Biomarkers that show high sensitivity and specificity are needed for the early diagnosis and prognosis of cancer. An immune response to cancer is elicited in humans, as demonstrated, in part, by the identification of autoantibodies against a number of tumor-associated antigen (TAAs) in sera from patients with different types of cancer. Identification of TAAs and their cognate autoantibodies is a promising strategy for the discovery of relevant biomarkers. During the past few years, three proteomic approaches, including serological identification of antigens by recombinant expression cloning (SEREX), serological proteome analysis (SERPA) and, more recently, protein microarrays, have been the dominant strategies used to identify TAAs and their cognate autoantibodies. In this review, we aim to describe the advantages, drawbacks and recent improvements of these approaches for the study of humoral responses. Finally, we discuss the definition of autoantibody signatures to improve sensitivity for the development of clinically relevant tests.
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http://dx.doi.org/10.1586/epr.09.56 | DOI Listing |
J Exp Med
February 2025
Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.
IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.
View Article and Find Full Text PDFArthritis Rheumatol
January 2025
Department of Medicine, Mayo Clinic Alix School of Medicine, Rochester, MN, 55905, USA.
Rheumatoid arthritis (RA) is a life-long autoimmune disease caused by the confluence of genetic and environmental variables that lead to loss of self-tolerance and persistent joint inflammation. RA occurs at the highest incidence in individuals >65 years old, implicating the aging process in disease susceptibility. Transformative approaches in molecular immunology and in functional genomics have paved the way for pathway paradigms underlying the replacement of immune homeostasis with auto-destructive immunity in affected patients, including the process of immune aging.
View Article and Find Full Text PDFSci Rep
January 2025
Discovery3 Team, Department of Research and Early Development, GC Biopharma, 93, Ihyeon-ro 30Beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do, South Korea.
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening blood disorder characterized by the formation of blood clots in small blood vessels. It is caused by antibodies targeting the A disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13), which plays a role in cleaving von Willebrand factor. Most patients with iTTP have autoantibodies against specific domains of the ADAMTS13 protein, particularly the cysteine-rich and spacer domains.
View Article and Find Full Text PDFSci Immunol
January 2025
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Human recombination-activating gene (RAG) deficiency can manifest with distinct clinical and immunological phenotypes. By applying a multiomics approach to a large group of -mutated patients, we aimed at characterizing the immunopathology associated with each phenotype. Although defective T and B cell development is common to all phenotypes, patients with hypomorphic variants can generate T and B cells with signatures of immune dysregulation and produce autoantibodies to a broad range of self-antigens, including type I interferons.
View Article and Find Full Text PDFBlood Adv
January 2025
KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
Allosteric regulation of ADAMTS13 (A Disintegrin And Metalloproteinase with ThromboSpondin type-1 motif, member 13) activity involves an interaction between its Spacer (S) and CUB1-2 domains to keep the enzyme in a closed, latent conformation. Monoclonal antibodies (mAb) uncouple the S-CUB interaction to open the ADAMTS13 conformation and thereby disrupt the global enzyme latency. The molecular mechanism behind this mAb-induced allostery remains poorly understood.
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