Publications

Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1), and mucosal immune dysregulation (IL-17A, CCL20, and CCL28).

• Link: https://www.cell.com/cell/fulltext/S0092-8674(20)31231-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420312319%3Fshowall%3Dtrue#%20

Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. Here we show that B-cell repertoire sequencing of 102 clinical gastric cancers and molecular biological analyses unexpectedly reveal that the major humoral cancer antigens are not case-specific neo-antigens but are rather commonly identified as ribonucleoproteins (RNPs) in the focal adhesion complex. These common antigens are shared as autoantigens with multiple autoimmune diseases, suggesting a direct molecular link between cancer- and auto-immunity on the focal adhesion RNP complex.

• Link: https://www.nature.com/articles/s42003-020-01305-5

HuProt Small Molecule: Oxidative stress from elevated reactive oxygen species (ROS) has been reported to induce cell apoptosis and may provide a means to target cancer cells. Celastrol is a natural bioactive compound that was recently shown to increase ROS levels and cause apoptosis in cancer cells. However, the underlying mechanism for this cytotoxic action remains unclear and direct molecular targets of Celastrol have not been identified.

• Link: https://www.thno.org/v10p10290.htm

HuProt Autoantibodies: This brief report details the measurement and identification of IgA antibodies to tropomyosin in a case of presumed ocular myositis with paraspinal myositis in a patient with metastatic uveal melanoma treated with checkpoint inhibitors. High-throughput functional protein microarray analysis and pathway analysis was conducted to identify IgG and IgA antibodies of interest. Antibody levels were compared to generic antibody screening results and levels of the antibodies in a cohort of melanoma patients without myositis (n = 100) at baseline prior to undergoing immunotherapy. The finding of specific muscle antibodies in this clinical case indicates the pathogenic potential of anti-tropomyosin IgA in the development of checkpoint inhibitor associated myositis.

• Link: https://www.tandfonline.com/doi/full/10.1080/2162402X.2020.1804703

The majority of variation in outcome following severe traumatic brain injury (TBI) remains unexplained by currently recognised prognostic factors, suggesting a contribution from unaccounted variables. One key candidate variable is neuroinflammation, including the generation of autoantibodies against brain specific antigens which have been described in some individuals following TBI. Here we hypothesised that autoantibody responses following TBI would differ between individuals, and would explain a proportion of outcome variance.

• Link: https://www.medrxiv.org/content/10.1101/2020.07.24.20161786v1

Alpha-fetoprotein (AFP) is a widely used biomarker for hepatocellular carcinoma (HCC) early detection. However, low sensitivity and false negativity of AFP raise the requirement of more effective early diagnostic approaches for HCC.

• Link: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00918-x

HuProt Autoantibodies: Kawasaki disease (KD) is the leading cause of childhood acquired heart disease in developed nations and can result in coronary artery aneurysms and death. Clinical and epidemiologic features implicate an infectious cause but specific antigenic targets of the disease are unknown. Peripheral blood plasmablasts are normally highly clonally diverse but the antibodies they encode are approximately 70% antigen-specific 1–2 weeks after infection.

• Link: https://academic.oup.com/jid/article/222/1/158/5734989

To characterize the role of B cells on human papilloma virus (HPV)-associated cancer patient outcomes and determine the effects of radiation and PD-1 blockade on B-cell populations.

• Link: https://aacrjournals.org/clincancerres/article/26/13/3345/82679/B-Cells-Improve-Overall-Survival-in-HPV-Associated

HuProt Enzyme: Proteasome inhibitors have provided a significant advance in the treatment of multiple myeloma (MM). Consequently, there is increasing interest in developing strategies to target E3 ligases, de-ubiquitinases, and/or ubiquitin receptors within the ubiquitin proteasome pathway, with an aim to achieve more specificity and reduced side-effects. Previous studies have shown a role for the E3 ligase HUWE1 in modulating c-MYC, an oncogene frequently dysregulated in MM. Here we investigated HUWE1 in MM.

• Link: https://www.nature.com/articles/s41388-020-1345-x

Immune checkpoint inhibitors (ICIs), e.g., ipilimumab (IPI) and/or nivolumab (NIVO), produce durable survival benefit in a substantial proportion of melanoma patients but can also induce severe immune-related adverse events (irAEs) requiring treatment discontinuation. There is no biomarker to predict irAEs in ICI-treated melanoma patients. Given the similar clinical manifestation between irAEs and autoimmune disorders, we hypothesized that a subset of patients possess a subclinical baseline predisposition to developing irAEs that is characterized by specific autoantibodies (autoAbs).

• Link: https://ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3069