Mayumi Wada

Autoantibody Profile Differentiates between Inflammatory and Noninflammatory Bullous Pemphigoid

Bullous pemphigoid (BP) is a major autoimmune blistering skin disorder, in which a majority of the autoantibodies (autoAbs) target the juxtamembranous extracellular noncollagenous 16A domain (NC16A) domain of hemidesmosomal collagen XVII. BP-autoAbs may target regions of collagen XVII other than the NC16A domain; however, correlations between epitopes of BP-autoAbs and clinical features have not been fully elucidated. To address correlations between the clinical features and specific epitopes of BP-autoAbs, we evaluated the epitope profiles of BP-autoAbs in 121 patients. A total of 87 patients showed a typical inflammatory phenotype with erythema and autoAbs targeting the anti-NC16A domain, whereas 14 patients showed a distinct noninflammatory phenotype, in which autoAbs specifically targeted the midportion of collagen XVII, but not NC16A. Interestingly, this group clinically showed significantly reduced erythema associated with scant lesional infiltration of eosinophils. Surprisingly, 7 of the 14 cases (50.0%) received dipeptidyl peptidase-IV inhibitors for the treatment of diabetes. Dipeptidyl peptidase-IV inhibitors were used in 3 of 76 (3.9%) typical cases of BP with autoAbs targeting NC16A; thus, dipeptidyl peptidase-IV inhibitors are thought to be involved in the development of atypical noninflammatory BP. This study shows that the autoAb profile differentiates between inflammatory and noninflammatory BP, and that noninflammatory BP may be associated with dipeptidyl peptidase-IV inhibitors.

Epitope-Dependent Pathogenicity of Antibodies Targeting a Major Bullous Pemphigoid Autoantigen Collagen XVII/BP180.

In bullous pemphigoid, the common autoimmune blistering disorder, IgG autoantibodies target various epitopes on hemidesmosomal transmembrane collagen XVII (COL17)/BP180. Antibodies (Abs) targeting the extracellular noncollagenous 16th A domain of COL17 may be pathogenic; however, the pathogenic roles of Abs targeting non-noncollagenous 16th A regions are poorly understood. In this study using a pathogenic and a nonpathogenic monoclonal antibody (mAb) targeting the noncollagenous 16th A domain (mAb TS39-3) and the C-terminus domain (mAb C17-C1), respectively, we show that endocytosis of immune complexes after binding of Abs to cell surface COL17 is a key phenomenon that induces skin fragility. Passive transfer of IgG1 mouse mAb TS39-3 but not mAb C17-C1 induces dermal-epidermal separation in neonatal human COL17-expressing transgenic mice. Interestingly, mAb C17-C1 strongly binds with the dermal-epidermal junction of the recipient mice skin, suggesting that binding of Abs with COL17 is insufficient to induce skin fragility. In cultured normal human epidermal keratinocytes treated with these mAbs, mAb TS39-3 but not mAb C17-C1 internalizes immune complexes after binding with cell surface COL17 via macropinocytosis, resulting in reduced COL17 expression. This study shows that pathogenicity of Abs targeting COL17 is epitope dependent, which is associated with macropinocytosis-mediated endocytosis of immune complexes and finally results in the depletion of COL17 expression in basal keratinocytes.

Near-infrared spectroscopic study on the effects of chewing on short-term memory

Using near-infrared spectroscopy, we examined whether chewing gum improves performance in a short-term memory task - immediate recall of random eight-digit numbers - by assessing cerebral hemodynamic response in the prefrontal cortex. We found that the oxyhemoglobin concentration during and after chewing gum was higher than that before chewing; further, the concentration increased during the task, and this increase was reduced with chewing, although non-significantly. Chewing did not improve task performance. Therefore, chewing-induced hemodynamic responses were unrelated to the performance in short-term memory tasks.

Differences in sequential posttreatment salivary IL-6 levels between patients with and patients without locoregional recurrences of oral squamous cell carcinoma: Part III of a cohort study.

OBJECTIVE Sequential postoperative salivary interleukin-6 (IL-6) concentrations were examined in patients with oral squamous cell carcinoma (OSCC) who had early or late locoregional recurrences or those who did not. STUDY DESIGN Twenty-seven consecutive patients with OSCC were originally included in the study. All patients underwent radical surgery. Four saliva samples were collected before (periods I and II) and after (periods III and IV) surgery, and IL-6 concentrations were measured. RESULTS Although postoperative (period III: at the time of discharge) salivary IL-6 level was significantly higher in patients with early locoregional recurrence (P = .02) than in those without, no such relationships were observed for preoperative IL-6 concentrations (periods I and II). Postoperative (period IV: 24 months after surgery) IL-6 level was significantly higher in patients with late locoregional recurrence (P = .03) than in those without, but no such relationships were observed for IL-6 concentrations in periods I, II, and III. CONCLUSIONS Sequential postoperative salivary IL-6 concentration may be a useful marker for diagnosis of early and late locoregional recurrence in OSCC.

G‑CSF producing oral carcinoma with diffuse uptake of FDG in the bone marrow: A case report

A 78-year-old male patient was referred to the Department of Oral Surgery, Hokuto Hospital (Obihiro, Japan) for painless swelling on the left neck and tongue. Histopathological examination of a biopsy specimen resulted in a diagnosis of squamous cell carcinoma of the tongue. Imaging examinations revealed cervical lymph node metastases on both sides, along with diffuse uptake of 18F-fluorodeoxyglucose (FDG) in the bone marrow of the spine and pelvis. Hematologic tests revealed an increased white blood cell (WBC) count and serum concentrations of granulocyte colony stimulating factor (G-CSF). These findings suggested a G-CSF producing tumor, with fluctuations of WBC count, serum G-CSF concentration, and FDG uptake in the bone marrow, associated with tumor shrinkage and enlargement, an indicator of tumor status.

Use of FDG-PET to detect a chronic odontogenic infection as a possible source of the brain abscess

AbstractThis study describes the use of 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to detect a chronic odontogenic infection as the possible origin of a brain abscess (BA). A 74-year-old man with esophageal carcinoma was referred to our department to determine the origin of a BA in his oral cavity. He had no acute odontogenic infections. The BA was drained, and bacteria of the Staphylococcus milleri group were detected. Whole body FDG-PET revealed that the only sites of definite uptake of FDG were the esophageal carcinoma and the left upper maxillary region (SUVmax: 4.5). These findings suggested that the BA may have originated from a chronic periodontal infection. Six teeth with progressive chronic periodontal disease were extracted to remove the possible source of BA. These findings excluded the possibility of direct spread of bacteria from the odontogenic infectious lesion to the intracranial cavity. After extraction, there was no relapse of BA.