Defective killer cell activity in patients with chronic active Epstein-Barr virus infection.

Natural killer (NK) cell activity, lymphokine activated killer (LAK) activity and Epstein-Barr virus specific cytotoxic T lymphocyte (EBV-CTL) activity were examined in 10 children with chronic active EB-virus infection and an adult with persistently positive early antigen-antibody to EB-virus. NK cell activity against erythroleukemia cell line K-562 was significantly (p less than 0.005) lower in the patients (22.3 +/- 8.5%, mean +/- SD) than in normal controls (40.4 +/- 15.9%). Spontaneous cytotoxicity against an EB-virus transformed autologous lymphoblastoid cell line was 15.0 +/- 7.6% in the patients, and was comparable to spontaneous cytotoxicity activity in normal controls (11.7 +/- 4.3%). LAK activity against Raji cells was significantly (p less than 0.02) lower in the patients (14.6 +/- 11.4%) than in normal controls (29.2 +/- 15.9%). EBV-CTL activity against an EB-virus transformed autologous lymphoblastoid cell line was significantly (p less than 0.005) lower in the patients (11.8 +/- 5.5%) than in seropositive normal controls (33.7 +/- 14.7%). No regression of the lymphoblastoid cell line was observed when EBV-CTL activity of the patients was tested by regression assay. It is conceivable that defects in both EB-virus specific and nonspecific killer cell activities play important roles in the pathogenetic abnormalities which allow EB-virus infection to progress to a chronic active state.</p

Elevated IgA antibodies to Epstein-Barr virus in children with chronic active Epstein-Barr virus infection.

Anti-Epstein-Barr virus (EBV) antibodies were tested in 11 children with chronic active EBV infection. Anti-virus capsid antigen (VCA)-IgG antibody titers ranged from 1:640 to 1:10,240. Anti-VCA-IgM antibody was consistently positive in 5 of the 11 patients; anti-VCA-IgA antibody was consistently positive in 6 of the 10 patients; anti-early antigen (EA)-IgG antibody was consistently positive in 10 of the 11 patients and anti-EA-IgA antibody was consistently positive in 4 out of the 7 patients. Anti-EBV nuclear antigen (EBNA) antibody was not detected in two patients. Consistently positive anti-VCA-IgA- and anti-EA-IgA- antibody may be a characteristic feature of abnormal antibody responses in severe chronic active EBV-infection in childhood.</p

Hyperreactivity of lymphocytes to streptolysin O and lack of plasma inhibitory factor (s) in patients with mucocutaneous lymphnode syndrome.

Lymphocyte activation by streptolysin O (SLO) and factors in the plasma which inhibit the response to SLO were examined in 19 patients with mucocutaneous lymphnode syndrome (MCLS), 54 age-matched (6 months-6 years) normal children, 41 normal children older than 6 years and 10 normal adults. In normal children younger than 6 years, the response to SLO was weak and in many cases no response was seen. On the other hand, in the patients with MCLS, the response of lymphocytes to SLO was high and comparable to the response in adults and children older than 6 years. The DNA synthesis of lymphocytes stimulated by SLO was inhibited almost completely by autologous or allogeneic plasma of many of the normal children and adults. The plasma of patients with MCLS did not inhibit, but rather enhanced the response to SLO. These results suggest that the increased response of lymphocytes to SLO and the lack of plasma inhibitory factors in patients with MCLS may be due to the immune response to the pathogen of MCLS, as yet undiscovered.</p

Interferon-α/β receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006

BACKGROUND: Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are known to exert a strong adjuvant effect on Th1 immune responses. Although several genes have been reported, no comprehensive study of the gene expression profiles in human cells after stimulation with CpG ODN has been reported. RESULTS: This study was designed to identify a CpG-inducible gene cluster that potentially predicts for the molecular mechanisms of clinical efficacy of CpG ODN, by determining mRNA expression in human PBMC after stimulation with CpG ODN. PBMCs were obtained from the peripheral blood of healthy volunteers and cultured in the presence or absence of CpG ODN 2006 for up to 24 hours. The mRNA expression profile was evaluated using a high-density oligonucleotide probe array, GeneChip(®). Using hierarchical clustering-analysis, out of a total of 10,000 genes we identified a cluster containing 77 genes as having been up-regulated by CpG ODN. This cluster was further divided into two sub-clusters by means of time-kinetics. (1) Inflammatory cytokines such as IL-6 and GM-CSF were up-regulated predominantly 3 to 6 hours after stimulation with CpG ODN, presumably through activation of a transcription factor, NF-κB. (2) Interferon (IFN)-inducible anti-viral proteins, including IFIT1, OAS1 and Mx1, and Th1 chemoattractant IP-10, were up-regulated predominantly 6 to 24 hours after stimulation. Blocking with mAb against IFN-α/β receptor strongly inhibited the induction of these IFN-inducible genes by CpG ODN. CONCLUSION: This study provides new information regarding the possible immunomodulatory effects of CpG ODN in vivo via an IFN-α/β receptor-mediated paracrine pathway

Cell-mediated cytotoxicity-supporting activity of various human gammaglobulin preparations.

