Jean D. Sipe

Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature Committee of the International Society of Amyloidosis

The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XIIIth International Symposium, May 6–10, 2012, Groningen, The Netherlands, to formulate recommendations on amyloid fibril protein nomenclature and to consider newly identified candidate amyloid fibril proteins for inclusion in the ISA Amyloid Fibril Protein Nomenclature List. The need to promote utilization of consistent and up to date terminology for both fibril chemistry and clinical classification of the resultant disease syndrome was emphasized. Amyloid fibril nomenclature is based on the chemical identity of the amyloid fibril forming protein; clinical classification of the amyloidosis should be as well. Although the importance of fibril chemistry to the disease process has been recognized for more than 40 years, to this day the literature contains clinical and histochemical designations that were used when the chemical diversity of amyloid diseases was poorly understood. Thus, the continued use of disease classifications such as familial amyloid neuropathy and familial amyloid cardiomyopathy generates confusion. An amyloid fibril protein is defined as follows: the protein must occur in body tissue deposits and exhibit both affinity for Congo red and green birefringence when Congo red stained deposits are viewed by polarization microscopy. Furthermore, the chemical identity of the protein must have been unambiguously characterized by protein sequence analysis when so is practically possible. Thus, in nearly all cases, it is insufficient to demonstrate mutation in the gene of a candidate amyloid protein; the protein itself must be identified as an amyloid fibril protein. Current ISA Amyloid Fibril Protein Nomenclature Lists of 30 human and 10 animal fibril proteins are provided together with a list of inclusion bodies that, although intracellular, exhibit some or all of the properties of the mainly extracellular amyloid fibrils.

PTX3, A Prototypical Long Pentraxin, Is an Early Indicator of Acute Myocardial Infarction in Humans

BACKGROUND Inflammation is an important component of ischemic heart disease. PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is altered in patients with acute myocardial infarction (AMI) has not yet been tested. METHODS AND RESULTS Blood samples were collected from 37 patients admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to normal in all but 3 patients at hospital discharge and were unrelated to AMI site or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C-reactive protein peaked in plasma at 24 hours after CCU admission, much later than PTX3 (P<0.001). Patients >64 years old and women had significantly higher PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS PTX3 is present in the intact myocardium, increases in the blood of patients with AMI, and disappears from damaged myocytes. We suggest that PTX3 is an early indicator of myocyte irreversible injury in ischemic cardiomyopathy.

Analytical evaluation of particle-enhanced immunonephelometric assays for C-reactive protein, serum amyloid A and mannose-binding protein in human serum.

Against a background of growing interest in more sensitive assays for quantifying various acute phase proteins, we evaluated the performance of recently developed tests for C-reactive protein (CRP), serum amyloid A (SAA) and mannose-binding protein (MBP) on the Behring nephelometer II (BN II). Sample results outside the calibration ranges of 3·5 to 220 mg/L for CRP, 3·3 to 215 mg/L for SAA and 0·09 to 5·6 mg/L for MBP were automatically re-measured at another dilution. The lower limits of detection were 0·01, 0·7 and 0·01 mg/L for CRP, SAA and MBP, respectively. The coefficients of variation (CV) for intra- (n ⩾ 20) and inter- (n ⩾ 15) assay precision were < 5·2% and < 8·5%, respectively, for the three proteins at concentrations representing low, normal and high. Linearity for each method was within 5% of the expected values throughout the calibration range. We observed no significant interference from bilirubin (up to 300 mg/L) or haemoglobin (up to 10 g/L) for the three tests. Method comparison studies performed for CRP and SAA yielded the following results: y (CRP on BN II) = 0·75x (ELISA, Hemagen) −0·25 mg/L (r = 0·981, Sy/x = 2·1 mg/L; y (SAA on BN II) = 1·44x (ELISA, Hemagen) −9·9 mg/L (r = 0·972, Sy/x = 6·9 mg/L), where ELISA is enzyme-linked immunosorbent assay. Reference intervals established in 261 adult blood donors (aged 36·2 ± 9·0 years) were found to be log-normal with 2·5th, 50th and 97·5th centiles of < 0·17, 100 and 10·1 mg/L for CRP, < 0·84, 2·10 and 9·70 mg/L for SAA; and 0·30, 1·28 and 4·10 mg/L for MBP. We observed no relationship with CRP concentration and age; however, SAA levels increased with age while MBP levels decreased. The BN II provides a simple, rapid and sensitive system for measuring CRP, SAA and MBP in human serum.

A primer of amyloid nomenclature

The increasing knowledge of the exact biochemical nature of the localized and systemic amyloid disorders has made a logical and easily understood nomenclature absolutely necessary. Such a nomenclature, biochemically based, has been used for several years but the current literature is still mixed up with many clinical and histochemically based designations from the time when amyloid in general was poorly understood. All amyloid types are today preferably named by their major fibril protein. This makes a simple and rational nomenclature for the increasing number of amyloid disorders known in humans and animals.

Amyloid: Toward terminology clarification Report from the Nomenclature Committee of the International Society of Amyloidosis

The modern nomenclature of amyloidosis now includes 25 human and 8 animal fibril proteins. To be included in the list, the protein has to be a major fibril protein in extracellular deposits, which have the characteristics of amyloid, including affinity for Congo red with resulting green birefringence. Synthetic fibrils with amyloid properties are best named ‘amyloid-like’. With increasing knowledge, however, the borders between different protein aggregates tend to become less sharp.

