An interesting case of AL amyloidosis and MM: a complex scenario with cardiac involvement.

Our patient presented with complaints of progressive shortness of breath for 1 month. She was diagnosed with a case of infiltrative type of restrictive cardiomyopathy (RCM) based on echocardiography and cardiac MRI findings. Her fat pad biopsy was suggestive of AL type of amyloidosis (AL). She was diagnosed with a case of multiple myeloma (MM) based on bone marrow biopsy findings with 48% plasma cells and a skeletal survey with lytic bone lesions on the skull, thus meeting the Crab criteria. We want to highlight the complex nature of this case and the difficulties associated with making a diagnosis. This case report presents an excellent opportunity to touch on the interesting topics of RCM, amyloidosis and MM.

Amyloidogenic light chains impair plasma cell survival.

Systemic light chain amyloidosis (AL) is a clonal plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains (LC) as insoluble fibrils in organs. The lack of suitable models has hindered the investigation of the disease mechanisms. Our aim was to establish AL LC-producing plasma cell lines and use them to investigate the biology of the amyloidogenic clone. We used lentiviral vectors to generate cell lines expressing LC from patients suffering from AL amyloidosis. The AL LC-producing cell lines showed a significant decrease in proliferation, cell cycle arrest, and an increase in apoptosis and autophagy as compared with the multiple myeloma LC-producing cells. According to the results of RNA sequencing the AL LC-producing lines showed higher mitochondrial oxidative stress, and decreased activity of the Myc and cholesterol pathways. The neoplastic behavior of plasma cells is altered by the constitutive expression of amyloidogenic LC causing intracellular toxicity. This observation may explain the disparity in the malignant behavior of the amyloid clone compared to the myeloma clone. These findings should enable future in vitro studies and help delineate the unique cellular pathways of AL, thus expediting the development of specific treatments for patients with this disorder.

Tracking Multiorgan Treatment Response in Systemic AL-Amyloidosis With Cardiac Magnetic Resonance Derived Extracellular Volume Mapping.

BACKGROUND: Systemic light chain amyloidosis is a multisystem disorder that commonly involves the heart, liver, and spleen. Cardiac magnetic resonance with extracellular volume (ECV) mapping provides a surrogate measure of the myocardial, liver, and spleen amyloid burden. OBJECTIVES: The purpose of this study was to assess multiorgan response to treatment using ECV mapping, and assess the association between multiorgan treatment response and prognosis. METHODS: The authors identified 351 patients who underwent baseline serum amyloid-P-component (SAP) scintigraphy and cardiac magnetic resonance at diagnosis, of which 171 had follow-up imaging. RESULTS: At diagnosis, ECV mapping demonstrated that 304 (87%) had cardiac involvement, 114 (33%) significant hepatic involvement, and 147 (42%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial HR: 1.03 [95% CI: 1.01-1.06]; P = 0.009; liver HR: 1.03; [95% CI: 1.01-1.05]; P = 0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R = 0.751; P < 0.001; R = 0.765; P < 0.001, respectively). Serial measurements demonstrated ECV correctly identified changes in liver and spleen amyloid load derived from SAP scintigraphy in 85% and 82% of cases, respectively. At 6 months, more patients with a good hematologic response had liver (30%) and spleen (36%) ECV regression than myocardial regression (5%). By 12 months, more patients with a good response demonstrated myocardial regression (heart 32%, liver 30%, spleen 36%). Myocardial regression was associated with reduced median N-terminal pro-brain natriuretic peptide (P < 0.001), and liver regression with reduced median alkaline phosphatase (P = 0.001). Changes in myocardial and liver ECV, 6 months after initiating chemotherapy, independently predict mortality (myocardial HR: 1.11 [95% CI: 1.02-1.20]; P = 0.011; liver HR: 1.07 [95% CI: 1.01-1.13]; P = 0.014). CONCLUSIONS: Multiorgan ECV quantification accurately tracks treatment response and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. Baseline myocardial and liver ECV and changes at 6 months independently predict mortality, even after adjusting for traditional predictors of prognosis.

Multi-Imaging Characterization of Cardiac Phenotype in Different Types of Amyloidosis.

