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

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.

scholarly journals Rituximab Therapy in Renal Amyloidosis Secondary to Rheumatoid Arthritis

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 136 ◽  
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.

scholarly journals Amyloid deposition in granuloma of tuberculosis patients: A pilot study

2021 ◽  
Author(s):  
Shreya Ghosh ◽  
Akansha Garg ◽  
Chayanika Kala ◽  
Ashwani Kumar Thakur
Keyword(s):  
Serum Amyloid A ◽  
Amyloid Deposition ◽  
Serum Amyloid ◽  
Secondary Amyloidosis ◽  
Amyloid Formation ◽  
Tuberculosis Patients ◽  
Amyloid A ◽  
Inflammatory Conditions ◽  
Amyloid Deposits ◽  
Serum Amyloid A Protein

AbstractThe formation of granuloma is one of the characteristic feature of tuberculosis. Besides, rise in the concentration of acute phase response proteins mainly serum amyloid A is the indicator for chronic inflammation associated with tuberculosis. Serum amyloid A drives secondary amyloidosis in tuberculosis and other chronic inflammatory conditions. The linkage between serum amyloid A (SAA) protein and amyloid deposition site is not well understood in tuberculosis and other chronic inflammatory conditions. We hypothesized that granuloma could be a potential site for amyloid deposition because of the presence of serum amyloid A protein and proteases that cleave SAA and trigger amyloid formation. Based on this hypothesis, for the first time we have shown the presence of amyloid deposits in the granuloma of tuberculosis patients using the gold standard, Congo red dye staining.

scholarly journals Systemic Amyloidosis as a Rare Complication of IgG4 Related Disease: Case Report and Literature Review

2021 ◽  
Author(s):  
Leonardo Oliveira Mendonca ◽  
Henrikki Gomes Antila ◽  
Alex Isidoro Prado ◽  
Luiz Augusto Marcondes Fonseca ◽  
Miton de Arruda Martins ◽  
...  
Keyword(s):  
Rare Complication ◽  
Systemic Amyloidosis ◽  
Aa Amyloidosis ◽  
Amyloid A ◽  
Related Disease ◽  
Igg4 Related Disease ◽  
Inflammatory Conditions ◽  
Immune Mediated ◽  
Brazilian Patient ◽  
Disease Case

Abstract Immunoglobulin 4 Related Disease (IgG4-RD) is immune-mediated fibroinflammatory disease and despite recent advances the immunological process involved in the disease pathogenesis is still unclear. Serum amyloid A (SAA) the precursor protein in AA amyloidosis is induced by inflammatory mediators such as IL-1, IL-6 and TNF cytokines. The treatment of AA amyloidosis is directed by the theoretical cytokine involved in the underlying inflammatory condition. Many inflammatory conditions has already been associated to AA amyloidosis and secondary to IgG4-RD seems to be rare. Here we report the case of a Brazilian patient with IgG4-RD with a fatal evolution of systemic amyloidosis. We also revised the cases already reporte in the literature with IgG4-RD and systemic amyloidosis.

Serum amyloid A as a marker of ankylosing spondylitis activity

2021 ◽  
Vol 15 (6) ◽  
pp. 72-75
Author(s):  
K. V. Sakharova ◽  
M. V. Cherkasova ◽  
Sh. F. Erdes
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Significant Relationship ◽  
Serum Amyloid A ◽  
Serum Amyloid ◽  
Secondary Amyloidosis ◽  
High Concentration ◽  
Amyloid A ◽  
Markers Of Inflammation ◽  
Serum Amyloid A Protein

