous membranes. We investigated how SP‐A and LF act against respiratory syncytial virus (RSV) infection. The present study indicated that RSV‐induced IL‐8 secretion from HEp‐2 cells was up‐regulated by SP‐A (170% of control) but down‐regulated by LF (23% of control). RSV infectivity determined by viral titers and the uptake of FITC‐labeled RSV were also increased by SP‐A, but decreased by LF. To clarify the mechanism of these opposite effects, we examined the interactions of SP‐A and LF with RSV F protein, the most important surface glycoprotein for viral penetration. RSV F protein was found to be the ligand for both SP‐A and LF, but the manners of binding were different. LF directly interacted with the F1 subunit, which involved antigenic sites of F protein. Contrarily, SP‐A associated with the F2 subunit, which was highly glycosylated. SP‐A but not LF failed to interact with deglycosylated F protein. Moreover, SP‐A initiated the hemolyzing fusion activity of F protein. These results suggest that SP‐A and LF modulate RSV infection by different binding specificity to F protein.

Comparison of an Immunochromatography Test with Multiplex Reverse Transcription-PCR for Rapid Diagnosis of Respiratory Syncytial Virus Infections

ABSTRACT A new commercial rapid 10-min one-step immunochromatography (IC) test, SAS RSV test, was compared to another IC test, Directigen EZ RSV, employing RT-PCR as the “gold standard” for detecting respiratory syncytial virus. Of 102 clinical samples, 79 were positive by RT-PCR, 66 (82.5%) were positive with the SAS RSV test, and 55 (69.6%) were positive with Directigen EZ RSV. The specificity of the new test was 91.3% (21 of 23), similar to that of Directigen EZ RSV (100% [23 of 23]). This test performs well enough to be used for patient care.

Clinical and laboratory features of fatal rapidly progressive interstitial lung disease associated with juvenile dermatomyositis

OBJECTIVE Rapidly progressive interstitial lung disease (RP-ILD) is a rare but potentially fatal complication of JDM. The aim of this study was to establish markers for the prediction and early diagnosis of RP-ILD associated with JDM. METHODS The clinical records of 54 patients with JDM were retrospectively reviewed: 10 had RP-ILD (7 died, 3 survived), 19 had chronic ILD and 24 were without ILD. Routine tests included a high-resolution CT (HRCT) scan of the chest and measurement of serum levels of creatine phosphokinase, ferritin and Krebs von den Lungen-6 (KL-6). Anti-melanoma differentiation-associated gene 5 (MDA5) antibodies and IL-18 levels were measured by ELISA. RESULTS No differences were found in the ratio of juvenile clinically amyopathic DM between the three groups. Initial chest HRCT scan findings were variable and could not distinguish between RP-ILD and chronic ILD. Anti-MDA5 antibodies were positive in all 8 patients with RP-ILD and 10 of 14 with chronic ILD, but none of the patients without ILD. Serum levels of anti-MDA5 antibody, ferritin, KL-6 and IL-18 were significantly higher in the RP-ILD group than in the chronic ILD and non-ILD groups. Serum levels of IL-18 positively correlated with serum KL-6 (R = 0.66, P < 0.001). CONCLUSION High serum levels of IL-18, KL-6, ferritin and anti-MDA5 antibodies (e.g. >200 units by ELISA) are associated with RP-ILD. These can be used as an indication for early intensive treatment. Both alveolar macrophages and autoimmunity to MDA5 are possibly involved in the development of RP-ILD associated with JDM.

Effect of maternal antibody on IgA antibody response in nasopharyngeal secretion in infants and children during primary respiratory syncytial virus infection

The IgA antibody response to respiratory syncytial virus (RSV) was determined in nasopharyngeal secretions (NPS) of 22 infants and children infected with RSV group A strains, employing an ELISA. The antibody activity observed during the convalescent phase against whole virus, fusion glycoprotein (F) and large glycoprotein (G) was examined in young infants (under 6 months) and compared with that of older individuals (6 to 16 months). Both groups showed similar degrees of IgA antibody activity to whole virus in NPS; however, older individuals showed a significantly higher activity of IgA F antibody than that of IgA G antibody in the NPS. On the other hand, in the NPS of young infants, IgA F antibody was somewhat suppressed and IgA G antibody activity predominated over that of IgA F. Pre-existing (maternal) serum IgG anti-RSV F antibody activity was higher than that of antibody to G. A significant reverse correlation was observed between the activity of pre-existing serum IgG F antibody and NPS IgA F antibody in the convalescent phase after primary infection with RSV. These observations suggest that maternally derived RSV IgG antibody, which contains abundant anti-F activity, may suppress the development of IgA F antibody response at infection sites in the respiratory tract in young infants during primary RSV infection. These changes may be related to the severity of acute infection and longer convalescence often observed in young infants during RSV infection.

Clinical Characteristics of Respiratory Syncytial Virus (RSV) Subgroup Infections in Japan

The subgroup characteristics of 130 strains of respiratory syncytial virus (RSV) isolated in Sapporo during 9 epidemic years 1980-1989 were determined. Monoclonal antibodies raised against the RSV Long strains were used. Subgroup A included 77 (59.2%) isolates and subgroup B 52 (40.0%) strains, while 1 strain was considered to be a variant of a subgroup A strain. The distribution by age of infants and children was different for the 2 subgroups: less than 1 year of age infants with subgroup A infection dominated, greater than 1 year of age subgroup A infections were less common than subgroup B infections. These was no difference in type of illness between the subgroups. Bronchiolitis was the dominant diagnosis in all patients.

