Tomoki Yoshizaki

Increase in B-cell-activation factor (BAFF) and IFN-γ productions by tonsillar mononuclear cells stimulated with deoxycytidyl-deoxyguanosine oligodeoxynucleotides (CpG-ODN) in patients with IgA nephropathy

IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is recognized as a tonsil-related diseases since it often gets worse after and/or during acute tonsillitis and the disease progression is often prevented by tonsillectomy. Although several reports showed an increase in IgA production of tonsillar mononuclear cells (TMCs), its mechanism has not yet been fully clarified. Recently, B-cell-activation factor (BAFF), which stimulates B-cell proliferation and immunoglobulin production, was identified. Unmethylated deoxycytidyl-deoxyguanosine oligodeoxynucleotide (CpG-ODN), which is able to mimic the immunostimulatory activity of microbial DNA, is known to be involved in the production of immunoglobulins and some cytokines. In this study, we focused on roles of BAFF and IFN-gamma in IgA production of TMCs stimulated with CpG-ODN in IgAN patients. Two-color flow cytometric analysis revealed that the intercellular expression of IFN-gamma on the T-cells freshly isolated from tonsils was significantly higher in IgAN patients than in non-IgAN patients (p=0.032). The spontaneous productions of IgA and IFN-gamma of TMCs were significantly higher in IgAN patients than in non-IgAN patients (p=0.023 and p=0.02). Under stimulation with CpG-ODN, the productions of IgA, BAFF and IFN-gamma of TMCs were significantly higher in IgAN patients than in non-IgAN patients (p=0.013, p=0.005 and p=0.039). The IgA production of TMCs stimulated by CpG-ODN was inhibited by the treatment with anti-BAFF antibody and/or anti-IFN-gamma antibody. Under stimulation with IFN-gamma, the BAFF expression on the CD1c cells and the BAFF production of TMCs were significantly higher in IgAN patients than in non-IgAN patients (p=0.004 and p=0.042). These data suggest that hyper-immune response to microbial DNA may be present in IgAN patients and may lead to hyperproduction of BAFF up-regulated by IFN-gamma, resulting in hyperproduction of IgA in IgAN patients.

Up-regulation of CC chemokine receptor 6 on tonsillar T cells and its induction by in vitro stimulation with α-streptococci in patients with pustulosis palmaris et plantaris

Pustulosis palmaris et plantaris (PPP) is a tonsil‐related disease; tonsillectomy is somewhat effective in treating the condition. However, the aetiological association between the tonsils and PPP has not yet been elucidated fully. Recently, some chemokines and chemokine receptors, including CC chemokine receptor (CCR) 4, CCR6 and CX chemokine receptor (CXCR) 3, have been reported to play important roles in the development of psoriasis, a disease related closely to PPP. In this study, we found that CCR6 expression on both tonsillar and peripheral blood T cells was up‐regulated more intensively in PPP patients than in non‐PPP patients (P < 0·001 for both), but CCR4 and CXCR3 expressions were not. In vitro stimulation with α‐streptococcal antigen enhanced CCR6 expression significantly on tonsillar T cells in PPP patients (P < 0·05), but this was not observed in non‐PPP patients. The chemotactic response of tonsillar T cells to the CCR6 ligand CC chemokine ligand (CCL) 20 was significantly higher in PPP patients than in non‐PPP patients (P < 0·05). The percentage of CCR6‐positive peripheral blood T cells decreased after tonsillectomy in PPP patients (P < 0·01); this decrease correlated with an improvement of skin lesions (P < 0·05, r = −0·63). The numbers of CCR6‐positive cells and the expression of CCL20 were increased significantly in pathological lesions compared with non‐pathological lesions in PPP skin (P < 0·01, P < 0·05 respectively). These results suggest that a novel immune response to α‐streptococci may enhance CCR6 expression on T cells in tonsils and that CCR6‐positive T cells may move to peripheral blood circulation, resulting in recruitment to target skin lesions expressing CCL20 in PPP patients. This may be one of the key roles in pathogenesis of the tonsil‐related disease PPP.

Laryngeal plexiform schwannoma as first symptom in a patient with neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder characterized by bilateral vestibular schwannomas. The initial symptoms of NF2 are usually hearing loss and tinnitus caused by vestibular schwannomas. Although other intracranial, spinal, or skin tumors also occur in NF2, laryngeal lesions are very rare. We report a rare case of NF2 with laryngeal plexiform schwannoma as first symptom. A 38-year-old man presented with a smooth-surfaced submucosal supraglottic mass. Two round masses in the left chest wall and left supraclavicular fossa were noted incidentally during investigation of the laryngeal mass. Magnetic resonance imaging (MRI) findings for these masses were identical to those of the laryngeal mass. No typical symptoms related to NF2 were identified. Histologically, the laryngeal tumor represented plexiform schwannoma. We thus considered that the two round masses in the left chest wall and left supraclavicular fossa might also represent plexiform schwannomas. NF2 was suspected, as a high incidence of multiple plexiform schwannomas has been suggested for patients with NF2. MRI of brain lesions demonstrated bilateral vestibular schwannomas and multiple meningiomas. Finally, NF2 with laryngeal plexiform schwannoma was diagnosed. Recognizing that multiple plexiform schwannomas could be associated with NF2 is important.