Serum amyloid A protein A (SAA) is a normal serum protein (serving as a precursor of fibrillar tissue protein AA), synthesized in the liver and a rapidly responding marker of the acute phase of inflammation. A constant high concentration of SAA is one of the factors in the development of AA-amyloidosis. As a rule, secondary amyloidosis develops in patients with long-term and poorly controlled inflammatory diseases, including rheumatic diseases, one of which is ankylosing spondylitis (AS).Objective: to assess the level of SAA in AS patients and its relationship with indicators of disease activity.Patients and methods. The study included 124 patients with AS who met the modified New York 1984 criteria. The disease activity and functional status of patients were assessed according to the recommendations of Russian experts. SAA and CRP, ESR in blood serum were measured in all patients.Results and discussion. The median SAA concentration was 12.5 mg/L [4; 71.6]. Of 124 patients, 31% had SAA levels <5 mg/L and 69% had >5 mg/L. A strong correlation was found between the levels of SAA and CRP (r=0.80, p<0.000001), no significant relationship was found between SAA and ESR (r=0.31, p=0.92). The correlation between the AS activity according to the BASDAI index and SAA was weak (r=0.3, p<0.002), the correlation with ASDAS-CRP was moderate (r=0.54, p<0.00001).Conclusion. A statistically significant relationship was found between SAA and CRP levels, as well as the AS activity indices. Research has shown that SAA can be used as one of the markers of inflammation in AS.

scholarly journals AA-amyloidosis in autoinflammatory diseases

2021 ◽  
Vol 31 (4) ◽  
pp. 52-61
Author(s):  
V. Rameev ◽  
S. Moiseev ◽  
L. Lysenko (Kozlovskaya)
Keyword(s):  
Amyloid Fibrils ◽  
Acute Phase Reactant ◽  
Autoinflammatory Diseases ◽  
Aa Amyloidosis ◽  
Chronic Infections ◽  
Amyloid A ◽  
Ankylosing Spondilitis ◽  
Serum Amyloid A Protein ◽  
Treatment Improvement

AA amyloidosis complicates various chronic inflammatory disorders and is characterized by the accumulation of amyloid fibrils composed of serum amyloid A protein, an acute phase reactant. In recent decades, the role of chronic infections and rheumatoid arthritis in the ethiology of AA amyloidosis have decreased significantly as a result of their treatment improvement, whereas both monogenic (familial Meditarranean fever, cryopirin-associated periodic syndrome, etc.) or polygenic (ankylosing spondilitis, psoriatic arthritis, adult onset Still’s disease, etc) autoinflammatory diseases more frequently account for AA-amyloidosis today. Autoinflammatory diseases are a consequence of innate immunity disorders although the latter can contribute to the pathogenesis of autoimmune diseases as well. In patients with autoinflammatory diseases, the suppression of inflammation, even subclinical, is essential to prevent development or progression of AA amyloidosis. The choice of inflammatory agents that can be used to achieve this aim depends on the pathogenesis of autoinflammation, e.g. key mediators that are involved in the activation of inflammatory cascade.

scholarly journals Impaired Kupffer cell function precedes development of secondary amyloidosis.

1985 ◽  
Vol 161 (5) ◽  
pp. 1013-1028 ◽  
Author(s):  
A Fuks ◽  
D Zucker-Franklin
Keyword(s):  
Cell Function ◽  
Surface Membrane ◽  
Protein A ◽  
Acute Phase Reactant ◽  
Cleavage Product ◽  
Secondary Amyloidosis ◽  
Blood Monocytes ◽  
Amyloid A ◽  
Sds Page

It has been demonstrated previously that the acute phase reactant, serum amyloid A (SAA), is subject to degradation by surface membrane-associated proteinases of peripheral blood monocytes. However, monocytes obtained from the blood of patients with amyloidosis degraded SAA incompletely, leaving a cleavage product that, biochemically and immunologically, resembled the amyloid protein A (AA) deposited in their tissues. To investigate the role of fixed macrophages in amyloidogenesis and to establish more definitively that amyloid deposition is attributable to faulty processing of the precursor protein rather than aberrant synthesis, secondary amyloidosis was induced in C57BL/6J mice by serial injections of casein. Kupffer cells (KC) were isolated from livers of mice that had received 0, 8, 13, 18, and greater than 30 injections of the stimulant. The cells were cultured with SAA for 4, 8, and 18 h and then subjected to electron microscopy and enzyme analyses. The medium was analyzed by SDS-PAGE to determine the amount of residual SAA and/or the appearance of AA. KC of healthy animals degraded SAA completely whereas KC of stimulated mice showed increasing amounts of residual SAA and the appearance of the AA cleavage product. The AA peptide appeared in KC cultures early during the course of casein injections and before any amyloid could be demonstrated in the organs of the stimulated mice. The addition of KC isolated from healthy mice to cultures that had produced AA eliminated the abnormal peptide. The results, indicate that defective KC function precedes amyloidosis. The abnormal AA cleavage product formed by such cells is still susceptible to hydrolysis by normal cells. In addition, ultrastructural evidence is presented that suggests that KC may also play a role in fibrillogenesis of the AA protein.