Anti-CADM-140 Antibody-positive Juvenile Dermatomyositis with Rapidly Progressive Interstitial Lung Disease and Cardiac Involvement

To the Editor: Extramusculocutaneous manifestations in juvenile dermatomyositis (JDM) may lead to life-threatening consequences. Interstitial lung disease (ILD) has been reported as one such serious complication in JDM1,2,3,4; how ever, cardiac involvement in JDM is a rare complication and is seldom reported5,6. Recently, anti-CADM-140 autoantibody was discovered in amyopathic dermatomyositis and was associated with rapidly progressive ILD7,8. We describe a fatal case of JDM complicated by ILD and cardiac involvement in which serum preserved at admission was shown to contain anti-CADM-140 antibody. A 9-year-old boy was admitted to our hospital with a 4-month history of low-grade fever and erythematous rashes on his face, hands, elbows, and knees. He was developmentally delayed from an unknown cause. He could not describe muscle weakness or tenderness but showed claudication indicating lower-limb muscle weakness. He had Gottron’s papules but no heliotrope rash. Cardiac sounds revealed a gallop rhythm and he had fine crackles over both lung fields. His erythrocyte sedimentation rate was 38 mm/h, white cell count 1800/μl, … Address correspondence to Dr. Nagai; E-mail: nkazu{at}sapmed.ac.jp

Genetic Variability and Molecular Epidemiology of Respiratory Syncytial Virus Subgroup A Strains in Japan Determined by Heteroduplex Mobility Assay

ABSTRACT We used heteroduplex mobility assay (HMA) to determine the genetic variability of 118 respiratory syncytial virus (RSV) field isolates from 19 epidemics occurring in a Japanese urban area between 1980 and 2000. Nucleotides 1 to 584 of the attachment G glycoprotein gene were amplified by reverse transcription-PCR, and the PCR amplicons were analyzed by HMA by using the earliest isolate from 1980 as the reference throughout. We also performed PCR-restriction fragment length polymorphism (RFLP) analysis and phylogenetic analysis on the same nucleotide sequence. PCR-RFLP revealed 9 patterns, whereas HMA produced 31 distinct patterns. The RFLP patterns were divided into two to seven distinct HMA genotypes. Field strains with similar degrees of G gene nucleotide differences from the reference strain often showed distinct HMA types. The RSV genetic heterogeneity detected by direct sequencing of the PCR amplicon was usually identical to HMA analysis. Analysis of the molecular epidemiology of RSV subgroup A isolates obtained by HMA showed that new RSV variants emerged with each epidemic and that previously dominant variants seldom recurred in subsequent epidemics. HMA is useful in detecting genetic variants of RSV subgroup A and has some advantages over other conventional methods.

A case report of cutaneous polyarteritis nodosa in siblings

Abstract Cutaneous polyarteritis nodosa (CPAN) is characterized by a necrotizing vasculitis of small and medium-sized arteries in the skin, which can be associated with fever, arthralgia, myalgia, and neuropathy, but, unlike polyarteritis nodosa (PAN), there is no visceral involvement. CPAN is rare in childhood. We report two siblings who developed CPAN during childhood. Interestingly, both had Mediterranean fever gene (MEFV) mutation, i.e. heterozygous E148Q. They also shared HLA-A24, -DR15 alleles. Simultaneous occurrence of MEFV mutation and HLA alleles with CPAN has never been reported in Japan. These cases could provide some hereditary clue for the development of CPAN.

Characteristics and outcome of intractable vasculitis syndrome in children: Nation-wide survey in Japan

Abstract Objective: Primary systemic vasculitis (PSV) is a rare disorder in children and difficult to distinguish from other diseases. However, appropriate diagnosis and prompt treatment will affect on the morbidity and mortality of intractable PSV. In this study, we conducted a nationwide survey in Japan, to clarify epidemiology and clinical outcome of PSV. Methods: We had sent survey questionnaires to most of the Japanese institutions that employed pediatricians, requesting the number of patients with refractory PSV who were diagnosed and treated between 2007 and 2011. Respondents were asked to provide detailed information on the clinical and laboratory features of each case they had managed. Those with Kawasaki disease or Henoch–Shönlein purpura vasculitis (IgA vasculitis) were excluded. Results: Of all the institutions surveyed, 1123 (37.3%) patients responded, finally, total of 49 patients with intractable PSV, defined by those with resistant to treatment and steroid-dependent, or with any complication associated with prognosis, were selected. The diagnosis was Takayasu arteritis in 31, polyarteritis nodosa in 11, granulomatosis with polyangitis in 2, microscopic polyangitis in 1, and ANCA negative microscopic polyangitis in 1. In those with Takayasu arteritis, 67% were treated with an immunosuppressive agent, 22% with biological modifiers, and 16% with surgical procedures. In other types of disease, 88% of the patients were treated with an immunosuppressive agent, and 12% with biological modifiers. Two with Takayasu arteritis died being terminally ill. Conclusion: This nationwide survey establishes the heterogeneous characteristics of PSV in children. Although questionnaire-based, the results of our analysis should be useful in planning prospective studies to identify the most effective therapy for each subtype of multifaceted disease.

Importance of Information Sharing to Improve Immunization Coverage for the Expanded Programme on Immunization in Lao People's Democratic Republic

This letter explains the results of a survey in Lao Peoples Democratic Republic (PDR) to determine how mothers perceived immunization and their attitudes towards vaccinating their children. It shares that the results prompted two important strategies to improve vaccination coverage in Lao PDR--first the regular circulation of proper and practical information on immunization to communities and second the sharing of information on immunization with mothers in a community.