Search

Systemic amyloid A (AA) amyloidosis, which is considered the second most common form of systemic amyloidosis usually takes place several years prior to the occurrence of chronic inflammation, generally involving the kidney. Activated HSF1, which alleviated unfolded protein response (UPR) or enhanced HSR, is the potential therapeutic target of many diseases. However, the effect of HSF1 on AA amyloidosis remains unclear. This study focused on evaluating effect of HSF1 on AA amyloidosis based on HSF1 knockout mice. As a result, aggravated amyloid deposits and renal dysfunction have been found in HSF1 knockout mice. In progressive AA amyloidosis, HSF1 deficiency enhances serum amyloid A production might to lead to severe AA amyloid deposition in mice, which may be related to deactivated unfolded protein response as well as enhanced inflammation. Thus, HSF1 plays a significant role on UPR related pathway impacting AA amyloid deposition, which can mitigate amyloidogenic proteins from aggregation pathologically and is the possible way for intervening with the pathology of systemic amyloid disorder. In conclusion, HSF1 could not only serve as a new target for AA amyloidosis treatment in the future, but HSF1 knockout mice also can be considered as a valuable novel animal model for renal AA amyloidosis. [ABSTRACT FROM AUTHOR]

Amyloidosis is characterized by the extracellular accumulation of abnormal fibrillar proteins in various tissue and organs of the body. Systemic or localized involvement can be seen in various organs, often depending on the underlying disease such as plasma cell myeloma or chronic inflammatory and autoimmune diseases. Amyloid deposition in the breast is rare and may present similar appearance to areas of fat necrosis with fibroelastotic stromal changes in the breast. The amyloid tumor in the breast presented in a 49-year-old female patient diagnosed with multiple sclerosis is a good example of this. Therefore, since amyloid deposition in the breast is an entity that should be kept in mind, the case was deemed worth presenting. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to evaluate the clinical, laboratory and genetic characteristics and outcomes of patients with AA amyloidosis. Methods Patients followed up in a tertiary referral centre in Turkey with the diagnosis of inflammatory rheumatic diseases and immunohistologically proven AA amyloidosis were included in the study and retrospectively analysed. Results Among 184 patients with the diagnosis of AA amyloidosis, 174 (83 female, 91 male) were included in the analysis. The most common cause of AA amyloidosis was FMF (78.7%), and 91% of FMF-AA amyloidosis patients were carrying the p.M694V variant (74.1% homozygous). AA amyloidosis was identified earlier in patients with homozygous or compound heterozygous MEFV exon 10 variants compared with the heterozygous patients (27, 30 and 41 years, respectively). Patients with an estimated glomerular filtration rate <60 ml/min at admission had a higher frequency of progression to end-stage renal disease (P  < 0.001). The overall mortality rate was 15.3% and it increased gradually in association with the amyloid burden (10% in patients with renal, 15% in renal + gastrointestinal and 43% in those with additional cardiac involvement). Renal findings responded completely to treatment in 31% of the patients, a partial response was observed in 4%, a stable course in 23.6% and progression in 38.5%. Amyloid storm was identified in nine patients and was found to be associated with increased mortality within 1 year. Conclusion FMF patients still constitute the majority of AA amyloidosis patients in Turkey. The MEFV genotype and associated inflammatory load may affect the age of onset of AA amyloidosis, and earlier diagnosis and stricter follow-up and treatment may delay progression of the disease. [ABSTRACT FROM AUTHOR]

Renal amyloid-associated (AA) amyloidosis is a harmful complication of familial Mediterranean fever (FMF). Its occurrence involves polymorphisms and mutations in the Serum Amyloid A1 (SAA1) and Mediterranean Fever (MEFV) genes, respectively. In Algeria, the association between SAA1 variants and FMF-related amyloidosis was not investigated, hence the aim of this case-control study. It included 60 healthy controls and 60 unrelated FMF patients (39 with amyloidosis, and 21 without amyloidosis). All were genotyped for the SAA1 alleles (SAA1.1, SAA1.5, and SAA1.3), and a subset of them for the − 13 C/T polymorphism by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Comparisons between genotype and allele frequencies were performed using Chi-square and Fisher tests. The SAA1.1/1.1 genotype was predominant in amyloid FMF patients, compared to non-amyloid FMF patients (p = 0.001) and controls (p < 0.0001). SAA1.1/1.5 was higher in non-amyloid patients (p = 0.0069) and in controls (p = 0.0082) than in patients with amyloidosis. Bivariate logistic regression revealed an increased risk of AA amyloidosis with three genotypes, SAA1.1/1.1 [odds ratio 7.589 (OR); 95% confidence interval (CI): 2.130-27.041] (p = 0.0018), SAA1.1/1.3 [OR 5.700; 95% CI: 1.435–22.644] (p = 0.0134), and M694I/M694I [OR 4.6; 95% CI: 1.400-15.117] (p = 0.0119). The SAA1.1/1.5 genotype [OR 0.152; 95% CI: 0.040–0.587] (p = 0.0062) was protective against amyloidosis. In all groups, the − 13 C/C genotype predominated, and was not related to renal complication [OR 0.88; 95% CI: 0.07–10.43] (p = 0.915). In conclusion, in contrast to the − 13 C/T polymorphism, the SAA1.1/1.1, SAA1.1/1.3 and M694I/M694I genotypes may increase the risk of developing renal AA amyloidosis in the Algerian population. [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever is the most common monogenic auto-inflammatory disease in the world. It mainly affects people originating from the Mediterranean region. The mutated gene is MEFV , which codes for pyrin. Transmission is autosomal recessive. Patients present with recurrent attacks of fever since childhood associated with abdominal and/or thoracic pain lasting an average of 2–3 days and a biological inflammatory syndrome. Other symptoms include arthralgia or arthritis in large joints such as the knees and ankles, myalgia in the lower limbs and pseudo-erysipelas in the ankles. The most serious complication is inflammatory amyloidosis, which can lead to kidney failure. Treatment is based on colchicine, which helps to prevent flares and the onset of renal amyloidosis. This paper proposes national guidelines for the diagnosis, management and follow-up of familial Mediterranean fever in France, where we estimate there are between 5000 and 10,000 patients with the disease at all stages of life. The diagnosis is suspected on the basis of clinical and anamnestic factors and confirmed by genetic analysis. These guidelines also suggest a "treat-to-target" approach to disease management, particularly in case of suspected colchicine resistance – a very rare situation that should remain a diagnosis of elimination, especially after colchicine compliance has been verified. Two special situations are also addressed in these guidelines: kidney failure and pregnancy. [ABSTRACT FROM AUTHOR]

