Insight into the Protein Composition of Immunoglobulin Light Chain Deposits of Eyelid, Orbital and Conjunctival Amyloidosis

Abstract

Amyloidosis is a disease characterized by the formation of extracellular amyloid deposits. Immunoglobulin light-chain amyloidosis can appear as a local disorder presenting with mild symptoms or as a life threatening systemic disease. The systemic form of immunoglobulin light-chain amyloidosis is the most common type of amyloidosis in western countries although it is a rare disease. Identification of the proteins forming amyloid fibrils is essential for the diagnosis of the disease and knowledge about the overall protein composition of the deposits may lead to a larger understanding of the deposition events thereby facilitating a more detailed picture of the molecular pathology. In this pilot study, we investigated the protein composition of amyloid deposits isolated from human specimens of the eyelid, conjunctiva, and orbit. Deposits and internal control tissue (patient tissue without apparent deposits) were procured by laser capture microdissection. Proteins in the captured amyloid and control samples were quantified by liquid chromatography tandem mass spectrometry using the label-free exponential modified Protein Abundance Index (emPAI) method. Immunoglobulin light chain kappa or lambda was found to be the most predominant protein in the amyloid deposits from the eyelid, conjunctiva, and orbit. Five proteins, apolipoprotein A-I, carboxypeptidase B2 (TAFI), complement component C9, fibulin-1 and plasminogen were found solely across all amyloid but not in the control tissue. In addition, the protein profiles identified apolipoprotein E and serum amyloid P component to be associated with the immunoglobulin light chain deposits across all three tissues analyzed. The method used in this study provided high sensitivity and specificity for the type of amyloid and may provide additional information on the pathology of the amyloid deposits in the ocular tissues studied.

PTM-Shepherd: Analysis and Summarization of Post-Translational and Chemical Modifications From Open Search Results

“…( 16 ) for their study. Two of these data sets, titled “Nielsen” (PXD000743) and “Buthelezi” (PXD013107), were acquired on SCIEX TripleTOFs ( 17 ). The Nielsen data set was acquired on a TripleTOF 5600+ and consists of 218,449 scans across 20 SCIEX.wiff files, and the Buthelezi data set was acquired on a TripleTOF 6600 and consists of 474,726 scans across 12 SCIEX.wiff files.…”

The serine protease HtrA1 cleaves misfolded transforming growth factor β–induced protein (TGFBIp) and induces amyloid formation

“…HtrA1 is expressed in the healthy cornea (1), and although its activation mechanism (18) and exact role are unclear, the homology to its bacterial counterpart, DegP, suggests that HtrA1 is involved in protein quality control (19, 20). HtrA1 is associated with amyloid deposits of immunoglobulin light chain amyloidosis (21), drusen deposits in age-related macular degeneration (22), and Alzheimer's disease (23). Concerning Alzheimer's disease, HtrA1 likely plays a role in amyloid protein turnover because the protease can degrade both monomeric and aggregated versions of several amyloid proteins (23, 24) and leads to the disintegration of amyloid fibrils (17).…”

Light chain amyloidosis of the lacrimal glands in a patient with chronic dacryoadenitis

“…A protein amyloid (AA) typically accumulates in patients with chronic inflammatory diseases, while λ and k light chain proteins deposit as a consequence of B-cell dyscrasia or plasma cell clonal expansion. 1,5 In the current case, A protein amyloid may have been expected in the context of chronic lacrimal gland inflammation; however, λ light chains were identified 6 months after a nonspecific biopsy. 7 There are only a small number of similar reports in which the initial biopsy of chronically inflamed tissue demonstrated nonspecific or normal tissue with subsequent identification of AL amyloid at repeat biopsy.…”

“…Amyloidosis encompasses a spectrum of organ dysfunction disorders caused by the extracellular deposition of abnormally folded proteins. 1 Over 30 precursor proteins have been identified, all displaying pathognomonic Congo red staining, which demonstrates apple green dichroism and birefringence with polarized light. 1,2 Disease is classified according to the amyloid fibril protein and number of accumulation sites.…”

“…1 Over 30 precursor proteins have been identified, all displaying pathognomonic Congo red staining, which demonstrates apple green dichroism and birefringence with polarized light. 1,2 Disease is classified according to the amyloid fibril protein and number of accumulation sites. 3 Systemic light chain (AL) amyloidosis is the most common subtype of disease and frequently affects the heart, kidneys, liver, and peripheral nerves.…”