Search Results (186)

Cardiac amyloidosis (CA) results from the deposition of either immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid fibrils in the myocardium, causing restrictive cardiomyopathy and, if left untreated, can lead to early death. Advancements in non-invasive diagnostic modalities have led to an increased recognition of the disease. Monoclonal gammopathy plays a pivotal role in the diagnostic algorithm for CA, particularly in differentiating AL from ATTR. This review highlights the importance of monoclonal protein detection through serum protein electrophoresis, immunofixation electrophoresis, and serum free light chain assays as initial screening tools. However, these tests alone are insufficient for a definitive diagnosis due to the complexities associated with coexisting monoclonal gammopathies and the potential for false negative and positive results. Advanced imaging modalities, such as echocardiography, cardiac magnetic resonance, and nuclear scintigraphy, along with tissue biopsy, are crucial for confirming CA and accurately determining the CA subtype. Full article

Recombinantly produced monoclonal antibodies (mabs) belong to the fastest growing class of biotherapeutics. In humans, antibodies are classified into five different classes: IgA, IgD, IgE, IgG and IgM. Most of the therapeutic mabs used in the clinic belong to the IgG class, albeit other antibody classes, e.g., IgM, have been evaluated in clinical stages. Antibodies are composed of heavy chains paired with a light chain. In IgM and IgA, an additional chain, the J-chain, is present. Two types of light chains exist in humans: the κ-light chain and the λ-light chain. The κ-light chain predominates in humans and is used in the vast majority of therapeutic IgG. The reason for the preference of the κ-light chain in humans is not known. Our study investigates whether light-chain selection influences the productivity of the clinically validated mabs adalimumab and trastuzumab. Both mabs were expressed as IgG and IgM with a κ- or a λ-light chain in HEK293 cells. Besides comparing the expression levels of the different mabs, we also evaluated whether the passage number of the cell line has an impact on product yield. In addition, the expressions of adalimumab, trastuzumab, an anti-CD38 and an anti-PD-L1-antibody were analyzed in HEK293 and CHO cells when both the κ- and λ-light chains are present. In summary, IgG outperformed IgM variants in expression efficacy, while light-chain selection had minimal impact on the overall expression levels. The yields of all mab variants were higher in fresh cells, despite cell cultures with a high cell passage number having higher cell densities and cell numbers at the time of harvest. The incorporation of a particular light chain occurred at similar rates in HEK293 and CHO cells. Full article

Increasing evidence underlines the role of B-cells in the development of hepatic fibrogenesis following viral infections and metabolic dysfunction, through different mechanisms depending on the etiology. Circulating biomarkers of B-cell activation—such as B-cell activating factor (BAFF), immunoglobulin G (IgG) subclasses, and free light chains (FLCs)—may be associated with different results between viral and metabolic hepatic fibrosis, supporting their use as diagnostic tools. We conducted a case-control study including 100 patients with liver fibrosis, 50/100 of metabolic etiology and 50/100 of viral etiology. A reference group of 30 healthy donors was included as control. Serum levels of BAFF were measured using ELISA, while IgG subclasses (IgG1, IgG2, IgG3, IgG4), κ-FLC, λ-FLC, and the κ/λ ratio were quantified by turbidimetric methods. In univariate analysis, κ-FLC, λ-FLC, and BAFF levels were significantly elevated in both patient groups, with the highest concentrations consistently observed in metabolic fibrosis. IgG2 was selectively increased in metabolic fibrosis, whereas IgG3 was specifically elevated in viral fibrosis. Multivariate analysis confirmed these findings, showing a clear clustering of the three groups and identifying increased BAFF and κ-FLC as key features of metabolic fibrosis, while elevated IgG3 emerged as the most distinctive marker of viral etiology. These results reveal distinct B-cell-related immunological signatures in metabolic and viral hepatic fibrosis supporting the role of BAFF, FLCs, and IgG subclasses as biomarkers of etiological differentiation, and provide novel insights into the immune mechanisms driving fibrosis progression, potentially contributing to the identification of new therapeutic targets. Full article