Amyloidosis is an infiltrative disease caused by misfolded proteins depositing in tissues. Amyloid infiltrates the kidney in several patterns. There are, as currently described by the International Society of Amyloidosis, 14 types of amyloid that can involve the kidney, and these types may have different locations or clinical settings. Herein we report a case of AA amyloidosis occurring in a 24-year-old male with a history of intravenous drug abuse and provide a comprehensive review of different types of amyloids involving the kidney.

Autoinflammatory diseases (AIDs) are mostly caused by dysfunctions in single genes encoding for proteins with a prominent role in the regulation of innate immunity, such as complement factors, inflammasome components, tumour necrosis factor (TNF)‐α, and proteins belonging to type I‐interferon (IFN) signalling pathways. Due to the deposition of amyloid A (AA) fibrils in the glomeruli, unprovoked inflammation in AIDs frequently affects renal health. In fact, secondary AA amyloidosis is the most common form of amyloidosis in children. It is caused by the extracellular deposition of fibrillar low‐molecular weight protein subunits resulting from the degradation and accumulation of serum amyloid A (SAA) in numerous tissues and organs, primarily the kidneys. The molecular mechanisms underlying AA amyloidosis in AIDs are the elevated levels of SAA, produced by the liver in response to pro‐inflammatory cytokines, and a genetic predisposition due to specific SAA isoforms. Despite the prevalence of amyloid kidney disease, non‐amyloid kidney diseases may also be responsible for chronic renal damage in children with AIDs, albeit with distinct characteristics. Glomerular damage can result in various forms of glomerulonephritis with distinct histologic characteristics and a different underlying pathophysiology. This review aims to describe the potential renal implications in patients with inflammasomopathies, type‐I interferonopathies, and other rare AIDs in an effort to improve the clinical course and quality of life in paediatric patients with renal involvement. Summary at a glance: The aim of this review is to describe the genetic background, clinical manifestations, and molecular mechanisms of renal involvement in autoinflammatory diseases. An up‐to‐date knowledge of the most common histopathologic features and correct treatment strategies is essential for a correct work‐up and a good clinical prognosis for renal health. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome is a chronic inflammatory disorder mostly involving the exocrine glands. Extraglandular disease may occur in up to one quarter of patients. Kidney involvement is rare, more often manifested by tubular dysfunction secondary to tubulointerstitial nephritis. Primary glomerular disease is uncommon. The authors present the case of a 73-year-old woman with xerostomia and positivity for anti-Ro and anti-La antibodies admitted for acute kidney injury and exudative pleural effusion. Biopsy of salivary glands was compatible with Sjögren's syndrome. Extraglandular involvement was also confirmed by renal and pleural deposition of AA-amyloid. The patient was started on prednisolone followed by azathioprine with rapid improvement of lung disease. However, due to progressing renal disease and clinical deterioration, prognosis was guarded and the patient died. We describe a case of secondary amyloidosis with systemic involvement and infrequent clinical manifestations, briefly reviewing the key aspects of Sjögren's syndrome and AAamyloidosis. [ABSTRACT FROM AUTHOR]

A 72-year-old woman was urgently hospitalized with a diagnosis of enteritis and subileus. Her past history was as follows. Right radical nephrectomy had been performed 14 years ago, and the pathological diagnosis was clear cell carcinoma (G2>G3). Four years later, she suffered from mulitiple lung and bone metastases and had been treated with a total of 7 courses of combination therapy with sorafenib and S-1, but the disease progressed within 1 year. Then, axitinib was started, and this stabilized her disease for 9 years. Watery stools and hypoalbuminemia continued even after quitting axitinib. A small bowel biopsy was performed, and she was diagnosed with protein-losing gastroenteropathy associated with AA amyloidosis. Gallium scintigraphy showed accumulation in the femur, and she was diagnosed with AA amyloidosis associated with bone metastasis of renal cell carcinoma. Radiation therapy to the femur relieved her symptoms just temporarily. She died of the disease one week later. AA amyloidosis belongs to systemic amyloidosis and is a disease in which amyloid protein is deposited in organs and causes damage. Cancer-related systemic amyloidosis accounts for seven percent of the total cases, and renal cell carcinoma is the most common among solid tumors. Control of the primary disease is most important for calming the symptoms of amyloidosis. [ABSTRACT FROM AUTHOR]

Systemic AA amyloidosis is associated with systemic inflammatory processes such as autoimmune disorders or chronic infections. In addition, AA amyloidosis can develop in a localized or systemic form in patients with malignant neoplastic disorders, and usually involves kidneys impacting renal function. Among solid tumors, renal cell carcinoma (RCC) appears to be responsible for one-quarter to half of all cancers associated with amyloidosis. Among other solid cancers, various clinical presentations and pathological types of lung cancer and basal cell carcinoma skin were reported with AA amyloidosis more often than isolated case reports on other cancers with AA amyloidosis. Symptoms from kidney involvement rather than from the tumor per se were the presenting manifestations in cases of RCC associated with AA amyloidosis. Among hematological malignancies, clonal B cell/plasma cell dyscrasias such as monoclonal gammopathy and lymphoma were noted to be associated with AA amyloidosis. In addition, AA amyloidosis was reported in a substantial number of cases treated with immune checkpoint inhibitors such as pembrolizumab and nivolumab. The mechanism of association of cancer and AA amyloidosis seems to be mediated by the immune response exacerbated from the tumor and its microenvironment or immune therapy. The mainstay of treatment consists of therapy directed against the underlying malignancy or careful withdrawal of the offending agent. This review will discuss this rare but highly morbid clinical condition. [ABSTRACT FROM AUTHOR]