Selective expansion of T cell receptor (TCR) V beta 6 in tonsillar and peripheral blood T cells and its induction by in vitro stimulation with Haemophilus parainfluenzae in patients with IgA nephropathy

IgA nephropathy (IgAN), the most common form of primary glomerulonephritis, is recognized as a disease that often becomes worse during acute tonsillitis. Although many reports have shown that tonsillectomy is an effective treatment for IgAN patients, the immunological evidence has not yet been investigated fully. In this study, we compared the expression of T cell receptor (TCR) V beta families in tonsillar T cells of IgAN patients to those of non‐IgAN patients. The reverse transcription–polymerase chain reaction (RT–PCR) and flow cytometric analyses showed that the TCR V beta 6 was used more frequently in tonsillar T cells of IgAN patients than in those of non‐IgAN patients (P < 0·01 each). Similarly, the proportions of TCR V beta 6‐positive cells in peripheral blood T cells were significantly higher in IgAN patients than in non‐IgAN patients (P < 0·05). After tonsillectomy, the proportions decreased in IgAN patients (P < 0·05), but did not in non‐IgAN patients. Furthermore, in vitro stimulation with Haemophilus parainfluenzae antigen, which is reported to deposit in the glomerular mesangium of IgAN, enhanced expression of TCR V beta 6 in tonsillar T cells from both IgAN and non‐IgAN patients. These results suggest that TCR V beta 6‐positive tonsillar T cells might be activated by H. parainfluenzae, move into the kidney through blood circulation and induce glomerulonephritis.

Up-Regulation of ß1 Integrin on Tonsillar T Cells and its Induction by In Vitro Stimulation with α-streptococci in Patients with Pustulosis Palmaris et Plantaris

Pustulosis palmaris et plantaris (PPP) is a tonsil-related disease that can be cured with tonsillectomy. Recent immunological studies have shown that hyperactivation of tonsillar T cells is caused by a hyperimmune response to α-streptococci; recruitment of the T cells to lesions may be involved in the pathogenesis of PPP. ß1 integrin, expressed on T cells, not only provides a costimulatory signal for T-cell activation but also facilitates the accumulation of T cells in inflammatory skin lesions. In this study, we found that expression of ß1 integrin on both tonsillar and peripheral blood CD4-positive T cells was higher in PPP patients than in non-PPP patients. In vitro stimulation with α-streptococcal antigen significantly enhanced ß1 integrin expression on tonsillar CD4-positive T cells in PPP patients, but not in non-PPP patients. The chemotactic response of tonsillar CD4-positive T cells to vascular cell adhesion molecule-1, the ß1 integrin ligand, was significantly better in PPP patients than in non-PPP patients. The percentage of ß1 integrin-positive peripheral blood CD4-positive T cells decreased after tonsillectomy in PPP patients. The numbers of ß1 integrin-positive T cells and the expression of vascular cell adhesion molecule-1 were more elevated in plantar PPP skin lesions than in normal skin. These results suggest that ß1 integrin may play a key role in the pathogenesis of PPP.

Recent Changes in Nasopharyngeal Flora of Children in Japan

We investigated the relationship between nasopharyngeal flora of pediatric patients and antibiotic consumption in a local community in Japan between 2000 and 2009 retrospectively. There was a clear relationship between the lower annual consumption rate of cephalosporins and the lower annual prevalence of non-susceptible strains of Streptococcus pneumoniae (SP). High prevalence of BLNAR (β-lactamase nonproducing ampicillin-resistant Haemophilus influenzae) has been one of the bacteriological features of Japan.

Long-term Results of Tonsillectomy in Children

We retrospectively analyzed 289 children who underwent tonsillectomy for recurrent tonsillitis and/or obstructive sleep apnea syndrome (OSAS). The analysis revealed that the number of times of postoperative pharyngitis and exothermic degree were markedly improved in patients with recurrent tonsillitis, and as a result, the number of days absent from school decreased. In patients with OSAS, snoring and sleep apnea symptoms were improved markedly and immediately after tonsillectomy. Patient satisfaction was extremely high in both recurrent tonsillitis and OSAS, and we found postoperative bleeding, as a postoperative complication, only in 6 cases (2%).Tonsillectomy for recurrent tonsillitis and OSAS in children was extremely effective and safely.

Mechanisms on the Development of Tonsillar Focal Infections

Pustulosis palmaris et plantaris (PPP), Sterno-costo-claviclar hyperostosis (SCCH), IgA nephropathy, and some other autoimmune diseases have been regarded as tonsillar focal infections since tonsillectomy is quite effective in the treatment of these diseases. In this paper, we reviewed recent clinicopathological evidence on tonsillar focal infections obtained through our experience as well as in the literature. In addition, we summarized experimental results regarding mechanisms of the development and progression of tonsillar focal infections. It has been speculated that abnormal immune responses in the tonsils may cause or worsen the disease. Therefore, tonsillectomy should be recommended for the treatment of tonsillar focal infections.

Castleman's Disease of the Neck : A Case Report

Castlemans disease was first reported by Castlemann et al. in 1954 as localized large benign hyperplastic mediastinal lymph nodes histologically characterized by hyperplasia of lymphoid follicles and capillary proliferation with endothelial hyperplasia. In 1972, Keller et al. subsequently divided Castlemans disease into two types according to the pathologic findings: the hyaline-vascular type and the plasma cell type. We report a case of hyaline-vascular type of Castlemans disease in a 29-year-old female.The patient presented with 11 years history of a large tumor on the right side of her neck. The tumor size had not increasad for 11 years and she had no symptoms except for neck swelling. CT and MRI showed a single mass (60×50×30mm), and laboratory data were within normal ranges. The tumor was surgically resected and histologically identified as a hyaline-vascular type of Castlemans disease. Postoperatively the patient is well with no recurrence for one year.