Shuzo Matsumoto

Severe chronic active Epstein-Barr virus infection syndrome.

Reports of unusually severe lymphoproliferative disorders associated with extremely high antibody titers against Epstein-Barr virus (EBV) have recently increased. The syndrome, which we designated severe chronic active EBV infection syndrome, is characterized by persistent or intermittent fever, lymphadenopathy, and hepatosplenomegaly and primarily affects children and young adults. Polyclonal gammopathy and bone marrow suppression are generally observed, and some patients develop B-cell or T-cell lymphoproliferation or lymphoma. Frequently, EBV genomes are detectable in tissues infiltrated with lymphoid cells. Additionally, it is difficult to establish spontaneous or B95-8 EBV-induced cell lines despite the expression of an activated EBV infection. We review and report here the published medical literature and our own experience regarding patients with severe chronic active EBV infection syndrome in an attempt to understand this enigmatic syndrome and the possible pathogenetic mechanism(s) responsible for this disorder.

IgE and IgG4 antibodies from patients with mite allergy recognize different epitopes of Dermatophagoides pteronyssinus group II antigen (Der p 2)

BACKGROUND Der p 2, composed of 129 amino acids, is one of the major allergens of Dermatophagoides pteronyssinus. Several groups reported epitope mapping of IgE antibody but not of IgG or IgG subclass antibodies in Der p 2. OBJECTIVE The purpose of this study was to compare the epitopes recognized by Der p 2-specific IgE antibodies with those recognized by IgG4 antibodies. METHODS Recombinant fusion proteins containing a full-length peptide or overlapping five fragments of Der p 2 were prepared and analyzed for their reactivity with IgE and IgG subclass antibodies in sera from patients with mite allergy by means of Western blot procedure. RESULTS IgE antibodies in 12 of 13 sera tested bound to full-length Der p 2 (1-129). In 11 of these 12 sera, IgE antibodies bound to one or more of fragments 41-80, 64-105, or 81-129 but not to those of 1-40 or 20-63. Of the 11 sera in which the IgE antibodies to the fragments were detected, only four contained detectable levels of IgG4 antibodies reactive to the fragments. The binding spectra of the IgG4 antibodies against the fragments were rather wide and differed from those of IgE antibodies. CONCLUSION Results revealed that there are differences in epitope recognition between IgE and IgG4 antibodies; IgE antibodies recognize restricted parts of Der p 2 antigen compared with IgG4.

Successful intravenous immunoglobulin therapy for recurrent pneumococcal otitis media in young children.

Serum immunoglobulin levels and naturally occurring antibody titres againstStreptococcus pneumoniae were measured in seven children aged 1–1.9 years with recurent pneumococcal acute otitis media (AOM). Three of them had low IgG2 levels. Mean antibody levels of anti-pneumococcal IgG1 and anti-pneumococcal IgG2 were significantly lower in patients when compared to those of healthy controls and children who had less frequent episodes of AOM. Following treatment with intravenous immunoglobulin (IVIG) for 6 months, anti-pneumococcal IgG1 and IgG2 antibody levels increased and the number of episodes of AOM decreased in all patients. Following the discontinuation of IVIG therapy, no AOM episode occurred. Serum levels of anti-pneumococcal IgG1 and IgG2 were normal, which were measured in three subjects at 5,6, and 12 months after the cessation of IVIG therapy. These results suggested that delayed maturation of anti-pneumococcal antibody production caused recurrent AOM and this condition was corrected by IVIG therapy.

Genetic heterogeneity in patients with X-linked recessive chronic granulomatous disease.

ABSTRACT: Genetic heterogeneity in 12 patients from 11 different families with X-linked recessive chronic granu-kHnatoas disease was studied by Southern blot analysis using cytochrome b heavy-chain cDNA as a probe. We found the abnormal restriction length fragment patterns of the cytochrome b heavy-chain gene in three families, which were not observed in healthy controls. DNA from one patient showed the abnormal patterns after digestion with several restriction enzymes. The DNA of two other patients showed the abnormality only with TaqI and Pst I. Analysis of the same family members indicated that these abnormal patterns cosegregated with the disease. The other nine patients from eight families did not have any abnormalities detectable by Southern blot analysis. Although further experimentation should be done to study the molecular genetic heterogeneity in most X-linked chronic granuloma-tous disease families (eight of 11), we were able to demonstrate at least three different types of mutations hi the cytochrome b heavy-chain gene responsible for the disease.

Sites of Epstein-Barr Virus Replication in Acute and Chronic Active Epstein-Barr Virus Infections

We examined Epstein-Barr virus (EBV) in saliva samples and peripheral blood mononuclear cells (PBMC) from 9 patients with acute infectious mononucleosis (IM) and 4 patients with chronic active EBV infection (CEBV). All saliva samples from patients with acute IM were positive for EBV by both Southern blot hybridization assay and the cord transformation assay. In contrast, EBV DNA could not be detected in saliva samples from patients with CEBV. Only one of the saliva samples from 4 patients with CEBV could transform cord blood lymphocytes with extreme difficulty. No saliva samples from patients with CEBV were capable of inducing early antigens in Raji cells. On the other hand, EBV DNA was detected in PBMC from 3 of the 4 patients with CEBV but not in those from patients with acute IM by Southern blot hybridization. Spontaneous lymphoblastoid cell lines could be easily established from PBMC of patients with acute IM but not from PBMC of patients with CEBV, despite several attempts. Viral capsid antigen and early antigens were not observed in cultured cells from patients with CEBV. These results suggest that the main site of EBV replication in CEBV might not be oropharyngeal epithelial cells.

A Study of the Binding of Immunoglobulin G and Immunoglobulin E from Children with Bronchial Asthma to Peptides Derived from Group II Antigen of Dermatophagoides pteronyssinus

ABSTRACT: The peptides that were produced by the treatment of the purified group II antigen of Dermatophagoides pteronyssinus with cyanogen bromide, lysylendopeptidase, Staphylococcus aureus V8 protease, or n-tosyl-l-phenylalanylchloromethyl ketone-treated trypsin were examined for their binding with IgG and IgE from children with bronchial asthma by immunoblotting analysis. Both IgG and IgE bound to the peptides from the amino terminus to the 76th residue and the carboxyl terminal side from the 13th or 15th residue; on the other hand, both Ig failed to bind to the carboxyl terminal side from the 39th, 56th, or 77th residue. The data demonstrated that peptides lacking residues 1 to 15 possessed the ability to bind Ig, whereas those lacking residues 1 to 39 had lost it. The present study indicates that the amino terminal half of the group II antigen of Dermatophagoides pteronyssinus is more important for the binding of IgG and IgE than the carboxyl terminal half and suggests that the residues 15 to 39 may be directly related to the binding of both IgG and IgE.