BACKGROUND: Bone scintigraphy is extremely valuable when assessing patients with suspected cardiac amyloidosis (CA), but the clinical significance and associated phenotype of different degrees of cardiac uptake across different types is yet to be defined. OBJECTIVES: This study sought to define the phenotypes of patients with varying degrees of cardiac uptake on bone scintigraphy, across multiple types of systemic amyloidosis, using extensive characterization comprising biomarkers as well as echocardiographic and cardiac magnetic resonance (CMR) imaging. METHODS: A total of 296 patients (117 with immunoglobulin light-chain amyloidosis [AL], 165 with transthyretin amyloidosis [ATTR], 7 with apolipoprotein AI amyloidosis [AApoAI], and 7 with apolipoprotein AIV amyloidosis [AApoAIV]) underwent deep characterization of their cardiac phenotype. RESULTS: AL patients with grade 0 myocardial radiotracer uptake spanned the spectrum of CMR findings from no CA to characteristic CA, whereas AL patients with grades 1 to 3 always produced characteristic CMR features. In ATTR, the CA burden strongly correlated with myocardial tracer uptake, except in Ser77Tyr. AApoAI presented with grade 0 or 1 and disproportionate right-sided involvement. AApoAIV always presented with grade 0 and characteristic CA. AL grade 1 patients (n = 48; 100%) had characteristic CA, whereas only ATTR grade 1 patients with Ser77Tyr had characteristic CA on CMR (n = 5; 11.4%). After exclusion of Ser77Tyr, AApoAI, and AApoAIV, CMR showing characteristic CA or an extracellular volume of >0.40 in patients with grade 0 to 1 cardiac uptake had a sensitivity and specificity of 100% for AL. CONCLUSIONS: There is a wide variation in cardiac phenotype between different amyloidosis types across different degrees of cardiac uptake. The combination of CMR and bone scintigraphy can help to define the diagnostic differentials and the clinical phenotype in each individual patient.

Immunoglobulin Light Chain Amyloidosis Presenting as Inferior Vena Cava Thrombosis.

Immunoglobulin light chain (AL) amyloidosis is a rare disease characterized by the deposition of misfolded extracellular proteins within various body tissues resulting in dysfunction of the cardiac, renal, gastrointestinal, hematologic, and nervous systems, among others. Systemic AL amyloidosis often presents with a constellation of vague symptoms such as fatigue, dyspnea, and abdominal pain. Untreated AL amyloidosis with cardiac involvement is rapidly fatal with a median survival of 6 months. In this report, we will highlight the case of a 43-year-old female who presented with generalized abdominal symptoms and fatigue. She was found to have extensive inferior vena cava (IVC) thrombosis extending into the renal veins bilaterally in the setting of nephrotic range proteinuria, new onset arrhythmia, diastolic heart failure, gastrointestinal, and autonomic dysfunction. She received systemic thrombolytic therapy for the IVC and renal vein thrombosis. The multiorgan involvement led us to consider the possibility of amyloidosis. Abdominal fat pad biopsy was performed as part of the diagnostic effort. The abdominal fat pad biopsy did not reveal AL amyloidosis. Ultimately, the diagnosis of systemic AL amyloidosis was made on the basis of pathology from luminal biopsies obtained during outpatient esophagogastroduodenoscopy that was performed days prior to her admission. Unique to our case is the patient presentation with extensive thrombotic disease of the IVC and renal veins. It is important to understand the disease process, presenting signs and symptoms as well as diagnostic essentials based on current literature in order to minimize the morbidity and mortality of this rare disease.

A rare case of intramuscular orbital amyloidosis presenting as progressive esotropia in an adult.

Orbital amyloidosis is an uncommon entity. Lacrimal gland, orbital soft tissue and extraocular muscles are the usual sites of involvement. Deposition of amyloid in the extraocular muscle can be either isolated or associated with systemic amyloidosis. We describe a case of a 43-year-old male with isolated amyloid infiltration of the right lateral rectus muscle presenting as a progressive esotropia. The case was initially misdiagnosed as lateral rectus palsy and myositis due to non-specific radiological features of the entity. The diagnosis was confirmed by a biopsy. Intramuscular Botulinum toxin injection, was administered to the right medial rectus to alleviate diplopia temporarily, and strabismus surgery was planned at a later stage. Amyloid deposition is a rare cause of extraocular muscle enlargement. Histopathology is confirmatory. Screening for systemic amyloidosis is mandatory in all cases.

Renal AA amyloidosis: presentation, diagnosis, and current therapeutic options: a review.

Amyloid A amyloidosis is thought to be the second most common form of systemic amyloidosis behind amyloidosis secondary to monoclonal Ig. It is the result of deposition of insoluble fibrils in the extracellular space of tissues and organs derived from the precursor protein serum amyloid A, an acute phase reactant synthesized excessively in the setting of chronic inflammation. The kidney is the most frequent organ involved. Most patients present with proteinuria and kidney failure. The diagnosis is made through tissue biopsy with involvement of the glomeruli in most cases, but also often of the vessels and the tubulointerstitial compartment. The treatment usually targets the underlying etiology and consists increasingly of blocking the inflammatory cascade of cytokines with interleukin-1 inhibitors, interleukin-6 inhibitors, and tumor necrosis factor-α inhibitors to reduce serum amyloid A protein formation. This strategy has also shown efficacy in cases where an underlying etiology cannot be readily identified and has significantly improved the prognosis of this entity. In addition, there has been increased interest at developing effective therapies able to clear amyloid deposits from tissues, albeit with mitigated results so far.

