Publications

HuProt Review: Autoimmune diseases are caused by the break-down in self-tolerance mechanisms and can result in the generation of autoantibodies specific to human antigens. Human autoantigen profiling technologies such as solid surface arrays and display technologies are powerful high-throughput technologies utilised to discover and map novel autoantigens associated with disease. This review compares human autoantigen profiling technologies including the application of these approaches in chronic and post-infectious autoimmune disease. Each technology has advantages and limitations that should be considered when designing new projects to profile autoantibodies.

• Link: https://link.springer.com/article/10.1007/s12026-023-09362-8

Esophageal squamous cell carcinoma (ESCC) is one of the fatal malignancies worldwide. It has an increased propensity to metastasize via lymphogenous routes in an early stage. The prognosis of patients with lymph node metastases (LNM) is often worse than that of patients without metastases. Although several factors have been found to influence metastasis, the mechanisms of preference for specific metastatic routes remain poorly understood. Herein, we provide evidence that the intrinsic hypersensitivity of tumor cells to ferroptosis may proactively drive lymphatic metastasis.

• Link: https://www.nature.com/articles/s41419-023-05571-z

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

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

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

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

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/