Systemic AA Amyloidosis in Captive Cheetahs (Acinonyx jubatus)

Ongoing disease surveillance of necropsied captive cheetahs ( Acinonyx jubatus) ( n = 141) revealed a high prevalence of renal amyloidosis ( n = 54 [38%]; age 1 to 16 years). The prevalence increased from 20% in pre-1990 necropsies to 70% of cheetahs necropsied in 1995. In 74% of the cheetahs with amyloidosis, renal failure was determined to be the sole or partial cause of death. Papillary necrosis was seen only in affected cheetahs and involved 25% of these animals. Amyloid was present predominantly in the medullary interstitium, with minimal glomerular involvement. The amyloid deposits were immunohistochemically identified as AA type using antisera to both human and canine protein AA. A high percentage (52%) of animals with renal amyloid also had subsinusoidal hepatic AA amyloid deposits. Inflammatory diseases were identified in 100% of affected cheetahs. The most common inflammatory disease was chronic lymphoplasmacytic gastritis. The prevalence and severity of gastritis was higher in cheetahs with amyloidosis, and the prevalence of severe gastritis increased from 16% to 43%, coinciding with the increase in prevalence of amyloidosis. These findings suggest that cheetahs have a high prevalence of systemic amyloidosis in response to inflammation and that renal amyloidosis is an increasingly significant cause of morbidity and mortality in captive cheetah populations. Factors of potential importance in the apparent high prevalence of AA amyloidosis in cheetahs are currently being investigated in our laboratories.

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Rituximab Therapy in Renal Amyloidosis Secondary to Rheumatoid Arthritis

Biomolecules ◽

10.3390/biom8040136 ◽

2018 ◽

Vol 8 (4) ◽

pp. 136 ◽

Cited By ~ 3

Author(s):

Levent Kilic ◽

Abdulsamet Erden ◽

Yusuf Sener ◽

Berkan Armagan ◽

Alper Sari ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Improvement ◽

Inflammatory Diseases ◽

Case Series ◽

New Drugs ◽

Renal Amyloidosis ◽

Secondary Amyloidosis ◽

Aa Amyloidosis ◽

Amyloid A ◽

Significant Clinical Improvement

Secondary amyloid A (AA) amyloidosis is a late and serious complication of poorly controlled, chronic inflammatory diseases. Rheumatoid arthritis (RA) patients with poorly controlled, longstanding disease and those with extra-articular manifestations are under risk for the development of AA amyloidosis. Although new drugs have proven to be significantly effective in the treatment of secondary AA amyloidosis, no treatment modality has proven to be ideal. To date, only in small case series preliminary clinical improvement have been shown with rituximab therapy for AA amyloidosis secondary to RA that is refractory to TNF-α inhibitors (TNF-i) therapy. In these case series, we assessed the efficacy and safety of rituximab therapy for patients with RA and secondary amyloidosis. Hacettepe University Biologic Registry was developed at 2005. The data of the RA patients who were prescribed a biological drug were recorded regularly. Patients with biopsy proven AA amyloidosis patients were screened. Of 1022 RA patients under biologic therapy, 0.7% patients had clinically apparent histologically confirmed amyloidosis. Four of seven patients who were prescribed rituximab at least one infusion enrolled to those case series. Two of four patients showed significant clinical improvement and one of them also had decrease in proteinuria and the other one had stable renal function and proteinuria. The main goal for the treatment of AA amyloidosis is to control the activity of the underlying disorder. In this study, we showed that rituximab may be an effective treatment in RA patients with amyloidosis who were unresponsive to conventional disease modifying anti-rheumatic drugs (DMARDs) and/or TNFi.

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AA-amyloidosis in captive northern tree shrews (Tupaia belangeri)

Veterinary Pathology ◽

10.1177/03009858211066847 ◽

2021 ◽

pp. 030098582110668

Author(s):

Annette Klein ◽

Ute Radespiel ◽

Felix Felmy ◽

Tina Brezina ◽

Malgorzata Ciurkiewicz ◽

...