Antibody activity, especially that involved in the reaction of antibody-dependent cell-mediated cytotoxicity (ADCC), of five commercially available human gammaglobulin preparations (standard, pepsin-treated, plasmin-treated, polyethylene glycol-fractionated and S-sulfonated gammaglobulin) was measured. All these gammaglobulin preparations had high titers of hemagglutination inhibition and neutralizing antibody against measles virus. In ADCC reaction, the pepsin-treated gammaglobulin preparation showed no antibody activity. The standard gammaglobulin preparation showed weak activity only when highly diluted. The remaining three preparations showed high activity. Though the S-sulfonated gammaglobulin preparation showed no activity in ADCC reaction, it showed high activity after reconversion by means of oxidation and reduction in vitro. The plasmin-treated gammaglobulin preparation showed greater activity than the polyethylene glycol-fractionated preparation of the optimal concentration. In ADCC tests using the plasmin-treated gammaglobulin preparation, K cell activity was strongly inhibited by Hg (thimerosal), while, in those using the standard gammaglobulin preparation, the activity was hardly influenced by Hg, suggesting that the low ADCC activity of the standard gammaglobulin preparation of high concentrations was due to the inhibitory effect of aggregated immunoglobulin G molecules.</p

Presence of Eosinophils in Nasal Secretion during Acute Respiratory Tract Infection in Young Children Predicts Subsequent Wheezing within Two Months

Background: In young children with wheezing or bronchiolitis, especially with respiratory syncitial virus, blood eosinophilia and a high eosinophil cationic protein level in nasal secretions predicts subsequent wheezing in later childhood. However, whether eosinophil activation results from virus-induced inflammation or local eosinophilia per se precedes the onset of wheezing remains unknown. In the present study, we examined the association between the presence of nasal eosinophils during respiratory tract infection (RTI) and subsequent wheezing in young children. Methods: A total of 35 young children less than 3 years of age who visited our outpatient clinic with rhinorrhea between April and July 2004 were enrolled in this prospective cohort study. Subjects who were given diagnoses of allergic rhinitis were excluded. In all the subjects, the presence of eosinophils in nasal secretions was determined. The subjects were followed, and the cumulative incidences of wheezing during the subsequent 2- and 12-month periods were examined. Results: According to a logistic regression analysis adjusted for age, sex, family history, allergies, and wheezing at entry, young children with nasal eosinophil infiltration during acute RTI had a significantly higher risk of wheezing during the subsequent 2 months, compared with those without nasal eosinophil infiltration (adjusted odds ratio, 27.618, p = 0.016). Conclusions: Our findings not only suggest that nasal eosinophil testing may serve as a convenient clinical marker for identifying young children at risk for subsequent wheezing, but also shed new light on the role of eosinophils in the onset of wheezing in young children

Symptoms of Allergic Rhinitis in Women during Early Pregnancy Are Associated with Higher Prevalence of Allergic Rhinitis in Their Offspring

Background: Epigenetic control of gene expression profiles is a ubiquitous mechanism during cell differentiation, organogenesis and chronic inflammatory reactions. Recent studies have shown that allergen exposure during very early pregnancy increases bronchial hypersensitivity in offspring in a murine model of bronchial asthma. However, no such phenomena were reported in humans. In the present study, the role of epigenetic control in the onset of allergic diseases was investigated. Methods: A total of 400 pairs of mothers with physician-diagnosed allergic rhinitis (AR) and their offspring (age 7-18 months) who participated in a large-scale medical check-up were enrolled in this retrospective cohort study. Family history of allergic diseases and the presence or absence of AR symptoms during pregnancy were inquired about using a self-answered questionnaire. A logistic regression model adjusted for age, gender, birth month and father's history of allergic diseases was statistically analyzed. Results: Offspring whose mothers had any AR symptoms during early pregnancy showed a significantly higher adjusted odds ratio for the onset of AR in offspring than those whose mothers had no symptoms during pregnancy (adjusted Odds Ratio: 6.26, p=0.036). However, the symptoms of AR during late pregnancy showed no effects on the odds ratio. In contrast, the presence or absence of AR symptoms during early or late pregnancy showed no association with the prevalence of food allergy, atopic dermatitis or asthma in offspring. Conclusions: Our results suggest the presence of possible epigenetic mechanisms regulating the onset of AR in humans presumably through increased organ-specific hypersensitivity