Scientific Publications

HuProt DNA RNA: The therapeutic value of targeted therapies in patients with lung cancer is reduced when tumours acquire secondary resistance after an initial period of successful treatment. However, the molecular events behind the resistance to targeted therapies in lung cancer remain largely unknown.

• Link: https://onlinelibrary.wiley.com/doi/10.1002/ctm2.1129

The use of immune checkpoint inhibitors (ICIs) has evolved rapidly with unprecedented treatment benefits being obtained for cancer patients, including improved patient survival. However, over half of the patients experience immune related adverse events (irAEs) or toxicities, which can be fatal, affect the quality of life of patients and potentially cause treatment interruption or cessation. Complications from these toxicities can also cause long term irreversible organ damage and other chronic health conditions. Toxicities can occur in various organ systems, with common observations in the skin, rheumatologic, gastrointestinal, hepatic, endocrine system and the lungs.

• Link: https://www.frontiersin.org/articles/10.3389/fimmu.2022.991433/full

HuProt Autoantibodies: Patients with inborn errors of the alternative NF-κB pathway have low thymic AIRE expression, leading to the development of auto-Abs neutralizing type I IFNs, and severe viral diseases.

• Link: https://www.authorea.com/users/573764/articles/617933-impaired-thymic-aire-expression-underlies-autoantibodies-against-type-i-ifns-in-humans-with-inborn-errors-of-the-alternative-nf-kb-pathway

This study aims to discover novel autoantibodies against tumor-associated antigens (TAAs) and establish diagnostic models for assisting in the diagnosis of lung cancer and discrimination of pulmonary nodules (PNs). Ten autoantibodies to TAAbs (TAAbs) were discovered by means of protein microarray and their serum level was also higher in 212 LC patients than that in 212 NC of validation cohort 1 (P < 0.05). The model 1 comprising 4 TAAbs and CEA reached an AUC of 0.813 (95%CI: 0.762–0.864) for diagnosing LC from normal individuals.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S152166162200287X?via%3Dihub

Monoamine oxidase A (MAO A) is the critical enzyme to degrade serotonin in the brain and the knockout mouse exhibits hyperserotonemia and abnormalities that are observed in autism spectrum disorder (ASD). Thus, the MAO A knockout mouse is a valuable model for studying neurological and behavioral impairments in ASD. Based on the immune dysfunction hypothesis, dysregulated humoral immunity may cause neurological impairments.

• Link: https://www.sciencedirect.com/science/article/abs/pii/S0889159122004068?via%3Dihub

Mutations in NOTCH3 underlie cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common inherited cerebral small vessel disease. Two cleavages of NOTCH3 protein, at Asp80 and Asp121, were previously described in CADASIL pathological samples. Using monoclonal antibodies developed against a NOTCH3 neoepitope, we identified a third cleavage at Asp964 between an Asp-Pro sequence. We characterized the structural requirements for proteolysis at Asp964 and the vascular distribution of the cleavage event. A proteome-wide analysis was performed to find proteins that interact with the cleavage product.

• Link: https://www.jbc.org/article/S0021-9258(22)01215-7/fulltext#%20

HuProt Autoantibodies: Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as autoantibodies are generally lacking. Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte-specific lipid droplet protein perilipin 1 (PLIN1) in a murine model of autoimmune polyendocrine syndrome type 1 (APS1). We then tested for PLIN1 autoantibodies in human subjects with acquired lipodystrophy with two independent severe breaks in immune tolerance (including APS1) along with control subjects using a specific radioligand binding assay and indirect immunofluorescence on fat tissue.

• Link: https://diabetesjournals.org/diabetes/article/72/1/59/147096/Autoantibodies-to-Perilipin-1-Define-a-Subset-of

Background: IgM and IgG autoantibodies are present in healthy humans and there are also unique autoantibodies that make up the majority of autoantibodies present in the human body. The primary objective of this study was to identify proteins that are consistently expressed at baseline levels in healthy patients, with the intention of establishing a set of shared or common proteins that can be targeted for further investigation in future research endeavors.

• Link: https://elischolar.library.yale.edu/ysphtdl/2315/

HuProt Autoantibodies: The identification of the high-efficiency and non-invasive biomarkers for hepatocellular carcinoma (HCC) detection is urgently needed. This study aims to screen out potential autoantibodies to tumor-associated antigens (TAAbs) and to assess their diagnostic value for HCC. Fifteen potential TAAbs were screened out from the Human Proteome Microarray by 30 HCC sera and 22 normal control sera, of which eight passed multiple-stage validations by ELISA with a total of 1625 human serum samples from normal controls (NCs) and patients with HCC, liver cirrhosis, chronic hepatitis B, gastric cancer, esophageal cancer, and colorectal cancer.

• Link: https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13371

Immunosenescence is a progressive remodeling of immune functions with a multifactorial etiology including aging and chronic antigenic stressors (inflammation, infections, cancer). We showed that a high pretreatment SIP (CD28–CD57+KLRG1+CD8+ circulating T cells>39.5%, SIP+) was associated with resistance to ICB in patients with aNSCLC. Chronic viral infections may speed up immune aging, especially CMV which affects blood T cells phenotype (loss of CD28, overexpression of CD57). We aimed to assess antiviral serological profile and its association with SIP status.

• Link: https://www.esmoiotech.org/article/S2590-0188(22)00056-9/fulltext#%20