Keyword(s):

Renal Medulla ◽

Aa Amyloidosis ◽

Laboratory Findings ◽

Tree Shrews ◽

Tupaia Belangeri ◽

Amyloid Deposits ◽

High Prevalence ◽

Inflammatory Processes ◽

Congo Red Staining ◽

Important Disease

A high prevalence of AA-amyloidosis was identified in a breeding colony of northern tree shrews ( Tupaia belangeri) in a retrospective analysis, with amyloid deposits in different organs being found in 26/36 individuals (72%). Amyloid deposits, confirmed by Congo red staining, were detected in kidneys, intestines, skin, and lymph nodes, characteristic of systemic amyloidosis. Immunohistochemically, the deposited amyloid was intensely positive with anti-AA-antibody (clone mc4), suggesting AA-amyloidosis. The kidneys were predominantly affected (80%), where amyloid deposits ranged from mild to severe and was predominantly located in the renal medulla. In addition, many kidneys contained numerous cysts with atrophy of the renal parenchyma. There was no significant association between concurrent neoplastic or inflammatory processes and amyloidosis. The lack of distinctive predisposing factors suggests a general susceptibility of captive T. belangeri to develop amyloidosis. Clinical and laboratory findings of a female individual with pronounced kidney alterations were indicative of renal failure. The observed tissue tropism with pronounced kidney alterations, corresponding renal dysfunction, and an overall high prevalence suggests amyloidosis as an important disease in captive tree shrews.

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Nierenmanifestationen bei Amyloidose und Sarkoidose

DMW - Deutsche Medizinische Wochenschrift ◽

10.1055/s-0043-106565 ◽

2018 ◽

Vol 143 (02) ◽

pp. 101-109

Author(s):

Jörg Beimler ◽

Martin Zeier

Keyword(s):

Interstitial Nephritis ◽

Inflammatory Diseases ◽

Renal Involvement ◽

Plasma Cell Dyscrasia ◽

Renal Amyloidosis ◽

Al Amyloidosis ◽

Renal Lesion ◽

Aa Amyloidosis ◽

Granulomatous Interstitial Nephritis ◽

Chronic Inflammatory Diseases

AbstractAmyloidosis is a rare disease characterized by extracellular deposition of fibrils. Among the most common forms of systemic amyloidosis with renal involvement are AL-amyloidosis based on plasma cell dyscrasia and AA-amyloidosis in chronic inflammatory diseases. Depending on the affected renal compartment, the clinical appearance of renal amyloidosis varies. The pattern of renal amyloid deposition can be glomerular, interstitial, tubular or even vascular. Renal amyloid deposits are detected by renal biopsy. Patients with glomerular deposits typically show severe nephrotic syndrome with volume overload. Patients with predominantly tubulo-interstitial or vascular deposits typically exhibit lower proteinuria and progressive renal impairment. Treatment strategies for renal amyloidosis are primarily based on the treatment of the underlying disease including chemotherapy or stem cell transplantation in AL-amyloidosis or treatment of chronic inflammatory diseases in AA-amyloidosis. Granulomatous interstitial nephritis is the most common renal lesion occurring in sarcoidosis. Therapy of granulomatous interstitial nephritis is mainly based on the use of glucocorticoids.

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Amino acid sequence analysis of amyloid protein A (AA) from cats (captive cheetahs: Acinonyx jubatus) with a high prevalence of AA amyloidosis

Amyloid ◽

10.3109/13506129709014381 ◽

1997 ◽

Vol 4 (3) ◽

pp. 171-177 ◽

Cited By ~ 10

Author(s):

Kenneth H. Johnson ◽

Knut Sletten ◽

Linda Munson ◽

Timothy D. O'brien ◽

Rebecca Papendick ◽

...

Keyword(s):

Amino Acid ◽

Sequence Analysis ◽

Amino Acid Sequence ◽

Protein A ◽

Amyloid Protein ◽

Aa Amyloidosis ◽

Amino Acid Sequence Analysis ◽

Acinonyx Jubatus ◽

High Prevalence

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Is renal amyloidosis uncommon in Egypt? A-25-year study

Journal of Nephropathology ◽

10.15171/jnp.2019.05 ◽

2018 ◽

Vol 8 (1) ◽

pp. 5-5

Author(s):

Amal Labib ◽

Marwa M Shakweer ◽

Manal I Salman ◽

Elham I Seif

Keyword(s):

