Redefining serological diagnostics with immunoaffinity proteomics

• Published in: Clinical proteomics Vol. 20; no. 1; pp. 1 - 42
• Main Authors: Walter, Jonathan, Eludin, Zicki, Drabovich, Andrei P
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 12-10-2023; BioMed Central
• Subjects: Anemia; Antigens; Autoimmune diseases; Blood transfusions; Celiac disease; Cell-mediated immunity; Crohns disease; Cross-reactivity; Dengue fever; Disease transmission; Immune status; Immunoassay; Immunoassays; Immunoglobulins; Infection; Infections; Infectious diseases; Inflammatory bowel disease; Influenza; Isotypes; Mass spectrometry; Mass spectroscopy; Medical prognosis; Pandemics; Parasitic diseases; Proteins; Proteomics; Quality of life; Review; Rheumatoid arthritis; Scientific imaging; Serological tests; Syphilis; Tropical diseases; Viruses; Massachusetts
• ISSN: 1542-6416; 1559-0275
• DOI: 10.1186/s12014-023-09431-y

Serological diagnostics is generally defined as the detection of specific human immunoglobulins developed against viral, bacterial, or parasitic diseases. Serological tests facilitate the detection of past infections, evaluate immune status, and provide prognostic information. Serological assays were traditionally implemented as indirect immunoassays, and their design has not changed for decades. The advantages of straightforward setup and manufacturing, analytical sensitivity and specificity, affordability, and high-throughput measurements were accompanied by limitations such as semi-quantitative measurements, lack of universal reference standards, potential cross-reactivity, and challenges with multiplexing the complete panel of human immunoglobulin isotypes and subclasses. Redesign of conventional serological tests to include multiplex quantification of immunoglobulin isotypes and subclasses, utilize universal reference standards, and minimize cross-reactivity and non-specific binding will facilitate the development of assays with higher diagnostic specificity. Improved serological assays with higher diagnostic specificity will enable screenings of asymptomatic populations and may provide earlier detection of infectious diseases, autoimmune disorders, and cancer. In this review, we present the major clinical needs for serological diagnostics, overview conventional immunoassay detection techniques, present the emerging immunoassay detection technologies, and discuss in detail the advantages and limitations of mass spectrometry and immunoaffinity proteomics for serological diagnostics. Finally, we explore the design of novel immunoaffinity-proteomic assays to evaluate cell-mediated immunity and advance the sequencing of clinically relevant immunoglobulins.