Abstract Background Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients´ medical records were retrospectively reviewed. Results One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, ≥ 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had ≥ 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I–II, respectively (p

AA amyloidosis may complicate several chronic inflammatory conditions. From a clinical point of view, causality between inflammatory pathology and AA amyloidosis can be assumed because of the data described in the literature; some of the best known include rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and chronic infections. Singles cases of inflammatory diseases have been found at AA amyloidosis. Causality becomes more plausible if at least two different cases with AA amyloidosis are both found to have the same rare inflammatory disease. We describe the case of a patient with primary sclerosing cholangitis (PSC) with development of AA amyloidosis conditioning a nephrotic syndrome, likely secondary to failure to control the chronic inflammatory process. Only two cases in the literature describe the association of this rare disease and the appearance of AA amyloidosis. The treatment of AA amyloidosis consists in treating the underlying inflammatory disorder; to date, few effective treatments are available for PSC. Therefore, and in view of the limited data in the literature, we believe it is important to describe its association.

AA amyloidosis is secondary to the deposit of excess insoluble Serum Amyloid A (SAA) protein fibrils. AA amyloidosis complicates chronic inflammatory diseases, especially chronic inflammatory rheumatisms such as rheumatoid arthritis and spondyloarthritis; chronic infections such as tuberculosis, bronchectasia, chronic inflammatory bowel diseases such as Crohn's disease; and auto-inflammatory diseases including familial Mediterranean fever. This work consists of the French guidelines for the diagnosis workup and treatment of AA amyloidosis. We estimate in France between 500 and 700 cases in the whole French population, affecting both men and women. The most frequent organ impaired is kidney which usually manifests by oedemas of the lower extremities, proteinuria, and/or renal failure. Patients are usually tired and can display digestive features anf thyroid goiter. The diagnosis of AA amyloidosis is based on detection of amyloid deposits on a biopsy using Congo Red staining with a characteristic green birefringence in polarized light. Immunohistochemical analysis with an antibody directed against Serum Amyloid A protein is essential to confirm the diagnosis of AA amyloidosis. Peripheral inflammatory biomarkers can be measured such as C Reactive protein and SAA. We propose an algorithm to guide the etiological diagnosis of AA amyloidosis. The treatement relies on the etiologic treatment of the undelying chronic inflammatory disease to decrease and/or normalize Serum Amyloid A protein concentration in order to stabilize amyloidosis. In case of renal failure, dialysis or even a kidney transplant can be porposed. Nowadays, there is currently no specific treatment for AA amyloidosis deposits which constitutes a therapeutic challenge for the future. [ABSTRACT FROM AUTHOR]

Objective A decline in the frequency of AA amyloidosis secondary to RA and infectious diseases has been reported. We aimed to determine the change in the frequency of AA amyloidosis in our Behçet's syndrome (BS) patients and to summarize the clinical characteristics of and outcomes for our patients, and also those identified by a systematic review. Methods We identified patients with amyloidosis in our BS cohort (as well as their clinical and laboratory features, treatment, and outcome) through a chart review. The primary end points were end-stage renal disease and death. The prevalence of AA amyloidosis was estimated separately for patients registered during 1976–2000 and those registered during 2001–2017, in order to determine whether there was any change in the frequency. We searched PubMed and EMBASE for reports on BS patients with AA amyloidosis. Risk of bias was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. Results The prevalence of AA amyloidosis was 0.62% (24/3820) in the earlier cohort and declined to 0.054% (3/5590) in the recent cohort. The systematic review revealed 82 cases in 42 publications. The main features of patients were male predominance and a high frequency of vascular involvement. One-third of patients died within 6 months after diagnosis of amyloidosis. Conclusion The frequency of AA amyloidosis has decreased in patients with BS, which is similar to the decrease observed for AA amyloidosis due to other inflammatory and infectious causes. However, AA amyloidosis is a rare, but potentially fatal complication of BS. [ABSTRACT FROM AUTHOR]

Sjögren’s syndrome is a chronic inflammatory disorder mostly involving the exocrine glands. Extraglandular disease may occur in up to one quarter of patients. Kidney involvement is rare, more often manifested by tubular dysfunction secondary to tubulointerstitial nephritis. Primary glomerular disease is uncommon. The authors present the case of a 73-year-old woman with xerostomia and positivity for anti-Ro and anti-La antibodies admitted for acute kidney injury and exudative pleural effusion. Biopsy of salivary glands was compatible with Sjögren’s syndrome. Extraglandular involvement was also confirmed by renal and pleural deposition of AA-amyloid. The patient was started on prednisolone followed by azathioprine with rapid improvement of lung disease. However, due to progressing renal disease and clinical deterioration, prognosis was guarded and the patient died. We describe a case of secondary amyloidosis with systemic involvement and infrequent clinical manifestations, briefly reviewing the key aspects of Sjögren’s syndrome and AA-amyloidosis.

BackgroundSkin and soft tissue infections (SSTIs) are a leading cause of morbidity and mortality among people who inject drugs (PWID). International data indicate up to one third of PWID have experienced an SSTI within the past month. Complications include sepsis, endocarditis and amyloid A (AA) amyloidosis. AA amyloidosis is a serious sequela of chronic SSTI among PWID. Though there is a paucity of literature reporting on AA amyloidosis among PWID, what has been published suggests there is likely a causal relationship between AA amyloidosis and injecting-related SSTI. If left untreated, AA amyloidosis can lead to renal failure; premature mortality among diagnosed PWID is high. Early intervention may reverse disease. Despite the high societal and individual burden of SSTI among PWID, empirical evidence on the barriers and facilitators to injecting-related SSTI prevention and care or the feasibility and acceptability of AA amyloidosis screening and treatment referral are limited. This study aims to fill these gaps and assess the prevalence of AA amyloidosis among PWID.MethodsCare and Prevent is a UK National Institute for Health Research-funded mixed-methods study. In five phases (P1-P5), we aim to assess the evidence for AA amyloidosis among PWID (P1); assess the feasibility of AA amyloidosis screening, diagnostic and treatment referral among PWID in London (P2); investigate the barriers and facilitators to AA amyloidosis care (P3); explore SSTI protection and risk (P4); and co-create harm reduction resources with the affected community (P5). This paper describes the conceptual framework, methodological design and proposed analysis for the mixed-methods multi-phase study.ResultsWe are implementing the Care and Prevent protocol in London. The systematic review component of the study has been completed and published. Care and Prevent will generate an estimate of AA amyloidosis prevalence among community recruited PWID in London, with implications for the development of screening recommendations and intervention implementation. We aim to recruit 400 PWID from drug treatment services in London, UK.ConclusionsCare and Prevent is the first study to assess screening feasibility and the prevalence of positive proteinuria, as a marker for AA amyloidosis, among PWID accessing drug treatment services. AA amyloidosis is a serious, yet under-recognised condition for which early intervention is available but not employed.