Inflammatory Diseases ◽

Renal Involvement ◽

Underlying Disease ◽

Renal Amyloidosis ◽

Al Amyloidosis ◽

Positive Staining ◽

Aa Amyloidosis ◽

University Hospitals ◽

Amyloid A ◽

Renal Biopsies

Background: Renal amyloidosis is a well-known disease. The forms of amyloidosis that are frequently associated with renal involvement are AL and AA amyloidosis. In Theodor Bilharz Institute, in Egypt, 2.5% of the total number of renal biopsies examined showed amyloidosis including secondary type in 80% and primary type in 20% of cases. Objectives: To investigate the prevalence of amyloidosis among Egyptian renal patients within 25 years and to screen the amyloid type whether AA or AL. Materials and Methods: Demographic and pathological data of archived renal biopsies presented to Ain Shams University hospitals in 25 years (1990-2015) were the material of this study. The diagnosis of all renal biopsies included in the study was confirmed by electron microscopy (EM). Immunohistochemical (IHC) staining of paraffin blocks for amyloid typing was carried out on archived material from (2010-2015). Results: Of a total number of 3962 biopsies examined; 118 were renal amyloidosis (2.97%). IHC typing of the screened samples revealed positive staining for amyloid A protein in 14 cases (73.68%). Light chain AL amyloidosis was found in 5 cases (26.3%). Conclusions: Renal amyloidosis is not uncommon in Egypt. AA amyloidosis represents the commonest type of renal amyloidosis in this study. The most common underlying disease was systemic inflammatory diseases, on top of familial Mediterranean fever (FMF).

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Deposition, Clearance, and Reinduction of Amyloid A Amyloid in Interleukin 1 Receptor Antagonist Knockout Mice

Veterinary Pathology ◽

10.1177/0300985816658772 ◽

2016 ◽

Vol 54 (1) ◽

pp. 99-110 ◽

Cited By ~ 4

Author(s):

K. Watanabe ◽

K. Uchida ◽

J. K. Chambers ◽

N. Ushio ◽

H. Nakayama

Keyword(s):

Receptor Antagonist ◽

Knockout Mice ◽

Interleukin 1 ◽

Recovery Process ◽

Amyloid Deposition ◽

Aa Amyloidosis ◽

Amyloid A ◽

Enhancing Factor ◽

Amyloid Deposits ◽

Amyloid Enhancing Factor

Amyloid A (AA) amyloidosis is characterized by the extracellular deposition of AA amyloid and results in the irreversible dysfunction of parenchymal organs. In experimental models, AA amyloid deposits are cleared following a decrease in circulating serum amyloid A (SAA) concentrations. Additional inflammatory stimuli during this recovery process may induce more severe amyloid redeposition. In the present study, we confirmed the deposition, clearance, and reinduction of AA amyloid deposits in interleukin 1 receptor antagonist knockout mice (IL-1raKO) and studied the SAA levels and amyloid-enhancing factor activity based on the time-dependent changes of amyloid deposition. Histopathologically, following initial (day 0) injection of amyloid-enhancing factor in combination with an inflammatory stimulus (silver nitrate [AgNO3]), amyloid deposition peaked by day 20, and its deposition gradually decreased after day 35. SAA concentrations in serum were precipitously elevated on day 1 but returned to normal levels by day 10, whereas the SAA dimer was detected in serum after day 45. An additional AgNO3 injection was administered to mice with amyloidosis on day 5, 10, 35, or 50, and all mice developed large amyloid deposits. Amyloid deposition was most severe in mice treated with AgNO3 on day 35. The inoculation of sera from mice with AA amyloidosis, combined with AgNO3, induced AA amyloidosis. Serum samples collected on days 35 and 50, which contained high concentrations of the SAA dimer, induced amyloidosis in a high proportion (83%) of mice. Therefore, increased SAA and/or its dimer in serum during the recovery process may markedly exacerbate the development of AA amyloidosis.

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Mesenchymal Stromal Cell Secretome for the Treatment of Immune-Mediated Inflammatory Diseases: Latest Trends in Isolation, Content Optimization and Delivery Avenues

Pharmaceutics ◽

10.3390/pharmaceutics13111802 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1802

Author(s):

Elena Munoz-Perez ◽

Ainhoa Gonzalez-Pujana ◽

Manoli Igartua ◽

Edorta Santos-Vizcaino ◽

Rosa Maria Hernandez

Keyword(s):

