Background: The discovery and development of novel biomarkers that could facilitate early diagnosis and thus prevent the progression of atherosclerosis-related diabetes mellitus (DM), cerebral infarction (CI), and cardiovascular disease (CVD) has garnered much research interest. Notably, recent reports have described a number of highly sensitive antibody markers. In this study, we aimed to identify additional antibody markers that would facilitate screening. Methods:The amplified luminescent proximity homogeneous assay (AlphaLISA) method, which incorporates glutathione-or streptavidin-donor beads and anti-human-IgG-acceptor beads, was used to evaluate serum antibody levels in serum samples. The protein array method was used for the initial screening, and peptide arrays were used to identify epitope sites. Results:The protein array identified SH3 domain-binding protein 5 (SH3BP5) as a target antigen of serum IgG antibodies in the sera of patients with atherosclerosis. We prepared recombinant glutathione S-transferase (GST)-fused SH3BP5 protein. Peptide arrays revealed that the epitope site recognized by serum antibodies is located within amino acids 161-174 of SH3BP5. AlphaLISA revealed significantly higher serum antibody levels against both the SH3BP5 protein and peptide in patients with DM, acute-phase CI, transient ischemic attack, CVD or chronic kidney disease (CKD), than in healthy donors. Furthermore, areas under the receiver operating characteristic curves of these antibodies were higher in patients with CKD and DM than in other patients. Spearman correlation analysis revealed associations between the serum antibody levels against SH3BP5 peptide and artery stenosis, hypertension, and smoking. Conclusions:The serum anti-SH3BP5 antibody marker appears to be useful for estimating the progress of atherosclerosis and may discriminate atherosclerosis associated with hypertension and/or habitual smoking.

For the treatment of atopic dermatitis, a variety of therapies are used including folk medicine. At present, there is no single treatment which is effective to cure the symptoms of atopic dermatitis completely in all patients. We are drawing attention to the high isolation rate of Staphylococcus aureus when starting disinfectant treatment combined with topical steroid therapies for the purpose of killing S. aureus. As a result, we examined many patients in whom almost a complete remission was obtained even after short periods of therapy, though it had been difficult to obtain improvement by conventional treatments. In many patients, IgE values and reagin antibody titer decrease dramatically soon after starting treatment. As a disinfectant, 10% povidone-iodine solution was used. We investigated also the effect of iodine contained in the povidone-iodine solution on the thyroid gland.

Atopic dermatitis (AD) is frequently associated with intestinal and cervical lesions. Staphylococcus aureus produces many kinds of toxins, the bacterial superantigens. The detection rate of toxins was 80.1% from 196 S. aureus strains. Neurological examinations revealed abnormalities in 59 out of 81 AD patients. Cervical magnetic resonance imaging (MRI) was performed in 46 patients randomly and showed abnormal findings in 38 of these patients. In 23 patients who underwent MRI and duodenal biopsy, 3 were found to be normal neurologically and 2 patients showed normal duodenal tissue. However, 18 patients had abnormal findings both on neurological examination and in duodenal tissue. Serial duodenal biopsy tests were performed in 10 AD patients. In 5 patients, the findings of chronic duodenitis disappeared after the therapy with povidone-iodine. These data indicate that the therapy was effective not only for the skin lesions, but improved gastrointestinal tract lesions and cervical myelopathy, by eradicating bacterial superantigens.

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The combination of the local disinfection therapy against Staphylococcus aureus with the conventional therapy for atopic dermatitis has been widely used, and the improvement in skin lesions has been reported to be associated with a remarkable decrease in IgE levels and reagin antibody titers. We have already reported that affected organs were not only the skin but also the gastrointestinal tract in a case with atopic dermatitis. In the present study, the duodenal tissues were examined by biopsy in 32 patients with atopic dermatitis, and mild or chronic duodenitis was observed in all samples. Toxins were examined by PCR from 180 Staphylococcus aureus strains obtained from our patients. The detection rate of toxins was 82.8%. In many patients, antitoxin IgE antibody titers corresponding to their types of toxin and IgE levels were decreased in a parallel manner as time passed. We found 1 patient who complained of paresthesia in all four limbs, and her neurological and radiological examinations showed moderate cervical spondylosis. Neurological examinations revealed some abnormalities in 43 out of 50 patients with atopic dermatitis, such as hyperreflexia of the legs. Cervical MRI was carried out randomly and showed abnormal findings in 21 of 25 patients, in whom 18 duodenal tissues were examined by biopsies.