Background: Systemic amyloidosis is caused by the deposition of misfolded protein aggregates in tissues, leading to progressive organ dysfunction and death. Epidemiological studies originate predominantly from high-income countries, with few data from Latin America. Due to the non-specific clinical manifestations, diagnosing amyloidosis is often challenging and patients experience a long journey and delay in diagnosis. This study aimed to assess clinical and laboratory characteristics, the diagnostic journey, and outcomes of patients with biopsy-proven systemic amyloidosis diagnosed between 2009 and 2020 at a university referral center in a middle-income Latin American country. Patients´ medical records were retrospectively reviewed.Results: One hundred and forty-three patients were included. The median age at diagnosis was 60 years and 54% were male. Until the diagnosis, most of the patients (52%) were seen by at least 3 specialists, the main ones being: general practitioners (57%), nephrologists (45%), and cardiologists (38%). The most common manifestations were renal (54%) and cardiac (41%) disorders, and cachexia was seen in 36% of patients. In 72% of the cases, ≥ 2 biopsies were required until the final diagnosis. The median time from symptoms onset to diagnosis was 10.9 months, and most patients (75%) had ≥ 2 organs involved. The following subtypes were identified: AL (68%), ATTR (13%), AA (8%), AFib (4%), and inconclusive (7%). Median OS was 74.3 months in the non-AL subgroup and 18.5 months in AL. Among AL patients, those with advanced cardiac stage had the worst outcome [median OS 8.6 months versus 52.3 for stage III versus I-II, respectively (p < 0.001)]. AL subtype, cardiac involvement, and ECOG ≥ 2 were identified as independent risk factors for reduced survival.Conclusions: Systemic amyloidosis is still an underdiagnosed condition and the delay in its recognition leads to poor outcomes. Medical education, better diagnostic tools, improvement in access to therapies, and establishment of referral centers may improve patient outcomes in middle-income countries. [ABSTRACT FROM AUTHOR]

Objective Cryopyrin-associated periodic syndrome (CAPS) is a rare but treatable inherited autoinflammatory condition including familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS) and chronic infantile neurologic cutaneous articular syndrome (CINCA). Our objective was to describe the main features of CAPS AA amyloidosis (AA-CAPS) associated and the efficacy of IL-1 inhibitors in this indication. Methods Retrospective study in France associated with a systematic literature review. Results Eighty-six patients were identified: 23 new French cases and 63 from the literature, with a median age at amyloidosis diagnosis of 39 years old. CAPS subtypes were MWS (n  = 62), FCAS (n  = 9), frontier forms between MWS and FCAS (n  = 12) and between CINCA and MWS (n  = 3). NLRP3 had been sequenced in 60 patients (70%) and the most frequent mutation was R260W (60%). Three AA-CAPS patients displayed somatic NLRP3 mutations. Death occurred in 35 patients (41%), none of whom having ever received IL-1 inhibitors. Twenty-eight patients (33%) received IL-1 inhibitors, with a >50% decrease in proteinuria in 89% of cases. Conclusion AA amyloidosis can occur in nearly all CAPS subtypes. IL-1 inhibitors are effective, underlining the necessity of an early diagnosis of CAPS in order to start this treatment as soon as possible among AA-CAPS patients. [ABSTRACT FROM AUTHOR]

Signal peptide (SP) plays an important role in membrane targeting for insertion of secretory and membrane proteins during translocation processes in prokaryotes and eukaryotes. Beside the targeting functions, SP has also been found to affect the stability and folding of several proteins. Serum amyloid A (SAA) proteins are apolipoproteins responding to acute‐phase inflammation. The fibrillization of SAA results in a protein misfolding disease named amyloid A (AA) amyloidosis. The main disease‐associated isoform of human SAA, SAA1.1, is expressed as a precursor protein with an N‐terminal signal peptide composed of 18 residues. The cleavage of the SP generates mature SAA1.1. To investigate whether the SP affects properties of SAA1.1, we systematically examined the structure, protein stability, and fibrillization propensity of pre‐SAA1.1, which possesses the SP, and Ser‐SAA1.1 without the SP but containing with an additional N‐terminal serine residue. We found that the presence of the SP did not significantly affect the predominant helical structure but changed the tertiary conformation as evidenced by intrinsic fluorescence and exposed hydrophobic surfaces. Pre‐SAA1.1 and Ser‐SAA1.1 formed distinct oligomeric assemblies in which pre‐SAA1.1 populated as tetramer and octamer, whereas Ser‐SAA1.1 existed as a predominant hexamer. Pre‐SAA1.1 was found significantly more stable than Ser‐SAA1.1 upon thermal and chemical unfolding. Ser‐SAA1.1, but not pre‐SAA1.1, is capable of forming amyloid fibrils in protein misfolding study, indicating a protective role of the SP. Altogether, our results demonstrated a novel role of the SP in SAA folding and misfolding and provided a novel direction for therapeutic development of AA amyloidosis. [ABSTRACT FROM AUTHOR]