scholarly journals Familial Renal Amyloidosis in Abyssinian Cats

1984 ◽  
Vol 21 (1) ◽  
pp. 33-38 ◽  
Author(s):  
J. T. Boyce ◽  
S. P. DiBartola ◽  
D. J. Chew ◽  
P. W. Gasper
Keyword(s):  
Potassium Permanganate ◽  
Congo Red ◽  
Amyloid Deposition ◽  
Renal Amyloidosis ◽  
Secondary Amyloidosis ◽  
Section Thickness ◽  
Papillary Necrosis ◽  
Permanganate Oxidation ◽  
Amyloid A ◽  
Interstitial Disease

Medullary and glomerular amyloidosis, papillary necrosis, and secondary interstitial disease were diagnosed in eight related adult Abyssinian cats from two catteries. The lesions were similar to those in two unrelated mongrel cats with renal amyloidosis. Ultrastructurally, the patterns of amyloid deposition were as described in other species, although medullary deposition predominated. Potassium permanganate oxidation blocked Congo red staining of the deposits suggesting that they contained amyloid A protein (secondary amyloid). The disease may be a model of familial secondary amyloidosis and offers an opportunity to study the pathogenesis of both amyloid deposition and papillary necrosis. The histochemical characteristics of feline renal amyloid require careful attention to technique. Section thickness affects Congo red affinity and both dichroism as well as birefringence should be considered when interpreting staining reactions. Thioflavine-T may be the preferred stain for identification of small deposits of amyloid. Variation in section thickness markedly affected the degree of potassium permanganate oxidation.

scholarly journals A case of effective use of interleukin 6 inhibitors in patients with ankylosing spondylitis with secondary amyloidosis

2021 ◽  
Vol 15 (4) ◽  
pp. 38-42
Author(s):  
Sh. F. Erdes ◽  
D. G. Rumyantseva ◽  
E. M. Agafonova ◽  
M. M. Urumova ◽  
A. S. Starkova ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Interleukin 6 ◽  
Randomized Clinical Trials ◽  
Average Duration ◽  
Disease Onset ◽  
Inflammatory Back Pain ◽  
Secondary Amyloidosis ◽  
Aa Amyloidosis ◽  
Ample Evidence ◽  
Number Of Patients

Ineffectiveness of interleukin 6 inhibitors (iIL6), tocilizumab (TCZ) and sarilimumab in ankylosing spondylitis (AS) was shown in randomized clinical trials. However, there is ample evidence that IL6 is actively involved in the pathogenesis of this disease. In addition, the efficacy of iIL6 in patients with secondary AA-amyloidosis was established.Objective: to analyze the results of TCZ administration in AS, complicated by secondary AA-amyloidosis.Patients and methods. The analysis included 6 patients with AS with secondary AA-amyloidosis. All patients were HLA-B27 positive male. The average age of patients was 44±9.2 years, the average age of the disease onset was 16.3±7.9 years, the average duration of AS was 26.0±7.5 years. All 6 patients had pathomorphologic confirmed secondary AA-amyloidosis: all had kidney affection, 5 patients also had gastrointestinal tract affection and 2 had heart affection. As a first biological drug TCZ was prescribed in 2 patients, and 4 patients had previously received one or more inhibitors of tumor necrosis factor α. The average duration of TCZ treatment was 27.6 [3.0; 36.0] months.Results and discussion. During TCZ therapy, the level of CRP (M±σ) significantly decreased: from 81.1±74.5 to 1.2±0.8 mg/L (p<0.05), as well as daily proteinuria (Me [25th ; 75th percentile]): from 1.8 [1.0; 2.1] to 0.2 [0.1; 0.3] g/day (p<0.05) and AS activity indices – BASDAI (M±σ): from 6.2±1.6 to 3.3±0.9 (p<0.05 ); ASDAS-CRP (M±σ) from 4.6±1.1 to 2.04±0.7 (p<0.05). Positive dynamics was also noted in relation to a decrease in the number of patients with inflammatory back pain, arthritis and coxitis. A case of clinical and laboratory remission of AS on TCZ treatment is described. Conclusion. The presented data show that in certain clinical situations iIL6 can be highly effective in AS.