Nomenclature 2014: Amyloid fibril proteins and clinical classification of the amyloidosis

The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XIVth Symposium of the Society, April 27–May 1, 2014, Indianapolis, IN, to assess and formulate recommend...

The role of macrophages in the acute-phase response: SAA inducer is closely related to lymphocyte activating factor and endogenous pyrogen

Abstract An increase in the concentration of the acute-phase reactant, serum amyloid A (SAA), following endotoxin treatment, is a consequence of the action of lipopolysaccharide (LPS) on macrophages to produce a monokine, the SAA inducer, which in turn, triggers SAA synthesis by hepatocytes. We have found that murine SAA inducer is closely related, if not identical, to murine lymphocyte activating factor (LAF), otherwise known as Interleukin 1 (IL 1). Furthermore, both rabbit endogenous pryrogen (EP), which is believed to be identical to LAF (IL 1), and human LAF (IL 1), induced elevated SAA concentrations in C3H/HeJ mice. Antiserum previously shown to block both pyrogenic and thymocyte proliferating activities of the species of rabbit EP exhibiting an isoelectric point of pH 7.3 (EP 7), also blocked the SAA inducing activity of EP7. Phenylglyoxal treatment of highly purified murine LAF (IL 1) abrogated both thymocyte proliferating activity and the SAA inducing activity. These studies support and extend previous reports suggesting that within 2 hr of an inflammatory stimulus, macrophages produce a monokine that acts systemically to alter body temperature, activate T cells, and induce hepatic protein synthesis of acute-phase reactants.

Tissue Engineering and Reparative Medicine

Abstract: Reparative medicine is a critical frontier in biomedical and clinical research. The National Institutes of Health Bioengineering Consortium (BECON) convened a symposium titled “Reparative Medicine: Growing Tissues and Organs,” which was held on June 25 and 26, 2001 in Bethesda, Maryland. The relevant realms of cells, molecular signaling, extracellular matrix, engineering design principles, vascular assembly, bioreactors, storage and translation, and host remodeling and the immune response that are essential to tissue engineering were discussed. This overview of the scientific program summarizes the plenary talks, extended poster presentations and breakout session reports with an emphasis on scientific and technical hurdles that must be overcome to achieve the promise of restoring, replacing, or enhancing tissue and organ function that tissue engineering offers.

Changes in Human Serum Amyloid A and C-Reactive Protein after Etiocholanolone-Induced Inflammation

Secondary amyloidosis is a complication of diseases characterized by recurrent acute inflammation. In this study, a standardized stimulus which induced fever and inflammation was given to six normal subjects (19-24 yr old) to follow the fluctuation in concentration of serum amyloid A (SAA), the precursor of the secondary amyloid fibril protein. After a single intramuscular injection of etiocholanolone (0.3 mg/kg), blood samples were drawn twice a day for 12 days for determination of SAA by solid phase radioimmunoassay. From a base line of <100 mug/ml, the SAA concentration began rising within 12 h to a maximum value at about 48 h of 1,350-1,800 mug/ml in three males and 380-900 mug/ml in three females and returned to base line by 4-5 days. The SAA response showed a similar time response to C-reactive protein (CRP), a well-documented acute phase protein which was assayed semiquantitatively by capillary tube precipitin reaction. CRP, but not SAA, showed a quantitative correlation with the amount of fever induced by etiocholanolone. One subject exhibited a second rise in SAA and CRP concentrations after acute over-indulgence with alcohol, suggesting that acute liver damage may have caused an acute phase reaction. Thus, a controlled episode of fever and inflammation produced a prompt and prolonged elevation of SAA and CRP concentrations. Unlike SAA, CRP has not been implicated in the pathogenesis of amyloidosis, although its relationship to the P component of amyloid has recently been established.

Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines

Abstract The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XVth Symposium of the Society, 3 July–7 July 2016, Uppsala, Sweden, to assess and formulate recommendations for nomenclature for amyloid fibril proteins and the clinical classification of the amyloidoses. An amyloid fibril must exhibit affinity for Congo red and with green, yellow or orange birefringence when the Congo red-stained deposits are viewed with polarized light. While congophilia and birefringence remain the gold standard for demonstration of amyloid deposits, new staining and imaging techniques are proving useful. To be included in the nomenclature list, in addition to congophilia and birefringence, the chemical identity of the protein must be unambiguously characterized by protein sequence analysis when possible. In general, it is insufficient to identify a mutation in the gene of a candidate amyloid protein without confirming the variant changes in the amyloid fibril protein. Each distinct form of amyloidosis is uniquely characterized by the chemical identity of the amyloid fibril protein that deposits in the extracellular spaces of tissues and organs and gives rise to the disease syndrome. The fibril proteins are designated as protein A followed by a suffix that is an abbreviation of the parent or precursor protein name. To date, there are 36 known extracellular fibril proteins in humans, 2 of which are iatrogenic in nature and 9 of which have also been identified in animals. Two newly recognized fibril proteins, AApoCII derived from apolipoprotein CII and AApoCIII derived from apolipoprotein CIII, have been added. AApoCII amyloidosis and AApoCIII amyloidosis are hereditary systemic amyloidoses. Intracellular protein inclusions displaying some of the properties of amyloid, “intracellular amyloid” have been reported. Two proteins which were previously characterized as intracellular inclusions, tau and α-synuclein, are now recognized to form extracellular deposits upon cell death and thus have been included in Table 1 as ATau and AαSyn.