Orbital AA amyloidosis can induce a local inflammatory response, manifesting as orbital swelling, papillitis, posterior scleritis, choroiditis, and exudative retinal detachment. Choriocapillaris vasoocclusion with reactive inflammation to the presence of amyloid fibrils likely underlies this presentation. Purpose: To describe a case of amyloid A protein amyloidosis that produced an orbital inflammatory response with a novel presentation. Methods: Case report. Results: A 24-year-old Caucasian women with a history of intravenous heroin use was hospitalized for tricuspid valve endocarditis and methicillin-resistant Staphylococcus aureus bacteremia, as well as acute renal failure. She received hemodialysis and intravenous daptomycin and had negative blood cultures for 3 weeks, when she developed sudden bilateral orbital swelling and blurred vision. Visual acuity was 20/200 in the right eye and 20/400 in the left eye. Examination revealed proptosis, conjunctival chemosis and desiccation, optic disk swelling, creamy choroidal infiltrates, and inferiorly located exudative retinal detachments in both eyes. Multimodal imaging demonstrated thickening of the sclera, choroid, and choriocapillaris as well as outer retinal disruption, subretinal fluid, and deposits of hyperfluorescent debris within the choriocapillaris, outer retina, and vitreous. Oral prednisone at 60 mg per day resolved the choroidal infiltrates and exudative detachments. Persistent nephrotic syndrome called for a renal biopsy, which demonstrated amyloid A protein amyloidosis. Conclusion: Orbital and choroidal Amyloid A protein amyloidosis can induce a local inflammatory response manifesting as orbital swelling, papillitis, posterior scleritis, choroiditis, and exudative retinal detachment, which responds to steroid therapy. The underlying pathology is likely a reactive inflammatory, vasoocclusive process involving the choriocapillaris and orbital vasculature to the presence of amyloid fibrils. [ABSTRACT FROM AUTHOR]

Systemic amyloidosis has been described in many animals and the most common form is reactive systemic AA amyloidosis. However, cardiac amyloidosis leading to heart failure is rare in animals. We now describe systemic and cardiac amyloidosis in two captive endangered Celebes crested macaques (Macaca nigra) at the Singapore Zoo. Both animals were geriatric and had chronic morbidities. Physical examination, radiography and ultrasonography revealed cardiac arrhythmia, pleural effusion, pulmonary oedema and ascites, consistent with cardiac failure. Amyloidosis was suspected and confirmed as type AA by immunohistochemistry. [ABSTRACT FROM AUTHOR]

Grey seal (Halichoerus grypus) entrapment in fishing gear is well documented, consisting of two forms: peracute underwater entrapment and chronic entanglement. We now highlight a previously undescribed sequela to chronic entanglement in a female grey seal estimated to be at least 2 years of age. The animal was first observed in September 2018 on the coast of north Cornwall, southwest England, with a large encircling neck wound consistent with monofilament net entanglement. In April 2021, it was admitted for attempted rehabilitation but had to be euthanized after 9 days due to clinical deterioration despite treatment. At post-mortem examination, the seal was in poor nutritional state, the nose to flipper length was low for its estimated age and the liver was markedly enlarged, pale and friable in texture with evidence of recent and previous hepatic haemorrhage. Histopathology revealed hepatic amyloidosis and evidence of amyloid in one kidney and one adrenal gland. Proteomic analysis of microdissected amyloid from the liver indicated type AA amyloid. Chronic entanglement is the most plausible cause of AA amyloidosis in this animal, indicating that amyloidosis should be considered as a pathological sequela and welfare concern associated with chronic entanglement of grey seals. [ABSTRACT FROM AUTHOR]

Aim: We aimed to evaluate clinicopathological features in patients with renal amyloid A (AA) amyloidosis to analyze the impact of renal biopsy on renal and patient outcomes. Materials and Methods: We retrospectively collected data regarding baseline and follow-up clinical and laboratory features. The same pathologist scored each kidney biopsy specimen according to amyloid distrubition and amount with tubulointerstitial findings. We added all scores and obtained renal amyloid prognostic score (RAPS) and then divided patients into three RAPS grades (RAPS grade I, II, III). Results: Eighteen patients (male, 72.2%) with a median age of 51.5 (IQR, 45-58.3) years were included in the study. The most common disease related to AA amyloidosis was previous tuberculosis (33.3%). Median serum creatinine of patients at renal biopsy time was 1.61 (IQR, 0.91-2.89) mg/dL with a median 24-h protein excretion, 6.8 [IQR, 4.6-8.9] g/day. 100%, 94.4%, 55.6% of patients' renal biopsies had vascular, glomerular (mostly diffuse mesangiocapillary) and interstitial amyloid depositions. RAPS grade I, II and III were detected in 5.6%, 27.8% and 66.7% of the patients, respectively. Ten patients (55.5%) reached end-stage renal disease (ESRD) at a median time of 15 (IQR, 2.3-32.3) months post-biopsy. ESRD was correlated with interstitial fibrosis/tubular atrophy (r=0.608, P= 0.01). Death-censored renal survival rates at 1,3 and 5 years were 83.3%, 58.7% and 43.5%, respectively. Six patients (33.3%) died. Patient survival rates at 1,3 and 5 years were 88.9%, 69.6 and 55.7%, respectively. Conclusion: Early diagnosis of AA amyloidosis with renal biopsy and scoring biopsy specimen according to amyloid distribution with other histopathological findings may be useful to manage the disease and predict the prognosis. [ABSTRACT FROM AUTHOR]

Objective: The amount and distribution pattern of amyloid deposits may contribute to renal function and outcome, given the great diversity of renal involvement in amyloidosis. The aim of this study was to analyze the impact of histological characteristics of patients with biopsy-proven renal AA amyloidosis (AAA) on renal outcome. Methods: Renal biopsies of 37 patients with AAA were re-evaluated. The distribution pattern of glomerular amyloid (GA) deposits was classified, the extent of amyloid deposits in glomeruli, vessel, and interstitium and other histopathologic lesions were scored, and renal amyloid prognostic score (RAPS) was determined by summing all scores. Their potential prognostic relevance on renal outcome was investigated. Results: GA and vascular amyloid (VA) deposits were noted in all cases, interstitial amyloid (IA) was detected in 70.2%. GA deposits were predominantly seen in diffuse mesengiocapillary fashions (class IV) (51.4%). GA class, the extent of GA, VA, IA deposit, and RAPS, as well as interstitial fibrosis (IF) and interstitial inflammation were correlated to renal function at diagnosis. During the median follow-up of 52 months, 13 patients developed doubling of serum creatinine or end stage renal disease and they had a higher degree of GA and VA load (p = 0.03 and p = 0.042, respectively) as compared to the remaining patients. VA load, but not GA and RAPS grade, was associated with poor renal outcome (HR 3.016, 95% CI 1.45–6.25, p = 0.003). Conclusions: Baseline renal function is closely linked to the extent of AA amyloid deposit in renal parenchyma but only VA load was a predictor of renal outcome in AAA patients. [ABSTRACT FROM AUTHOR]