Multiple myeloma initially manifesting as a solitary deep ulcer on the tongue: a case study and literature review.

Multiple myeloma (MM) is a malignant disease associated with clonal plasma cell proliferative disorder, characterized by extensive infiltration of clonal plasma cells in the bone marrow, for which a proportion of patients suffer poor outcome and exhibit no obvious symptoms in the early stages. Amyloidosis is a rare condition caused by MM. Immunoglobulin light chain amyloidosis (AL) is caused by the secretion of specific toxic light chain proteins from proliferating clonal B cells or plasma cells. These light chain proteins accumulate in human tissues and cause organ dysfunction and failure. Oral manifestations of amyloidosis include macroglossia, prominent lingual margins, coloured papules, purpura, and nodular protrusions. To describe and summarize the oral manifestations associated with AL amyloidosis in order to achieve an accurate clinical diagnosis. We present a case of AL amyloidosis associated with multiple myeloma and review the literature on other related cases identified from the inception of Medline. A female patient visited our clinic with a deep tongue ulcer. After oral biopsy and tissue staining, combined with the examination results from the Department of Haematology, the patient was diagnosed with oral AL amyloidosis related to multiple myeloma. This is the first case study of AL amyloidosis secondary to latent MM presenting as a solitary tongue ulcer. Chronic oral refractory ulcers may be associated with systemic diseases and should be considered in future clinical practice.

Amyloidosis in the nasopharynx and larynx: a case report.

Amyloidosis is a disease caused by amyloid deposition in tissues or organs. According to the extent of the lesion, it can be divided into systemic amyloidosis and localized amyloidosis. Amyloidosis originating in the larynx accounts for approximately 0.5% to 1.0% of benign lesions of the larynx; such lesions are relatively rare and mostly localized. Nasopharyngeal amyloidosis combined with laryngeal amyloidosis is even rarer. We herein present a case involving a patient with amyloidosis in the nasopharynx and larynx who presented with a foreign body sensation and hoarseness in the pharynx. Electronic fiber laryngoscopy revealed a smooth neoplasm in the left nasopharynx and left vocal cord. The patient underwent surgical treatment, and the postoperative pathologic examination results suggested amyloidosis. Special staining performed using Congo red and crystal violet was positive, confirming amyloidosis. The patient recovered after surgery, and no recurrence was present at the 3- and 6-month follow-ups.

A multidisciplinary case report of multiple myeloma with renal and cardiac involvement: a look beyond amyloidosis.

BACKGROUND: Multiple myeloma (MM) is a malignant neoplasm associated with kidney involvement in nearly half of the patients. Cast nephropathy, monoclonal immunoglobulin deposition disease (MIDD), and light chain (AL) amyloidosis are the most common monoclonal immunoglobulin-mediated causes of renal injury. Cardiac involvement is also present in MM, characterized by restrictive cardiomyopathy generated by light chain deposit or amyloid. Thromboembolic complications such as deep vein thrombosis or pulmonary embolism are also described. CASE PRESENTATION: We present an unusual multidisciplinary case of a woman with a newly diagnosed MM associated with severe proteinuria and high natriuretic peptide. A renal and fat pad biopsy with Congo red staining were performed but amyloid deposition was not discovered. While immunofluorescence on fresh frozen unfixed tissue was not contributory, the immunofluorescence on fixed tissue and electron microscopy revealed the correct diagnosis. During subsequent investigations, two intracardiac right-sided masses and massive pulmonary embolism were also detected. CONCLUSIONS: This case highlights that multiple organ involvement in patients with MM may result from a combination of paraprotein-dependent and -independent factors. Moreover, renal diseases induced by monoclonal gammopathies are a group of complex and heterogeneous disorders. Their subtle presentation and their potential multiorgan involvement require the expertise of a multidisciplinary team able to provide the most appropriate diagnostic and therapeutic assessment.

Imaging-Guided Treatment for Cardiac Amyloidosis.

PURPOSE OF REVIEW: This review will explore the role of cardiac imaging in guiding treatment in the two most commonly encountered subtypes of cardiac amyloidosis (immunoglobulin light-chain amyloidosis [AL] and transthyretin amyloidosis [ATTR]). RECENT FINDINGS: Advances in multi-parametric cardiac imaging involving a combination of bone scintigraphy, echocardiography and cardiac magnetic resonance imaging have resulted in earlier diagnosis and initiation of treatment, while the evolution of techniques such as longitudinal strain and extracellular volume quantification allow clinicians to track individuals' response to treatment. Imaging developments have led to a deeper understanding of the disease process and treatment mechanisms, which in combination result in improved patient outcomes. The rapidly expanding treatment regimens for cardiac amyloidosis have led to an even greater reliance on cardiac imaging to help establish an accurate diagnosis, monitor treatment response and aid the adjustment of treatment strategies accordingly.

