Publications

Autoantibodies are self-antigen reactive antibodies that play diverse roles in the normal immune system, tissue homeostasis, and autoimmune and neurodegenerative diseases. Anti-neuronal autoantibodies have been detected in neurodegenerative disease serum, with unclear significance. To identify diagnostic biomarkers of Alzheimer’s disease (AD), we analyzed serum autoantibody profiles of the HuProt proteome microarray using the discovery set of cognitively normal control (NC, n = 5) and AD (n = 5) subjects. Approximately 1.5-fold higher numbers of autoantibodies were detected in the AD group (98.0 ± 39.9/person) than the NC group (66.0 ± 39.6/person).

• Link: https://www.nature.com/articles/s41598-021-04556-2

HuProt Enzyme: Multiple sclerosis (MS) is a heterogenous autoimmune disease in which autoreactive lymphocytes attack the myelin sheath of the central nervous system. B lymphocytes in the cerebrospinal fluid (CSF) of patients with MS contribute to inflammation and secrete oligoclonal immunoglobulins1,2. Epstein–Barr virus (EBV) infection has been epidemiologically linked to MS, but its pathological role remains unclear3. Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM) and provide structural and in vivo functional evidence for its relevance.

• Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9382663/

HuProt Small Molecule: Currently, multiple myeloma (MM) is still an incurable plasma cell malignancy in urgent need of novel therapeutic targets and drugs. AHSA1 expression was increased in MM samples compared to normal controls, which was significantly associated with MM relapse and poor outcomes. Furthermore, AHSA1 promoted MM cell proliferation and proteasome inhibitor (PI) resistance in vitro and in vivo. Mechanism exploration indicated that AHSA1 acted as a co-chaperone of HSP90A to activate CDK6 and PSMD2, which were key regulators of MM proliferation and PI resistance respectively.

• Link: https://jeccr.biomedcentral.com/articles/10.1186/s13046-021-02220-1

HuProt Small Molecule: The serine protease inhibitor Rv3364c of Mycobacterium tuberculosis (MTB) is highly expressed in cells during MTB exposure. In this study, we showed that the 12WLVSKF17 motif of Rv3364c interacts with the BAR domain of SNX9 and inhibits endosome trafficking to interact with p47phox, thereby suppressing TLR4 inflammatory signaling in macrophages. Derived from the structure of this Rv3364c peptide motif, 2,4-diamino-6-(4-tert-butylphenyl)-1,3,5-trazine, DATPT as a 12WLVSKF17 peptide-mimetic small molecule has been identified. DATPT can block the SNX9–p47phox interaction in the endosome and suppress reactive oxygen species and inflammatory cytokine production; it demonstrated significant therapeutic effects in a mouse model of cecal ligation and puncture-induced sepsis.

• Link: https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c01551

HuProt Review: The introduction of multiparametric autoantibody tests has been proposed to improve the accuracy of the immunological diagnosis of autoimmune diseases (AID) and to accelerate time for completing the diagnostic process. Multiplex tests are capable of detecting many autoantibodies in a single run whereas a traditional immunoassay uses a single antigen to detect only a single specificity of autoantibodies. The reasons why multiplex tests could replace conventional immunoassays lie in the evidence that they allow for more efficient handling of large numbers of samples by the laboratory, while ensuring greater diagnostic sensitivity in AID screening.

• Link: https://academic.oup.com/jalm/article/7/1/137/6498239?login=false

HuProt Autoantibodies: Autoantibodies (AAbs) targeted tumor-associated antigens (TAAs) have the potential for early detection of breast cancer. Here, 574 early-stage breast cancer (ES-BC) patients containing 4 subtypes (Luminal A, Luminal B, HER2+, TN), 126 benign breast disease (BBD) patients, and 199 normal healthy controls (NHC) were separated into three-phases to discover, verify, and validate AAbs. In discovery phase using high-throughput protein microarray, 37 AAbs with sensitivity of 31.25%-86.25% and specificity over 73% in ES-BC, and 40 AAbs with different positive rates between subtypes were identified as candidates. In verification phase, 18 AAbs were significantly increased compared with the Control (BBD and NHC) in focused array.

• Link: https://onlinelibrary.wiley.com/doi/10.1111/cas.15227

HuProt Autoantibodies: Hepatocellular carcinoma (HCC) is a malignancy with a dismal survival rate. The novel autoantibodies panel may provide new insights for the diagnosis of HCC. Biomarkers screened by two methods (bioinformatics and the antigen-antibody system) were taken as candidate tumor-associated antigens (TAAs). Enzyme-linked immunosorbent assay was used to detect the corresponding autoantibodies in 888 samples of verification and validation cohorts. The verification cohort was used to verify the autoantibodies. Samples in the validation cohort were randomly divided into a train set and a test set with the ratio of 6:4. A diagnostic model was established by support vector machines within the train set. The test set further verified the model.

• Link: https://onlinelibrary.wiley.com/doi/10.1111/cas.15217

Mitochondrial mass imbalance is one of the key causes of cardiovascular dysfunction after hypoxia. The activation of dynamin-related protein 1 (Drp1), as well as its mitochondrial translocation, play important roles in the changes of both mitochondrial morphology and mitochondrial functions after hypoxia. However, in addition to mediating mitochondrial fission, whether Drp1 has other regulatory roles in mitochondrial homeostasis after mitochondrial translocation is unknown. In this study, we performed a series of interaction and colocalization assays and found that, after mitochondrial translocation, Drp1 may promote the excessive opening of the mitochondrial permeability transition pore (mPTP) after hypoxia.

• Link: https://www.nature.com/articles/s41419-021-04343-x

HuProt Review: Technical variation, or variation from non-biological sources, is present in most laboratory assays. Correcting for this variation enables analysts to extract a biological signal that informs questions of interest. However, each assay has different sources and levels of technical variation, and the choice of correction methods can impact downstream analyses. Compared to similar assays such as DNA microarrays, relatively few methods have been developed and evaluated for protein microarrays, a versatile tool for measuring levels of various proteins in serum samples.

• Link: https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/pmic.202100033

HuProt Review: Circulating autoantibodies against tumor-associated autoantigens (TAA) may serve as valuable biomarkers for a wide range of diagnostic purposes. Modern immunology offers a large variety of methods for in-depth comparative analysis of the repertoires of circulating antibodies’ antigenic specificities in health and disease. Nevertheless, this research field so far has met somewhat limited clinical success, while numerous data on the repertoires of circulating autoantibodies’ specificities in cancer patients are poorly integrated into the contemporary picture of the immunological and molecular landscapes of human tumors.

• Link: https://link.springer.com/article/10.1134/S0006297921100060