Detection and identification of protein variants and adducts in blood and tissues: an application of soft ionization mass spectrometry to clinical diagnosis
| Autor: | Toyofumi Nakanishi, Akira Shimizu, Masahiko Kishikawa, Ayako Miyazaki |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Immunoprecipitation
Clinical Biochemistry Mass spectrometry Biochemistry High-performance liquid chromatography Mass Spectrometry Analytical Chemistry Hemoglobins Diagnosis medicine Humans Prealbumin Amino Acid Sequence chemistry.chemical_classification Chromatography biology Superoxide Dismutase Cell Biology General Medicine medicine.disease Transthyretin Blood chemistry biology.protein Hemoglobin Target protein Glycoprotein Polyneuropathy Chromatography Liquid |
| Zdroj: | Journal of Chromatography B. 776:15-30 |
| ISSN: | 1570-0232 |
| DOI: | 10.1016/s1570-0232(02)00031-4 |
| Popis: | The detection and identification of protein variants and abnormally increased modified proteins are important for clinical diagnosis. We applied soft ionization mass spectrometry (MS) to analyze proteins in blood and tissues from various patients. Over the past 8 years, we diagnosed 132 cases (55 kinds) of variant proteins including hemoglobin (Hb), transthyretin (TTR), and Cu/Zn-superoxide dismutase (SOD-1), using MS as the leading technology. Of these variants, eight were new, and nine were the first cases in Japan. Some abnormal Hb cause diseases, and most of them cause erroneous levels of glycated Hb, HbA1c, i.e., a popular index of diabetes. Most of the variant TTR causes amyloidotic polyneuropathy. Variant SOD-1 causes amyotrophic lateral sclerosis. We first showed that immunoprecipitation by a specific antiserum is a reliable and simple method to prepare protein from sera and tissues for analysis by matrix-assisted laser desorption time-of-flight MS, and liquid chromatography–electrospray ionization MS (LC–ESI-MS). The use of this technology has become widespread. Using an immunoprecipitated target protein and LC–ESI-MS, we showed that the ratios of tetra-, di- and a-sialo-transferrin from two cases of congenital glycoprotein deficient syndrome were clearly distinguishable from those of control samples. We first reported a unique modified form of TTR, that is, S-sulfonated TTR, which increased markedly and specifically in three cases with molibdenum cofactor deficiency. We proposed that S-sulfonated TTR is a useful marker for screening this disease. ESI-MS was successfully used for the accurate determination of HbA1c, and we clarified the extent of discrepancies between the HbA1c value measured by conventional methods and the accurate values for samples containing various Hb variants determined by the MS method. |
| Databáze: | OpenAIRE |
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