Background/Objectives: Cardiac amyloidosis (CA) is an underdiagnosed and potentially life-threatening infiltrative cardiomyopathy characterized by the extracellular deposition of misfolded amyloid fibrils in cardiac tissue. It is most commonly associated with light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, either hereditary or wild-type. The disease often presents with non-specific symptoms, leading to delayed diagnosis and treatment. This study aims to provide a comprehensive overview of the pathophysiology, diagnostic strategies, and current therapeutic approaches for cardiac amyloidosis, with a focus on improving early detection and clinical outcomes. Methods: A narrative review was conducted using databases such as PubMed and Scopus, covering the period from September 2016 to March 2025. Keywords such as “cardiac amyloidosis”, “cardiac amyloidosis from transthyretin”, “cardiomyopathy”, “transthyretin”, “immunoglobulin light-chain amyloidosis”, and “familial amyloidosis” were used. Relevant clinical trials and guideline-based management recommendations were also included. Results: This review highlights that non-invasive imaging modalities and serum biomarker analyses are key to reducing diagnostic delays. New therapeutic developments, including gene-editing technologies and RNA-based therapies, show promise in early trials. Multidisciplinary management and increased awareness are crucial for timely diagnosis and treatment optimization. Conclusions: The early recognition of cardiac amyloidosis remains a major clinical challenge. Advances in non-invasive diagnostics and emerging disease-modifying therapies are transforming the prognosis of affected patients. Continued research and heightened clinical suspicion are essential to improve outcomes in this complex and heterogeneous disease. Full article

Background: Daratumumab-based regimens represent the gold-standard therapy for newly diagnosed AL amyloidosis patients. However, there are few studies about the efficacy of this treatment in real life. Methods: This study included 99 patients: 27 (27.3%) received daratumumab and proteasome inhibitor-based schemes, 46 (46.4%) were treated with proteasome inhibitors and/or immunomodulator-based regimens, and 26 (26.3%) were treated with chemotherapy. Results: Patients receiving daratumumab and proteasome inhibitor-based regimens achieved higher rates of partial haematological responses or better (100.0% vs. 78.3% vs. 58.3%; p = 0.009 and p < 0.001) and complete responses (74.1% vs. 37.0% vs. 12.5%; p = 0.003 and p < 0.001) than the proteasome inhibitors and/or immunomodulators and chemotherapy groups, respectively. Daratumumab and proteasome inhibitor-based schemes resulted in a shorter time to haematological response (1 month to partial response or better and 4 months to complete response). Moreover, in the group treated with daratumumab and proteasome inhibitor-based regimens, there was a trend of obtaining better and faster organ responses. The benefit of daratumumab and proteasome inhibitor-based regimens was that they resulted in an improvement in progression-free survival (not reached) compared to the proteasome inhibitor and chemotherapy groups (18 months; p = 0.022 and 6 months; p = 0.002). In addition, the clinical benefit was consistent in patients with Mayo Clinic stages III–IV. Conclusions: This study supports the efficacy and superiority of adding daratumumab to the frontline treatment over proteasome inhibitor-based regimens and chemotherapy in AL amyloidosis, including in advanced cardiac disease. Full article

Background: Cardiac amyloidosis (CA) is a progressive disorder characterized by amyloid fibril deposition in the heart, leading to heart failure and arrhythmias. Arterial stiffness, assessed by pulse wave velocity (PWV), is recognized as an adverse consequence of amyloidosis, yet its progression and relationship with myocardial dysfunction remain inadequately explored. This study examines the progression of PWV and its potential association with the deterioration of global longitudinal strain (GLS) in CA patients over a 6-month follow-up period. Methods: This prospective study enrolled 31 patients who were diagnosed with CA, including both the immunoglobulin light chain (AL) and transthyretin (ATTR) forms. All participants underwent a full echocardiographic study and PWV measurements (carotid-femoral [c-f] and carotid-radial [c-r] PWV) at baseline and 6-month follow-up. Age- and sex-matched individuals with similar cardiovascular risk factors were included as a control group. Results: In the CA group, the left ventricular mass index (LVMI) increased significantly from 119.4 ± 52.1 to 124 ± 53.2 g/m² (p = 0.002). Both c-f and c-r PWV showed significant increases at the 6-month follow-up (p < 0.001 and p = 0.005, respectively). The GLS deteriorated significantly from −14 ± 4.4% to −12.8 ± 4.9% (p = 0.018). No significant changes were observed in the control group. A weak correlation (r = 0.3; p = 0.095) was found between increases in PWV and GLS deterioration. Conclusions: Both arterial stiffness and myocardial dysfunction worsen rapidly in CA patients. However, the weak correlation between PWV and GLS suggests that they may evolve through independent mechanisms, necessitating further research to understand their complex interplay in CA. Full article

