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Clin Chim Acta. 2019 Dec;499:70-74. doi: 10.1016/j.cca.2019.08.034. Epub 2019 Aug 31.

The presence of S-sulfonated transthyretin in commercial human serum albumin solutions: Potential contribution to neuropathy.

Author information

1
Swedish Medical Center, Englewood, CO, United States of America; Rocky Vista University, Parker, CO, United States of America; St. Anthony Hospital, Lakewood, CO, United States of America; Medical City Plano, Plano, TX, United States of America; Penrose Hospital, Colorado Springs, CO, United States of America; Research Medical Center, Kansas City, MO, United States of America.
2
Swedish Medical Center, Englewood, CO, United States of America; Rocky Vista University, Parker, CO, United States of America.
3
Rocky Vista University, Parker, CO, United States of America; St. Anthony Hospital, Lakewood, CO, United States of America.
4
St. Anthony Hospital, Lakewood, CO, United States of America.
5
Medical City Plano, Plano, TX, United States of America.
6
Penrose Hospital, Colorado Springs, CO, United States of America.
7
Research Medical Center, Kansas City, MO, United States of America.
8
Wesley Medical Center, Wichita, KS, United States of America.
9
Swedish Medical Center, Englewood, CO, United States of America; Rocky Vista University, Parker, CO, United States of America; St. Anthony Hospital, Lakewood, CO, United States of America; Medical City Plano, Plano, TX, United States of America; Penrose Hospital, Colorado Springs, CO, United States of America; Research Medical Center, Kansas City, MO, United States of America; Wesley Medical Center, Wichita, KS, United States of America. Electronic address: davidbme49@gmail.com.

Abstract

BACKGROUND:

Commercial solutions of human serum albumin (HSA) are administered to critically ill patients for the treatment of shock, restoration of blood volume, and the acute management of burns. Previously, conflicting results on the effects of HSA administration have been reported varying from a favorable increase in total plasma antioxidant capacity to a higher mortality rate in traumatic brain injury (TBI) patients. These results could be partially explained due to the known heterogeneity of HSA solutions. We report the discovery of S-sulfonated human transthyretin (hTTR) in HSA solutions.

METHODS:

Proteomics was performed on commercially available solutions of 5% HSA by LC-MS analysis. The MS charge envelope for hTTR was deconvolved to the uncharged native hTTR parent mass (13,762 Da). The parent mass was then integrated, and relative proportions of the 2 major species of hTTR, native and S-sulfonated hTTR (13,842 Da), were calculated.

RESULTS:

The majority of hTTR found in 5% commercial HSA solutions is in the S-sulfonated form regardless of the age of the HSA solution. S-sulfonation of hTTR at the free cysteine residue in position 10 appears to be the result of a mixed disulfide exchange possibly with S-cysteinylated hTTR or S-cysteinylated HSA. hTTR is a tetramer composed of four identical monomers each containing a reduced cysteine residue in position 10. S-sulfonation of hTTR at this cysteine residue can destabilize the hTTR tetramer, an important step in the formation of TTR-related amyloid fibrils.

CONCLUSIONS:

Administration of a commercial HSA solution that already contains S-sulfonated hTTR could potentially contribute to the development of amyloid-related/polyneuropathy in the critically ill.

KEYWORDS:

Albumin; Amyloidosis; Neuropathy; Proteomics; Transthyretin

PMID:
31479652
DOI:
10.1016/j.cca.2019.08.034

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