Amyloid-Journal of Protein Folding Disorders最新文献

Background: ATTR is a systemic disease, causing significant morbidity and mortality, manifesting with symptoms affecting both the heart and nervous system. This study employed the Composite Autonomic Symptom Scale 31 (COMPASS-31) to assess autonomic symptoms in relation to ATTR-CM subtypes and the impact of dysfunction on prognosis.

Methods: This study included contemporary ATTR-CM patients enrolled in an institutional registry from 7/21-6/24. Demographic information, patient-reported outcomes (COMPASS-31 and Kansas City Cardiomyopathy Questionnaire (KCCQ)), 6-min walk test, and clinical data (hospitalisations, mortality) were collected and compared between ATTR-CM sub-types (ATTRwt, ATTRv-Val122Ile, ATTRv-non Val122Ile).

Results: 240 ATTR-CM patients (81% ATTRwt, 11% Val-122Ile, 8% non-Val122Ile) were studied. Following adjustment for age, significant COMPASS-31 score differences were observed between ATTRwt and ATTRv-nonV122I variant patients. "High" COMPASS-31 scores (≥35.42) were associated with later Columbia stage, lower exercise tolerance, and poorer quality of life (QOL) (all p < 0.05). Time-to-event analysis demonstrated higher probability of cardiovascular hospitalisations (CVH) for patients with "High" COMPASS-31 scores (p < 0.01). These patients also had increased CVH risk (HR = 4.26 [95% CI: 1.85-9.83], p = 0.001) independent of age, sex, ATTR type, Columbia Stage and diabetes.

Conclusions: Among ATTR-CM patients, autonomic dysfunction assessed via COMPASS-31 questionnaire was associated with more advanced disease stage and QOL impairment, and independently predicted CVH risk.

Objective: Amyloidosis is a group of disorders characterized by aggregation of abnormal amyloid protein in various tissues, often leading to organ dysfunction and failure. We optimized the immunogold electron microscopy (IEM) technique to enable efficient amyloid typing in 4% paraformaldehyde-fixed (PFA) and formalin-fixed paraffin-embedded (FFPE) tissues.

Methods: The optimized IEM technique was applied to 151 Congo-red positive specimens from various tissues representing different amyloidosis types; 117 were fixed in 4% PFA and 34 were FFPE samples. Specimens were embedded in Lowicryl/K4M and stained with modified Richardson's blue solution to differentiate amyloid (lavender-plum coloration stained) from non-amyloid (blue stained) areas under light microscopy. Antibodies against kappa and lambda light chains, transthyretin and amyloid A were used for amyloid typing by IEM.

Results: The optimized IEM technique enabled precise localization of amyloid deposits and rapid identification of target area under light microscopy for thin-section placement on nickel grids for immunogold staining. Of 151 specimens, 147 (97.4%) were classified as kappa or lambda light chains, transthyretin or amyloid A. Lambda light chain predominated in fat pad aspirates (56.8%), while transthyretin was most common in heart tissues (71.7%).

Conclusion: This optimized IEM technique enhances the accuracy and efficiency of amyloid typing, especially in samples with trace amyloid deposit. It offers significant advantages over traditional epoxy embedding with toluidine blue staining, supporting timely clinical diagnosis and therapeutic decision-making.

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are linked to immune-related adverse events (irAEs). Secondary (AA) amyloidosis, an inflammatory complication involving serum amyloid A deposition, has been sporadically reported in ICI-treated patients. We investigated the link between ICI therapy and AA amyloidosis using pharmacovigilance data and a systematic review.

Methods: We conducted a disproportionality analysis of FDA adverse event reporting system (FAERS) data (January 2015-June 2024), selecting amyloidosis-related cases using MedDRA preferred terms. Signal detection employed reporting odds ratio, proportional reporting ratio, information component, and empirical Bayesian geometric mean. We also reviewed published cases from six databases (searched 30 November 2024). Studies reporting AA amyloidosis linked to ICI use were included, and the risk of bias was assessed using the Joanna Briggs Institute tools. Results were summarised descriptively (PROSPERO ID: CRD42024622091).

Results: Among 13,209,688 unique FAERS reports, 26 relevant cases were identified. Patients were mainly older adults (median age 71.5 years), with serious outcomes including death (19.2%) and hospitalisation (30.8%). Disproportionality analyses showed a significant link, and the systematic review included 11 cases, primarily renal, with poor outcomes despite treatment.

Conclusion: Findings support AA amyloidosis as a rare but serious irAE of ICI therapy, warranting further investigation.

Background: AA amyloidosis is a rare but significant cause of chronic kidney disease (CKD). We aimed to characterize the clinical profile of patients with AA amyloidosis affecting the kidneys in the Indian subcontinent.

Methodology: In this retrospective cohort study, we evaluated patients with kidney biopsy-confirmed AA amyloidosis and compared them with a control group of patients with diabetic kidney disease (DKD). Primary outcome was defined as a composite of ≥50% decline in estimated glomerular filtration rate (eGFR) and/or progression to end-stage kidney disease (ESKD).

Results: AA amyloidosis (n = 91) accounted for 1.9% of all kidney biopsies. The median age was 45 years, and 75.8% were male. Chronic infections or inflammatory diseases were reported in 58.2%, tuberculosis being most common (35.2%). Baseline median eGFR was 66.0 mL/min/1.73 m² and urine protein creatinine ratio was 4.9 g/g. During median follow-up of 5.58 years, 38.6% experienced worsening kidney outcomes. Adjusted analyses showed significantly better kidney survival than DKD (0.29 (95% CI: 0.14-0.66, p = 0.002).

Conclusion: AA amyloidosis is an uncommon but important cause of CKD. Tuberculosis is the leading predisposing factor in Indian patients. These patients exhibit slower eGFR decline compared to DKD despite progressive proteinuria, suggesting distinct pathophysiology.