AA amyloidosis may complicate several chronic inflammatory conditions. From a clinical point of view, causality between inflammatory pathology and AA amyloidosis can be assumed because of the data described in the literature; some of the best known include rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, and chronic infections. Singles cases of inflammatory diseases have been found at AA amyloidosis. Causality becomes more plausible if at least two different cases with AA amyloidosis are both found to have the same rare inflammatory disease. We describe the case of a patient with primary sclerosing cholangitis (PSC) with development of AA amyloidosis conditioning a nephrotic syndrome, likely secondary to failure to control the chronic inflammatory process. Only two cases in the literature describe the association of this rare disease and the appearance of AA amyloidosis. The treatment of AA amyloidosis consists in treating the underlying inflammatory disorder; to date, few effective treatments are available for PSC. Therefore, and in view of the limited data in the literature, we believe it is important to describe its association. [ABSTRACT FROM AUTHOR]

Amyloidosis is a complex group of rare conditions. For patients, amyloidosis is severely debilitating: physically and psychologically. Currently, data are lacking to evaluate the medical, economic, and social burden of systemic amyloidosis. To analyse the patient burden according to the main types of systemic amyloidosis. The French Daily Impact of Amyloidosis study was an observational, cross-sectional and non-interventional study. Adults diagnosed with light chain (AL), transthyretin (ATTR), amyloid A (AA) and other rare forms of amyloidosis were eligible. Data regarding amyloidosis prevalence, diagnosis, management, and impact on everyday life were collected using a study-specific survey built by the Association Française Contre l'Amylose (AFCA) and the four French National Referral Centres for Amyloidosis. A total of 603 patients, predominantly male (65%) with an average age of 66.8 years, including 170 AL, 224 ATTRv, 109 ATTRwt and 25 AA amyloidosis patients, completed the study-specific survey. The median delay from presentation to confirmed diagnosis was 27.4 months but varied according to amyloidosis type. Patients before diagnosis had breathlessness (49%), tingling sensation (33%), pain (28%), difficulty in walking (28%) and weight loss (22%). Amyloidosis was most frequently suspected (49%) and confirmed (57%) in local hospitals but managed in French amyloidosis referral centres (58%). Patients often reported problems with mobility, usual activities, pain/discomfort and anxiety/depression, but not with self-care. Systemic amyloidosis severely impacts daily life. The delay to confirmed amyloidosis diagnosis needs to be reduced. Early, effective treatment is required to optimise patient benefits. [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF) is an autosomal recessive disorder, particularly common in the Mediterranean area. Mutations in the MEVF gene cause it. AA Amyloidosis is the most severe complication of FMF leading to chronic renal failure. We describe a rare pediatric case of a phenotype I familial Mediterranean fever with V726A heterozygous mutation. The diagnosis was made at chronic kidney disease. We discuss through this case the importance of the early diagnosis of FMF heterozygous children which is not usually evident in some phenotypes. It will surely avoid fatal complications, inappropriate therapeutic approaches and higher healthcare costs., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Polymyalgia rheumatica associated amyloidosis is an extremely rare condition that can be rapidly progressive with high morbidity and mortality and management is challenging. Tocilizumab is a monoclonal anti IL-6 receptor antibody which is in the therapeutic arsenal of polymyalgia rheumatica. The efficiency of tocilizumab in improvement of polymyalgia rheumatica activity score and decreasing steroid dose is well established, while efficiency in polymyalgia rheumatica associated amyloidosis has not been published. Herein, we reported a polymyalgia rheumatica patient with AA amyloidosis who was treated effectively with tocilizumab., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Increased plasma levels of serum amyloid A (SAA), an acute-phase protein that is secreted in response to inflammation, may lead to the accumulation of amyloid in various organs thereby obstructing their functions. Severe cases can lead to a systemic disorder called AA amyloidosis. Previous studies suggest that the N-terminal helix is the most amyloidogenic region of SAA. Moreover, computational studies implicated a significant role for Arg-1 and the residue-specific interactions formed during the fibrillization process. With a focus on the N-terminal region of helix-1, SAA 1-13 , mutational analysis was employed to interrogate the roles of the amino acid residues, Arg-1, Ser-5, Glu-9, and Asp-12. The truncated SAA 1-13 fragment was systematically modified by substituting the key residues with alanine or uncharged but structurally similar amino acids. We monitored the changes in the amyloidogenic propensities, associated conformational markers, and morphology of the amyloids resulting from the mutation of SAA 1-13 . Mutating out Arg-1 resulted in much reduced aggregation propensity and a lack of detectable β-structures alluding to the importance of salt-bridge interactions involving Arg-1. Our data revealed that by systematically mutating the key amino acid residues, we can modulate the amyloidogenic propensity and alter the time-dependent conformational variation of the peptide. When the behaviors of each mutant peptide were analyzed, they provided evidence consistent with the aggregation pathway predicted by MD simulation studies. Here, we detail the important temporal molecular interactions formed by Arg-1 with Ser-5, Glu-9, and Asp-12 and discuss its mechanistic implications on the self-assembly of the helix-1 region of SAA., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as interleukin-1β (IL-1β), TNF-α, and interleukin-6 (IL-6) inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented., Objective: To evaluate the efficacy and safety of tocilizumab in the treatment of FMF., Methods: Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF., Results: After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF., Conclusion: This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Serum amyloid A protein (AA) amyloidosis, also known as secondary amyloidosis, is a known consequence of chronic inflammation and results from several conditions including inflammatory arthritis, periodic fever syndromes, and chronic infection. AA amyloidosis can lead to multiorgan dysfunction, including changes in glomerular filtration rate and proteinuria. Definitive diagnosis requires tissue biopsy, and management of AA amyloid kidney disease is primarily focused on treating the underlying inflammatory condition to stabilize glomerular filtration rate, reduce proteinuria, and slow potential progression to kidney failure. In this narrative review, we describe the causes, pathophysiology, presentation, and pathologic diagnosis of AA amyloid kidney disease using an illustrative case of biopsy-proven AA amyloid kidney disease in a patient with long-standing rheumatoid arthritis who had a favorable response to interleukin 6 inhibition. We conclude the review with a description of established and more novel therapies for AA amyloidosis including published cases of use of tocilizumab (an interleukin 6 inhibitor) in biopsy-proven AA amyloid kidney disease.

We aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction, and oxidative stress in a cohort of familial Mediterranean fever (FMF) patients with Serum Amyloid A amyloidosis, in a non-randomized, 24-week open-label interventional study. Morinda citrifolia (anti-atherosclerotic-AAL), omega-3 (anti-inflammatory-AIC), and extract with Alaskan blueberry (antioxidant-AOL) were given to patients with FMF-related biopsy-proven AA amyloidosis. Patients were >18 years and had proteinuria (>3500 mg/day) but a normal estimated glomerular filtration rate (eGFR). Arterial flow-mediated dilatation (FMD), carotid intima media thickness (CIMT), and serum biomarkers asymmetric dimethylarginine (ADMA), high sensitivity C-reactive protein (hs-CRP), pentraxin (PTX3), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GSH-Px) were studied at baseline and after 24 weeks of treatment. A total of 67 FMF-related amyloidosis patients (52 male (77.6%); median age 36 years (range 21–66)) were enrolled. At the end of a 24-week treatment period with AAL, AIC, and AOL combination therapy, ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px, and FMD levels were significantly increased. Changes in inflammatory markers PTX3, and hsCRP were negatively correlated with FMD change, and positively correlated with decreases in proteinuria, ADMA, MDA, cholesterol, and CIMT. Treatment with AAL, AIC and AOL combination for 24 weeks were significantly associated with reduction in inflammatory markers, improved endothelial functions, and oxidative state. Efficient control of these three mechanisms can have long term cardiovascular and renal benefits for patients with AA amyloidosis. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains underestimated in familial Mediterranean fever-associated AA amyloidosis (FMF-AA). We aimed to compare early markers of endothelial dysfunction and atherosclerosis in FMF-AA with a homozygous M694V mutation (Group 1 = 76 patients) in the Mediterranean fever (MEFV) gene and in patients with other genotypes (Group 2 = 93 patients). Measures of increased risk for future CVD events and endothelial dysfunction, including flow-mediated dilatation (FMD), pentraxin-3 (PTX3), and carotid intima-media thickness (cIMT), and fibroblast growth factor 23 (FGF23) as a marker of atherosclerotic vascular disease were compared between groups. The frequency of clinical FMF manifestations did not differ between the two groups apart from arthritis (76.3% in Group 1 and 59.1% in Group 2, p < 0.05). FMD was significantly lower in Group 1 when compared with Group 2 (MD [95% CI]: −0.6 [(−0.89)–(−0.31)]). cIMT, FGF23, and PTX3 levels were higher in Group 1 (cIMT MD [95% CI]: 0.12 [0.08–0.16]; FGF23 MD [95% CI]: 12.8 [5.9–19.6]; PTX3 MD [95% CI]: 13.3 [8.9–17.5]). In patients with FMF-AA, M694V homozygosity is associated with lower FMD values and higher cIMT, FGF23, and PTX3 levels, suggesting increased CVD risk profiles. These data suggest that a genotype–phenotype association exists in terms of endothelial dysfunction and atherosclerosis in patients with FMF-AA. [ABSTRACT FROM AUTHOR]

Introduction: While light chain (AL) amyloidosis is more common in western countries, the most common type of amyloidosis is amyloid A (AA) amyloidosis in Eastern Mediterranean Region, including Turkey. Although worse prognosis has been attributed to the AL amyloidosis, AA amyloidosis can be related to higher mortality under renal replacement therapies. However, there are no sufficient data regarding etiology, clinical presentation, and prognostic factors of AA amyloidosis. The objective of our study is to evaluate the clinical, laboratory characteristics, and possible predictive factors related to mortality in patients with AA amyloidosis undergoing hemodialysis (HD). Methods: This multicenter, cross‐sectional study was a retrospective analysis of 2100 patients on HD. It was carried out in 14 selected HD centers throughout Turkey. Thirty‐two patients with biopsy‐proven AA amyloidosis and thirty‐two control patients without AA amyloidosis undergoing HD were included between October 2018 and October 2019. There was no significant difference between the groups in terms of age and dialysis vintage. Causes of AA amyloidosis, treatment (colchicine and/or anti‐interleukin 1 [IL] treatment), and the number of familial Mediterranean fever (FMF) attacks in the last year in case of FMF, systolic and diastolic blood pressures, biochemical values such as mean CRP, hemoglobin, serum albumin, phosphorus, calcium, PTH, ferritin, transferrin saturation, total cholesterol levels, EPO dose, erythropoietin‐stimulating agents resistance index, interdialytic fluid intake, body mass indexes, heparin dosage, UF volume, and Kt/V data in the last year were collected by retrospective review of medical records. Findings Prevalence of AA amyloidosis was found to be 1.87% in HD centers. In amyloidosis and control groups, 56% and 53% were male, mean age was 54 ± 11 and 53 ± 11 years, and mean dialysis vintage was 104 ± 94 and 107 ± 95 months, respectively. FMF was the most common cause of AA amyloidosis (59.5%). All FMF patients received colchicine and the mean colchicine dose was 0.70 ± 0.30 mg/day. 26.3% of FMF patients were unresponsive to colchicine and anti‐IL‐1 treatment was used in these patients. In AA amyloid and control groups, erythropoietin‐stimulating agents resistance index were 7.88 ± 3.78 and 5.41 ± 3.06 IU/kg/week/g/dl, respectively (p = 0.008). Additionally, higher CRP values (18.78 ± 18.74 and 10.61 ± 10.47 mg/L, p = 0.037), lower phosphorus (4.68 ± 0.73 vs. 5.25 ± 1.04 mg/dl, p = 0.014), total cholesterol (135 ± 42 vs. 174 ± 39 mg/dl, p < 0.01), and serum albumin (3.67 ± 0.49 mg/dl, 4.03 ± 0.22, p < 0.01) were observed in patients with AA amyloidosis compared to the control group. Discussion In this study, we found that long‐term prognostic factors including higher inflammation, malnutritional parameters, and higher erythropoietin‐stimulating agents resistance index were more frequent in AA amyloidosis patients under HD treatment. [ABSTRACT FROM AUTHOR]