Background: A 69-year-old man with multiple myeloma and left-sided heart failure presented to the hospital with a two-month fever. Method: A transjugular liver biopsy was performed due to the rapid progression of liver failure. The procedure was complicated by an intraperitoneal hemorrhage. The bleeding was managed expectantly. Result: Significantly elevated serum bilirubin levels occurred on the 13th day after liver biopsy. Increasing serum bilirubin levels were observed until the patient’s death due to a biliovenous fistula at the liver biopsy site. Simultaneously, his slightly elevated liver enzymes returned to normal. The patient died 23 days after liver biopsy due to acute respiratory distress syndrome. Fistulous communication between the biliary tree and the hepatic venous system with subsequent bile leakage into the venous system (bilhemia) can lead to bile deposition in the lungs. Bile deposition in the lungs may potentiate and accelerate the development of diffuse alveolar damage with hyaline membranes. Conclusions: Lambda and kappa light chain deposition in the pulmonary alveoli in patients with multiple myeloma can mimic typical hyaline membranes. Full article

Shrimp are highly favored by consumers for their delicious taste and rich nutritional value. However, reports of allergic reactions caused by shrimp and its derivatives have been increasing, significantly impacting consumer health and posing a growing global food safety concern. This article introduces the structure and biochemical characteristics of major allergenic proteins in shrimp, including tropomyosin (TM), arginine kinase, sarcoplasmic calcium-binding protein, myosin light chain, troponin C, and hemocyanin. Currently, there is no effective treatment for shrimp allergies, and prevention is mainly achieved by avoiding consumption. The study of shrimp allergen sensitization reduction technology is of great significance to the development of hypoallergenic or desensitized products. The article provides a detailed overview of the effects of common processing techniques, including physical, chemical, biological, and combined methods, on the allergenicity of shrimp allergens; for instance, the binding rate to immunoglobulin E (IgE) was reduced by 73.59% after treating TM with high pressure (500 MPa) at 55 °C for 10 min and the recognition rate of TM to IgE decreased by 89.4% on average after treating TM with pepsin (30 μg/mL, pH 2) for 2 h. These techniques provide references for the development of hypoallergenic aquatic products or desensitized foods. Full article

Background/Objectives: Bence Jones proteins (BJPs) are monoclonal immunoglobulin free light chains (FLCs) that appear in the urine of patients with plasma cell disorders, including multiple myeloma (MM), Waldenström’s macroglobulinemia (WM), or light chain amyloidosis (AL). Their presence can provide valuable information about disease progression and treatment efficacy. These proteins are typically detected through a 24-h urine collection, as recommended by clinical guidelines. However, this method can be inconvenient for both patients and laboratory personnel due to its time-consuming nature and the potential for collection errors. We propose an algorithm based on serum FLC (sFLC) to rule out the presence of BJPs and diminish the need for urine testing. Methods: A retrospective data analysis of 268 serum and urine samples from 44 patients with MM was performed, and cutoffs were established to predict BJP absence: total urine protein (0.115 g/L), sFLC κ/λ ratio (>0.82 λ monoclonality and <1.99 κ monoclonality), and difference of involved–uninvolved FLC (dFLC; <11.93 mg/L). A subsequent algorithm validation was performed in 716 samples from patients who underwent the same testing in routine 2023 other laboratory activity. Results: The validation of these cutoffs to rule out the presence of BJP showed that, if the protocol based on the sFLC κ/λ ratio and dFLC had been applied, 42% of the urine studies would have been avoided, achieving a sensitivity of 93.9% and a false negative rate of 6.11%. Conclusions: We propose a laboratory work protocol that would allow for the avoidance of almost half of the 24-h urine studies based on sFLC measurement, a faster and more objective alternative to urine analysis for screening out the presence of BJP, with a good sensitivity and a low false negative rate. Full article

