Mechanisms of Fibril Formation and Cellular Response
Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin in XIth International Symposium on Amyloidosis, 2007
AA amyloidosis is a renowned complication of chronic inflammatory states, characterized by the extracellular deposition of insoluble protein fibrils in tissues, ultimately resulting in organ dysfunction (1). Familial Mediterranean fever (FMF), the most prevalent of the hereditary periodic fevers, is the most frequently reported cause of AA amyloidosis in the Mediterranean basin (2) and remains the most ominous complication of this inflammatory disorder (3). Quantification of amyloid A protein by enzyme-linked immunosorbent assay (ELISA) has been developed in recent years as an alternative method to traditional Congo red staining in the detection of amyloid deposits in fat tissue (4). Among the reputed advantages of this immunochemical method is the ability to quantitatively monitor tissue amyloid at different time points. The aim of the present study was to establish the relationship of serial quantitative amyloid A measurements in fat tissue of FMF patients with amyloidosis with their clinical course, over a two year period.
Practice Paper 8: Answers
Anthony B. Starr, Hiruni Jayasena, David Capewell, Saran Shantikumar in Get ahead! Medicine, 2016
In amyloidosis, there is deposition of extracellular fibrillar proteins in tissues and organs. The two main types of amyloidosis are amyloid light chain (AL) and amyloid A (AA). AL amyloidosis, also incorrectly referred to as primary amyloidosis, is due to the clonal proliferation of plasma cells and particularly affects the cardiovascular system. AA amyloidosis, also known as reactive systemic amyloidosis, is due to the production and deposition of amyloid in chronic inflammatory conditions such as Crohn’s disease, RA and TB. In AA amyloidosis, amyloid A protein is deposited in the kidneys, liver and spleen, causing renal failure and hepatosplenomegaly. Cardiovascular involvement is rare. The renal complications of amyloidosis include proteinuria, nephrotic syndrome and end-stage renal failure. Amyloidosis is traditionally diagnosed based on a biopsy of the affected tissue. The fibrillar protein shows green birefringence when stained with Congo red and examined beneath a polarized light. AL amyloidosis can be managed with chemotherapy or stem cell transplantation, but is usually fatal within 2 years. AA amyloidosis may respond to treatment of the underlying cause.
The Noncollagenous Proteins of the Intervertebral Disc *
Peter Ghosh in The Biology of the Intervertebral Disc, 2019
The prognosis of reactive AA amyloidosis is more favorable than for idiopathic or myeloma associated amyloidosis. The reported survival rates are about 2 years236 for the former and 4 months for the latter.237 Amyloidosis has been estimated to be the cause of 43 to 47% of deaths among European patients with JRA,238 while the lower incidence of this condition in the U.S. reflects the lower death rate there from JRA.215 The proportion of deaths caused by amyloidosis in adult onset rheumatoid arthritis is variable, but generally much lower than for JRA. Koota et al.239 reported that amyloidosis was the cause of deaths in 8% of rheumatoid arthritis patients examined at autopsy.
Causes of AA amyloidosis: a systematic review
Published in Amyloid, 2020
Anne Floor Brunger, Hans L. A. Nienhuis, Johan Bijzet, Bouke P. C. Hazenberg
Hundred and fifty diseases were initially reported to be associated with the development of AA amyloidosis. Ninety-four of the 795 publications presented information concerning more than one disease. Electron microscopy was described in 107 publications (13% of all). Congo red-stained tissue was described in 560 (70%) publications of which birefringence was described in 310 (55%), the potassium permanganate test in 140 (25%), and anti-AA immunohistochemistry in 310 (55%). Amyloid A was proven in 207 (26% of all) publications of which 140 (68%) were strongly associated with an underlying disease process. The quality of the immunohistochemistry was seldom checked by using a positive and negative control and criteria of the underlying inflammatory disease were not described consistently among the various diseases.
Multiple nodular pulmonary amyloidosis in a patient with rheumatoid arthritis
Published in Modern Rheumatology Case Reports, 2019
Michiko Morishita, Tomoko Kawabata, Keiji Ohashi, Yoshia Miyawaki, Haruki Watanabe, Ken-Ei Sada, Jun Wada
Amyloidosis is a rare disorder in which fibrillary proteins called “amyloids” are deposited in the extracellular spaces of organs and tissue [1]. Systemic amyloid A (AA) amyloidosis occurs due to the tissue deposition of serum AA (SAA). AA amyloidosis is known to occur in chronic inflammatory conditions of connective tissue diseases, such as rheumatoid arthritis (RA). The prevalence in systemic amyloidosis patients with RA ranges from 7% to 26% [2,3]. AA amyloidosis most commonly occurs in the kidneys and the gastrointestinal tracts and rarely occurs in the lungs [4]. A previous report found that pulmonary amyloidosis is much more difficult to diagnose by transbronchial lung biopsy (TBLB) than by open lung biopsy [5]. However, there are few reports on pulmonary amyloidosis diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which is a minimally invasive method with a high diagnostic yield [6]. We herein report a case of RA of multiple nodular pulmonary amyloidosis that was diagnosed by EBUS-TBNA.
AA amyloidosis – Benefits and prospects of IL-6 inhibitors
Published in Modern Rheumatology, 2019
Among the complications of chronic inflammatory diseases, amyloid A (AA) amyloidosis is one of the most severe because of its poor prognosis. AA amyloidosis commonly affects the kidneys and gastrointestinal tract, and is characterized by various clinical symptoms, such as progressive proteinuria as well as renal dysfunction and failure. Control of the underlying disease, i.e. the suppression of serum amyloid A (SAA) levels, is the most critical step in the treatment of AA amyloidosis. Immunosuppressants, such as methotrexate, azathioprine, cyclophosphamide, and moderate doses of prednisolone, have previously been used to accomplish this. However, the satisfactory suppression of SAA levels cannot be achieved in some active cases, and the functions of the affected organs deteriorate. The prognosis of patients in the advanced stages of AA amyloidosis is generally poor. The major causes of death are renal failure and infection. Some retrospective studies and case reports demonstrated that anti-tumor necrosis factor (TNF) therapies were useful against AA amyloidosis [1–5]. Although treatments with anti-TNF agents reduce acute-phase reactants, such as C-reactive protein (CRP) and SAA, in chronic inflammatory diseases, the complete normalization of these acute-phase proteins is low [5].
Related Knowledge Centers
- Amyloidosis
- Ankylosing Spondylitis
- Chronic Kidney Disease
- Inflammation
- Kidney Failure
- Serum Amyloid A
- Autoimmune Disease
- Acute-Phase Protein
- Kidney Dialysis
- Rheumatoid Arthritis