scholarly journals Revisiting renal amyloidosis with clinicopathological characteristics, grading, and scoring: A single-institutional experience

2018 ◽  
Vol 10 (02) ◽  
pp. 226-231 ◽  
Author(s):  
Abhiram Kalle ◽  
Archana Gudipati ◽  
Sree Bhushan Raju ◽  
Karthik Kalidindi ◽  
Swarnalatha Guditi ◽  
...  
Keyword(s):  
Renal Biopsy ◽  
Microscopic Analysis ◽  
Clinical History ◽  
Clinicopathological Characteristics ◽  
Renal Amyloidosis ◽  
Secondary Amyloidosis ◽  
Amyloid A ◽  
Kidney Involvement ◽  
Wide Range ◽  
Glomerular Involvement

Abstract INTRODUCTION: Kidney involvement is a major cause of mortality in systemic amyloidosis. Glomerulus is the most common site of deposition in renal amyloidosis, and nephrotic syndrome is the most common presentation. Distinction between AA and AL is done using immunofluorescence (IF) and immunohistochemistry (IHC). Renal biopsy helps in diagnosis and also predicting the clinical course by applying scoring and grading to the biopsy findings. MATERIALS AND METHODS: The study includes all cases of biopsy-proven renal amyloidosis from January 2008 to May 2017. Light microscopic analysis; Congo red with polarization; IF; IHC for Amyloid A, kappa, and lambda; and bone marrow evaluation were done. Classification of glomerular amyloid deposition and scoring and grading are done as per the guidelines of Sen S et al. RESULTS: There are 40 cases of biopsy-proven renal amyloidosis with 12 primary and 23 secondary cases. Mean age at presentation was 42.5 years. Edema was the most common presenting feature. Secondary amyloidosis cases were predominant. Tuberculosis was the most common secondary cause. Multiple myeloma was detected in four primary cases. Grading of renal biopsy features showed a good correlation with the class of glomerular involvement. CONCLUSION: Clinical history, IF, and IHC are essential in amyloid typing. Grading helps provide a subtle guide regarding the severity of disease in the background of a wide range of morphological features and biochemical values. Typing of amyloid is also essential for choosing the appropriate treatment.

scholarly journals Serum Amyloid A Level in Egyptian Children with Familial Mediterranean Fever

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Hala M. Lofty ◽  
Huda Marzouk ◽  
Yomna Farag ◽  
Mohammad Nabih ◽  
Iman A. S. Khalifa ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Serum Amyloid A ◽  
Acute Phase Reactant ◽  
Serum Amyloid ◽  
Amyloid A ◽  
Inflammatory Conditions ◽  
Phase Reactant ◽  
Egyptian Children ◽  
Mediterranean Fever ◽  
Colchicine Therapy

Background and Objectives. SAA is an acute-phase reactant detected during an FMF attack or other inflammatory conditions. High SAA levels may increase the risk of amyloidosis. The aim of the study is to measure the serum amyloid A (SAA) level in a group of Egyptian children with familial Mediterranean fever (FMF) and study its various correlates, if any.Methods. The study enrolled seventy-one children with FMF.Results. SAA level was high in 78.9% of the studied patients with a mean of81.62±31.6 mg/L, and CRP was positive in 31% of patients. There was no significant releation between SAA level and any demographic or clinical manifestation. High SAA was more frequent in V726A allele (16.9%) followed by M694V allele (12.3%). Elevated SAA levels were more frequent in patients on low colchicine doses. Forty-five percent (45%) of patients have low adherence to colchicine therapy.Interpretation and Conclusion. High SAA levels were detected two weeks after last FMF attack in a large percentage of Egyptian FMF children. This indicates that subclinical inflammation continues during attack-free periods, and SAA could be used as a marker of it.

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