Background: Plasma cell myeloma is an incurable malignancy of clonal plasma cells. Recent success in immunotherapeutic strategies has altered the landscape of myeloma treatment. Daratumumab is an anti-CD38 IgG kappa monoclonal antibody that has shown great efficacy in the treatment of myeloma. However, Daratumumab brought with it new challenges in post-therapeutic laboratory assessment, including therapeutic antibody interference with serum protein electrophoresis and serum immunofixation electrophoresis assays. In this study, we highlight the interference identified in post-therapeutic flow cytometry analysis related to bound Daratumumab on normal hematopoietic cells. We also highlight the methods of detection of residual plasma cell neoplasm, post-Daratumumab therapy.: A total of 28 patients with refractory plasma cell myeloma who received Daratumumab (2016–2018) were included in this study. Flow cytometry was performed using 4- or 10-color antibody panels (BD FASC Canto) and analyzed by cluster analysis (Cytopaint Classic software) using four tube panels including VS38c for measurable residual disease (MRD) testing. Pretreatment and post-Daratumumab follow-up bone marrow flow cytometry samples were analyzed. In addition, 10 multiple myeloma patient samples were reflexed to multi-epitope CD38 analysis by flow cytometric analysis of post-Daratumumab residual disease. When discussing CD38 expression, we will refer to CD38 as being detected by conventional reagents. Results: All post-Daratumumab-treated cases (100%) showed negative staining for CD38 using conventional reagents on all plasma cells in the specimens. MRD testing successfully identified small clonal plasma cell populations using VS38C and multi-epitope CD38 (meCD38) antibodies, despite the absence of demonstrable CD38 expression. Additionally, all cases exhibited weak kappa light chain staining on hematogones, attributed to the binding of Daratumumab kappa monoclonal antibody. This interaction can create the appearance of a CD10+ monotypic B-cell population. We also noted diminished CD38 staining on myeloblasts, resulting in an atypical CD34/CD38 staining pattern. This alteration could potentially be misinterpreted as indicative of a myelodysplastic neoplasm (MDS). Furthermore, decreased staining of CD38 was noted on T cells, natural killer (NK) cells, basophils, monocytes, and plasmacytoid dendritic cells. Conclusions: With the emergence of successfully targeted immunotherapies, such as anti-CD38 antibodies, it is important to understand and correctly interpret variations in flow cytometry that may arise from the therapy. Hematogones exhibit high-intensity levels of CD38 expression; thus, Daratumumab binds to them, creating the appearance of kappa expression on all hematogones. Stage I/early stage II hematogones normally lack surface immunoglobulin light chain expression, but in the presence of Daratumumab, they appear to be a CD10(+) monotypic population of B cells. The misinterpretation of these normal cells as a CD10(+) B-cell clone can lead to inaccurate assessment, unnecessary bone marrow immunohistochemical evaluation, and unwarranted anxiety. Additionally, artefacts on various other hematopoietic cells can result in inaccurate assessments of immunophenotypic aberrancy due to binding of the drug. This may lead to the false interpretation of a secondary/therapy-related myeloid neoplasm. This study highlights in detail the interferences that must be considered when assessing residual disease in the era of targeted drug therapies. Full article

The prevalence of cardiac amyloidosis (CA), especially as a cause of heart failure, has significantly increased in recent years. Early detection and accurate assessment of the disease burden are crucial for initiating timely treatment and ensuring precise prognosis. CA primarily results from the infiltration of the myocardium by either immunoglobulin light chain fibrils (AL) or transthyretin fibrils (ATTR), leading to restrictive cardiomyopathy and eventual death if untreated. Over the past decade, advancements in diagnostic imaging and heightened clinical awareness have revealed a substantial presence of CA, particularly ATTR, among the elderly. These diagnostic improvements encompass echocardiography, cardiac computerized tomography scans, magnetic resonance imaging, and radionuclide scintigraphy with bone-avid tracers. Concurrently, significant progress has been made in therapeutic options, with new disease-modifying treatments now available that can dramatically alter the disease trajectory and improve survival rates when administered early. However, despite these advancements, there remains an urgent need for the early and accurate detection of CA to ensure that patients can fully benefit from these emerging therapies. Full article

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by recurrent eczema and chronic itching, affecting a significant portion of the global population. This study investigated the effects of Corydalis Tuber 70% ethanol extract (CTE) on tumor necrosis factor-α- and interferon-γ (TI)-stimulated human keratinocytes (HaCaT) and a house dust mite-induced AD mouse model, elucidating its mechanism via transcriptome analysis. A total of 13 compounds, including columbamine, corydaline, dehydrocorydaline, and glaucine, were identified in CTE using ultra performance liquid chromatography-tandem mass spectrometry. CTE downregulated pathways related to cytokine signaling and chemokine receptors in TI-stimulated HaCaT cells. It significantly inhibited C-C motif chemokine ligand (CCL)5, CCL17, and CCL22 levels by blocking the Janus kinase-signal transducers and activators of transcription and nuclear factor kappa-light-chain-enhancer of activated B cells pathways. In the AD mouse model, topical CTE significantly decreased dermatitis scores, epidermal thickening, and inflammatory cell infiltration. Plasma levels of histamine, immunoglobulin E, CCL17, CCL22, corticosterone, and cortisol were reduced. Lesions showed decreased thymic stromal lymphopoietin, CD4⁺ T cells, interleukin-4, and intercellular adhesion molecule-1 expression. The findings demonstrate that CTE alleviates AD by modulating inflammatory mediators, cytokines, and chemokines, reducing inflammatory cell infiltration, and alleviating stress-related factors. Full article