More than 35 amyloid precursor proteins have been identified and many have tropism for the kidney. Renal amyloidosis is most commonly seen in AL and AA amyloidosis and the main clinical manifestations are proteinuria and progressive renal dysfunction. On renal pathology, hallmark findings of amyloidosis include Congo red positivity with apple-green birefringence and randomly arranged fibrils measuring 7-12 nm in diameter on ultrastructural examination. Management of renal amyloidosis typically combines therapy targeting the underlying amyloid process and supportive management. Patients with renal amyloidosis who progress to end-stage renal disease can be treated with dialysis, and in selected patients, with renal transplantation. [ABSTRACT FROM AUTHOR]

Familial Mediterranean fever (FMF), the most frequent monogenic autoinflammatory disease, is manifested with recurrent and chronic inflammation and amyloid A (AA) amyloidosis, driven by overproduction of interleukin 1 (IL-1) through an activated pyrin inflammasome. Consequently, non-responsiveness to colchicine, the cornerstone of FMF treatment, is nowadays addressed by IL-1- blockers. Each of the two IL-1 blockers currently used in FMF, anakinra and canakinumab, has its own merits for FMF care. Here we focus on anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, and explore the literature by using PubMed regarding the utility of anakinra in certain conditions of FMF. Occasionally we enrich published data with our own experience. To facilitate insights to anakinra role, the paper briefs some clinical, genetic, pathogenetic, and management aspects of FMF. The clinical settings of FMF covered in this review include colchicine resistance, AA amyloidosis, renal transplantation, protracted febrile myalgia, on- demand use, leg pain, arthritis, temporary suspension of colchicine, pediatric patients, and pregnancy and lactation. In many of these instances, either because of safety concerns or a necessity for only transient and short-term use, anakinra, due to its short half-life, is the preferred IL-1 blocker. [ABSTRACT FROM AUTHOR]

Les épidermolyses bulleuses dystrophiques récessives représentent un groupe de maladies génétiques, caractérisées par une fragilité cutanée et muqueuse, causées par des mutations dans le gène COL7A1. L'amylose AA constitue une complication rare de ces génodermatoses. Deux patients, porteurs d'une épidermolyse bulleuse dystrophique récessive, généralisée sévère dans le premier cas et généralisée intermédiaire dans le deuxième cas, ont développé à l'âge de 38 et 28 ans, respectivement, un syndrome néphrotique. Le diagnostic d'amylose rénale secondaire était confirmé par une biopsie rénale dans le premier cas et des glandes salivaires dans le deuxième cas. Le décès est survenu deux mois après dans les deux cas. L'amylose AA au cours des épidermolyses bulleuses dystrophiques récessives est souvent révélée par une atteinte rénale caractérisée par un syndrome néphrotique et une insuffisance rénale d'aggravation rapide. Le pronostic est sombre au vu de la fragilité du terrain et l'absence d'un traitement étiologique. Recessive dystrophic epidermolysis bullosa is a rare genetic condition characterized by fragile skin and mucous membrane, caused by mutations in the COL7A1 gene. AA amyloidosis is a rare complication of these genodermatosis. Two patients with recessive dystrophic epidermolysis bullosa, generalized severe in the first case and generalized intermediate in the second case, developed at the age of 38 and 28, respectively, nephrotic syndrome. The diagnosis of secondary renal amyloidosis was confirmed by renal biopsy in the first case and by minor salivary gland biopsy in the second case. Death occurred 2 months after diagnosis in both cases. Renal involvement is quite common in AA amyloidosis in patients with recessive dystrophic epidermolysis bullosa. Nephrotic syndrome and rapid decline in renal function renal are characteristic features. The prognosis is poor due to underlying conditions and the lack of an etiological treatment. [ABSTRACT FROM AUTHOR]

AA amyloidosis is a disease caused by extracellular deposition of insoluble β-pleated sheet fibrils composed of amyloid A (AA) protein, an amino (N)-terminal fragment of serum amyloid A (SAA). The deposits disrupt tissue structure and compromise organ function. Although the disease is systemic, deposition in kidney glomeruli is the most common manifestation. The leading cause of AA amyloidosis is sustained or recurrent inflammation accompanied by elevated levels of SAA. Factors determining the conversion of SAA to AA amyloid fibrils have yet to be fully resolved. Herein, we present liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis of AA proteins purified from eight patients with AA amyloidosis. For the first time, post-translational modifications (PTM), including carbamylation, acetylation and oxidation, were identified on AA peptides; all eight samples showed some degree of PTM. The amyloid in 6 samples comprised peptides derived from SAA1 with few or none from SAA2, while the other two samples contained both SAA1- and SAA2-derived peptides. N-terminal AA peptides beginning with Arg1 as well as AA peptides starting with Ser2 were present in five of the eight samples, while all or nearly all of the N-terminal peptides in the other three samples lacked Arg1. These data demonstrate that multiple species of AA amyloid proteins can comprise the subunits in amyloid fibrils and raise the possibility that PTM may play a role in fibrillogenesis. [ABSTRACT FROM AUTHOR]

Copyright of Nefrologia is the property of Revista Nefrologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Medical Journal of Ankara Training & Research Hospital is the property of Medical Journal of Ankara Training & Research Hospital and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)