Stromal Cells ◽

State Of The Art ◽

Inflammatory Diseases ◽

Therapeutic Approaches ◽

Pharmacological Management ◽

Beneficial Effects ◽

New Therapeutic Approaches ◽

Immune Mediated ◽

High Prevalence ◽

Inflammatory Processes

Considering the high prevalence and the complex pharmacological management of immune-mediated inflammatory diseases (IMIDs), the search for new therapeutic approaches for their treatment is vital. Although the immunomodulatory and anti-inflammatory effects of mesenchymal stromal cells (MSCs) have been extensively studied as a potential therapy in this field, direct MSC implantation presents some limitations that could slow down the clinical translation. Since the beneficial effects of MSCs have been mainly attributed to their ability to secrete a plethora of bioactive factors, their secretome has been proposed as a new and promising pathway for the treatment of IMIDs. Formed from soluble factors and extracellular vesicles (EVs), the MSC-derived secretome has been proven to elicit immunomodulatory effects that control the inflammatory processes that occur in IMIDs. This article aims to review the available knowledge on the MSC secretome, evaluating the advances in this field in terms of its composition, production and application, as well as analyzing the pending challenges in the field. Moreover, the latest research involving secretome administration in IMIDs is discussed to provide an updated state-of-the-art for this field. Finally, novel secretome delivery alternatives are reviewed, paying special attention to hydrogel encapsulation as one of the most convenient and promising strategies.

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Successful Treatment of AA Amyloidosis in Ankylosing Spondylitis Using Tocilizumab: Report of Two Cases and Review of the Literature

Frontiers in Medicine ◽

10.3389/fmed.2021.661101 ◽

2021 ◽

Vol 8 ◽

Author(s):

Per Eriksson ◽

Johan Mölne ◽

Lina Wirestam ◽

Christopher Sjöwall

Keyword(s):

Ankylosing Spondylitis ◽

Therapeutic Option ◽

Relevant Literature ◽

Acute Phase Reactant ◽

Renal Amyloidosis ◽

Secondary Amyloidosis ◽

Aa Amyloidosis ◽

Beneficial Effects ◽

Amyloid A ◽

Inflammatory Conditions

Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.

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High prevalence ofPneumocystis jiroveciicolonization among patients with autoimmune inflammatory diseases and corticosteroid therapy

Scandinavian Journal of Rheumatology ◽

10.3109/03009742.2011.630328 ◽

2012 ◽

Vol 41 (3) ◽

pp. 208-213 ◽

Cited By ~ 18

Author(s):

C Fritzsche ◽

D Riebold ◽

AK Munk-Hartig ◽

S Klammt ◽

G Neeck ◽

...

Keyword(s):

Corticosteroid Therapy ◽

Inflammatory Diseases ◽

High Prevalence

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Typing of hereditary renal amyloidosis presenting with isolated glomerular amyloid deposition

BMC Nephrology ◽

10.1186/s12882-019-1667-5 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Danyang Li ◽

Dan Liu ◽

Hui Xu ◽

Xiao-juan Yu ◽

Fu-de Zhou ◽

...

Keyword(s):

Gene Mutations ◽

Amyloid Deposition ◽

Renal Diseases ◽

Heterozygous Mutation ◽

Renal Amyloidosis ◽

Aged Patients ◽

Reliable Technique ◽

Dna Mutations ◽

Amyloid Deposits ◽

History Of

Abstract Background The commonly used methods for amyloid typing include immunofluorescence or immunohistochemistry (IHC), which sometimes may come with diagnostic pitfalls. Mass spectrometry (MS)-based proteomics has been recognized as a reliable technique in amyloid typing. Case presentation We reported two middle-aged patients who presented with proteinuria, hypertension and normal renal function, and both had a family history of renal diseases. The renal biopsies of both patients revealed renal amyloidosis with the similar pattern by massive exclusively glomerular amyloid deposition. The IHC was performed by using a panel of antibodies against the common types of systemic amyloidosis, and demonstrated co-deposition of fibrinogen Aα chain and apolipoprotein A-I in the glomerular amyloid deposits of each patient. Then the MS on amyloid deposits captured by laser microdissection (LMD/MS) and genetic study of gene mutations were investigated. The large spectra corresponding to ApoA-I in case 1, and fibrinogen Aα chain in case 2 were identified by LMD/MS respectively. Further analysis of genomic DNA mutations demonstrated a heterozygous mutation of p. Trp74Arg in ApoA-I in case 1, and a heterozygous mutation of p. Arg547GlyfsTer21 in fibrinogen Aα chain in case 2. Conclusions The current study revealed that IHC was not reliable for accurate amyloid typing, and that MS-based proteomics and genetic analysis were essential for typing of hereditary amyloidosis.

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