Background: A total of 50% of patients with AL amyloidosis have t(11;14) translocation, allowing us to use the selective oral BCL-2 inhibitor venetoclax in their treatment. Case presentation: Our patient was admitted to the gastroenterology department due to weight loss and abdominal pain. An abdominal CT scan revealed some enlarged lymph nodes; therefore, he was referred to the hematology department. A bone marrow biopsy showed massive amorphous amyloid deposition. The sample was positive on Congo red staining and exhibited double refraction under a polarized light microscope. Serum-free light chains and the difference between involved and uninvolved free light chains (dFLCs) were elevated. Using fluorescent in situ hybridization, we detected t(11;14) translocation. Further examinations confirmed the involvement of the liver, colon and heart. Stage II AL amyloidosis was confirmed. Our patient received combined induction therapy with CyBorD and venetoclax due to the presence of the t(11;14) translocation. After six cycles, the patient achieved complete remission. Autologous stem cell transplantation (ASCT) was performed. At 100 days post-ASCT, the patient had complete hematologic remission. Venetoclax maintenance treatment was initiated. The follow-up examinations showed that the patient is in very good partial remission. Conclusions: In the case of our AL amyloidosis patient with t(11;14) translocation, the combined treatment with CyBorD and venetoclax was well tolerated and effective. Full article

Amyloidosis is a rare pathology characterized by protein deposits in various organs and tissues. Cardiac amyloidosis (CA) can be caused by various protein deposits, but transthyretin amyloidosis (ATTR) and immunoglobulin light chain (AL) are the most frequent pathologies. Protein misfolding can be induced by several factors such as oxidative stress, genetic mutations, aging, chronic inflammation, and neoplastic disorders. In ATTR cardiomyopathy (ATTR-CM), the amyloid fibrils can be found in the myocardium interstitial space and are associated with arrhythmias and heart failure. In pathological situations, the transthyretin (TTR) configuration is destroyed by proteolytic action, leading to monomers that further misfold and aggregate to form the amyloid fibrils. ^99mTc-Pyrophosphate (^99m-Tc-PYP), ^99mTc 3,3-diphosphono-1,2-propanodicarboxylic acid (^99m-Tc-DPD) and ^99m-Tc hydroxy-methylene-Dyphosphonate (^99m-Tc-HMDP) are used to detect myocardium amyloid deposits due to their ability to detect calcium ions that are present in the amyloid fibrils through dystrophic calcification. ATTR-CM therapy acts on different stages of the amyloidogenic process, including liver TTR synthesis, TTR tetramer destabilization, and misfolding of the monomers. The main aim of this narrative review is to present ATTR-CM, starting with molecular changes regarding the protein misfolding process and radionuclide aspects and finishing with pharmacological approaches. Full article

Background/Objectives: Adenoviral vector-based vaccines against COVID-19 rarely cause vaccine-induced immune thrombocytopenia and thrombosis (VITT), a severe adverse reaction caused by IgG antibodies against platelet factor 4 (PF4). To study VITT, patient samples are crucial but have become a scarce resource. Recombinant antibodies (rAbs) derived from VITT patient characteristic amino acid sequences of anti-PF4 IgG are an alternative to study VITT pathophysiology. Methods: Amino acid sequences of the variable region of immunoglobulin light and heavy chain of anti-PF4 IgG derived from VITT patients were obtained by mass spectrometry sequencing and rAbs were synthetized by reverse-engineering. Six different rAbs were produced: CR23003, CR23004, and CR23005 (from a patient vaccinated with Jcovden, Johnson & Johnson-Janssen (Beerse, Belgium)), CR22046, and CR22050 and CR22066 (from two different patients vaccinated with Vaxzevria, AstraZeneca (Cambridge, UK)). These rAbs were further characterized using anti-PF4 and anti-PF4/heparin IgG ELISAs, rapid anti-PF4 and anti-PF4/polyanion chemiluminescence assays, and PF4-induced platelet activation assay (PIPA) and their capacity to induce procoagulant platelets. Results: rAbs bound to PF4 alone, but not to PF4/polyanion complexes in rapid chemiluminescence assays. Chemiluminescence assays and both anti-PF4 IgG and anti-PF4 IgG/heparin ELISA showed concentration-dependent PF4 binding of all six rAbs, however, with different reactivities among them. PIPA showed a similar, concentration-dependent platelet activation pattern. rAbs varied in their reactivity and the majority of the tested rAbs were able to induce procoagulant platelets. Conclusions: The six rAbs derived from VITT patients reflect VITT-typical binding capacities and the ability to activate platelets. Therefore, these rAbs offer an attractive new option to study VITT pathophysiology. Full article