Squamous Cell Carcinoma Antigen 2 (SCCA2, SERPINB4): An Emerging Biomarker for Skin Inflammatory Diseases.

Squamous cell carcinoma antigens 1 and 2 (SCCA1 and 2, SERPIN B3 and B4), members of the ovalbumin serpin (ov-serpin)/clade B serpin family, were originally discovered as tumor-specific antigens and are used as tumor markers for various kinds of squamous cell carcinomas. Recently, our understanding of the underlying mechanisms of how SCCA1/2 enhance tumor growth has greatly increased. Moreover, it has been shown that SCCA1/2 are involved in the pathogenesis of several inflammatory diseases: asthma, psoriasis, and atopic dermatitis (AD). IL-22 and IL-17, signature cytokines of type 17 inflammation, as well as IL-4 and IL-13, signature cytokines of type 2 inflammation, both of which are positively correlated with the pathogenesis of psoriasis and allergic diseases, respectively, can induce expression of SCCA1/2 in airway epithelial cells and/or keratinocytes, leading to high expression of SCCA1/2 in these diseases. Based on these findings, several trials have been performed to examine the potential of applying SCCA1/2 to biomarkers for these diseases. The findings show that SCCA2 is useful to aid diagnosis, estimate clinical severity and disease type, and assess responses to treatment in psoriasis and AD. These results suggest that SCCA2 has emerged as a novel biomarker for skin inflammatory diseases.

[Establishment of a diagnostic system for allergic diseases aiming at personalized medicine--establishment of a novel ELISA system for SCCA].

It is known that IL-13, a Th2-type cytokine, is critical for the onset of bronchial asthma, and therefore, various anti-IL-13 antagonists are now being developed as reagents for treating asthma patients. However, there is no good way to select allergic patients into who such IL-13 antagonists should be administered. We previously found that squamous cell carcinoma antigens (SCCAs) 1 and 2 were IL-13-inducible gene products in bronchial epithelial cells and that serum SCCA level was elevated in the patients of bronchial asthma and atopic dermatitis. In this study, we tried to establish specific ELISA systems for SCCA1 and SCCA2. We generated several hybridoma clones secreting rat or mouse antibodies recognizing specifically SCCA1 or SCCA2, or both. By combining two among these antibodies, we found that the ELISA systems using rat anti-SCCA2 antibody (SS14B) as the coated antibody and rat-SCCA1 antibody (SS11G) or rat-SCCA2 antibody (SS8G) as the primary antibodies showed with high sensitivities specific recognition of SCCA1 and SCCA2, respectively. These results demonstrated that we could establish the specific ELISA system for SCCA1 and SCCA2. These specific ELISA systems for SCCA1 and SCCA2 are useful to analyze the correlation between serum SCCA level and the pathogenesis of allergic diseases and have a potential to apply to enforcement of the personalized medicine for allergic diseases.

[Development of testing kits of anti-ganglioside antibody: clinical utility in Guillain-Barré and Fisher syndromes].

We developed testing kits for anti-GM1 and anti-GQ1b IgG antibodies and examined their utilities in supporting the diagnosis of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS). Anti-GM1 antibody was detected in 49% of 95 patients with GBS and in 5% or less of disease and normal controls. Anti-GQ1b antibody was detected in 85% of 55 patients with FS, whereas in none of the controls. Eight GBS patients, in whom anti-GM1 IgG antibody was judged negative using the kit, were found to have other anti-ganglioside IgG antibodies. Four of them showed ophthalmoplegia and had anti-GQ1b IgG antibody. Detection of anti-GM1 IgG antibody in GBS and of anti-GQ1b IgG antibody in FS within one week after the disease onset were significantly more frequent compared to albuminocytologic dissociation in the cerebrospinal fluids (GBS, 58% vs 32%; FS, 89% vs 20%). These findings indicate that our testing kits are useful for supporting the early diagnosis of GBS and FS.

Surfactant-based homogeneous assay for the measurement of triglyceride concentrations in VLDL and intermediate-density lipoprotein.

BACKGROUND: Existing studies have demonstrated the clinical significance of triglyceride content in VLDL (VLDL-TG) and intermediate-density lipoprotein (IDL-TG). We developed a homogeneous assay protocol to directly measure VLDL-TG. METHODS: Possible reagents and conditions for measuring VLDL-TG were comprehensively tested, and the "best" combination was determined. Healthy persons were instructed to consume a fatty meal after 15-h overnight fasting. Serum VLDL-TG + IDL-TG concentrations were measured using the proposed method. Patients with serum LDL-cholesterol concentrations > or = 3.62 mmol/L (140 mg/dL) were administered simvastatin at a daily dose of 5 mg, and serum VLDL-TG concentrations were then measured. RESULTS: The combination of 2 nonionic surfactants played an important role in differentiating VLDL and IDL from other lipoproteins, probably via specific interactions with phospholipids and apolipoproteins. The regression line of the proposed method (y) and the ultracentrifugal assay (x) was: y = 0.98x + 0.31 mmol/L (r = 0.98; n = 73; P < 0.05). The difference between postprandial total TG and VLDL-TG concentrations was statistically significant (P < 0.05). After 8 weeks of therapy with simvastatin, total TG and LDL-cholesterol concentrations were 13.6% and 26.3% lower, respectively (P < 0.05), whereas VLDL-TG did not show any significant decrease. CONCLUSION: Our homogeneous method can measure TG content in VLDL and IDL.