Identification of Antibody Against SNRPB, Small Nuclear Ribonucleoprotein-Associated Proteins B and B', as an Autoantibody Marker in Crohn's Disease using an Immunoproteomics Approach.

BACKGROUND: Current non-invasive biomarkers for Crohn's disease are limited in their utility. Progress in identifying individual autoantigens and autoantibodies in Crohn's disease has been challenging due to limitations of available immunoassays. AIMS: Our aim was to identify autoantibodies associated with Crohn's disease that may be useful in diagnosis and management using an innovative protein array technology, namely nucleic acid programmable protein arrays [NAPPA]. METHODS: Serum samples of 96 patients with established Crohn's disease and 96 healthy controls were included and evenly split into discovery and validation sets randomly. Autoantibodies of both IgG and IgA classes were profiled against ~1900 human proteins in the discovery set on NAPPA. Autoantibodies discovered to be Crohn's disease-specific were further validated in the independent validation set by enzyme-linked immunosorbent assay. RESULTS: Overall, reactivity of IgG autoantibodies was stronger than that of IgA autoantibodies; however, IgA autoantibodies showed greater differential reactivity between cases and controls. Four IgA autoantibodies against SNRPB, PRPH, PTTG1 and SNAI1 were newly identified with sensitivities above 15% at 95% specificity, among which anti-SNRPB-IgA had the highest sensitivity of 24.0%. Autoantibodies associated with specific disease subtypes were also found. CONCLUSIONS: As one of the first studies to use immunoproteomics for the identification of autoantibodies in Crohn's disease, our results support the utility of NAPPA in implementing future expanded studies with better coverage of the human proteome and microbial proteomes relevant to Crohn's disease and identifying antibody markers that may have clinical impact in diagnosis and management.

Novel antigens in non-small cell lung cancer: SP17, AKAP4, and PTTG1 are potential immunotherapeutic targets.

Lung cancer is the leading cause of cancer deaths in both genders worldwide, with an incidence only second to prostate cancer in men and breast cancer in women. The lethality of the disease highlights the urgent need for innovative therapeutic options. Immunotherapy can afford efficient and specific targeting of tumor cells, improving efficacy and reducing the side effects of current therapies. We have previously reported the aberrant expression of cancer/testis antigens (CTAs) in tumors of unrelated histological origin. In this study we investigated the expression and immunogenicity of the CTAs, Sperm Protein 17 (SP17), A-kinase anchor protein 4 (AKAP4) and Pituitary Tumor Transforming Gene 1 (PTTG1) in human non-small cell lung cancer (NSCLC) cell lines and primary tumors. We found that SP17, AKAP4 and PTTG1 are aberrantly expressed in cancer samples, compared to normal lung cell lines and tissues. We established the immunogenicity of these CTAs by measuring CTA-specific autoantibodies in patients' sera and generating CTA-specific autologous cytotoxic lymphocytes from patients' peripheral blood mononuclear cells. Our results provide proof of principle that the CTAs SP17/AKAP4/PTTG1 are expressed in both human NSCLC cell lines and primary tumors and can elicit an immunogenic response in lung cancer patients.