Value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission: a case report and literature review.

BACKGROUNDS: Published literatures on repeat renal biopsy of AL amyloidosis have basically reached a consensus that amyloid material deposit does not disappear or diminish after satisfactory hematologic response, regardless of renal response. However, the need of a repeat renal biopsy in such situation is still controversial. CASE PRESENTATION: Here we reported a case of histologically confirmed λ Type renal AL amyloidosis who had been classified as Stage I and low risk at initial diagnosis. The patient received a total of six courses of CyBorD chemotherapy. She had achieved complete hematologic remission after two courses of chemotherapy but consistently had large amount of proteinuria over 10 g/day during follow up. A repeat renal biopsy was performed nine months after the first one and indicated mild to moderate increase of amyloid deposits as well as significant glomerulosclerosis and interstitial lesions, suggesting a lack of histological renal improvement despite her satisfactory hematologic response. CONCLUSIONS: This case indicated renal involvement in AL amyloidosis could progress after successful hematologic treatment, and supported the value of repeat renal biopsy in the evaluation of AL amyloidosis patients lacking renal response despite of complete hematologic remission.

Myocardial Composition in Light-Chain Cardiac Amyloidosis More Than 1 Year After Successful Therapy.

OBJECTIVES: The goals of this study were to characterize myocardial composition during the active and remission phases of light-chain (AL) cardiac amyloidosis. BACKGROUND: Cardiac dysfunction in AL amyloidosis is characterized by dual insults to the myocardium from infiltration and toxicity from light chains during the active phase and by infiltration alone in the remission phase. METHODS: Prospectively enrolled subjects with cardiac AL amyloidosis (21 remission AL amyloidosis; age: 63.4 ± 7.3 years; 47.6% male; and 48 active AL amyloidosis; age: 62.5 ± 7.4 years; 60.4% male) underwent contrast-enhanced cardiac magnetic resonance with T1 and T2 mapping and measurement of extracellular volume (ECV). By definition, serum free light-chain levels were normal for at least 1 year following successful AL therapy in the remission group and abnormal in the active group. RESULTS: Myocardial ECV was similarly expanded in the remission and active AL amyloidosis groups (0.488 ± 0.082 vs 0.519 ± 0.083, respectively; P = 0.15). However, myocardial T2 relaxation times (47.7 ± 3.2 ms vs 45.5 ± 3.0 ms; P = 0.008) as well as native T1 times (1,368 ms [IQR: 1,290-1,422 ms] vs 1,264 ms [IQR: 1,203-1,380 ms]; P = 0.024) were significantly higher in the remission compared to the active AL amyloidosis group. CONCLUSIONS: Myocardial ECV is substantially expanded in the active AL and remission AL cardiac amyloidosis groups, but native T1 values were higher, suggesting a different myocardial composition. There is no evidence of myocardial edema in active AL cardiac amyloidosis. Future phenotyping studies of AL cardiac amyloidosis need to consider complementary myocardial markers that define the interstitial milieu in addition to changes in extracellular volume. (Molecular Imaging of Primary Amyloid Cardiomyopathy; NCT02641145).

A randomized phase 3 study of ixazomib-dexamethasone versus physician's choice in relapsed or refractory AL amyloidosis.

In the first phase 3 study in relapsed/refractory AL amyloidosis (TOURMALINE-AL1 NCT01659658), 168 patients with relapsed/refractory AL amyloidosis after 1-2 prior lines were randomized to ixazomib (4 mg, days 1, 8, 15) plus dexamethasone (20 mg, days 1, 8, 15, 22; n = 85) or physician's choice (dexamethasone ± melphalan, cyclophosphamide, thalidomide, or lenalidomide; n = 83) in 28-day cycles until progression or toxicity. Primary endpoints were hematologic response rate and 2-year vital organ deterioration or mortality rate. Only the first primary endpoint was formally tested at this interim analysis. Best hematologic response rate was 53% with ixazomib-dexamethasone vs 51% with physician's choice (p = 0.76). Complete response rate was 26 vs 18% (p = 0.22). Median time to vital organ deterioration or mortality was 34.8 vs 26.1 months (hazard ratio 0.53; 95% CI, 0.32-0.87; p = 0.01). Median treatment duration was 11.7 vs 5.0 months. Adverse events of clinical importance included diarrhea (34 vs 30%), rash (33 vs 20%), cardiac arrhythmias (26 vs 15%), nausea (24 vs 14%). Despite not meeting the first primary endpoint, all time-to-event data favored ixazomib-dexamethasone. These results are clinically relevant to this relapsed/refractory patient population with no approved treatment options.

AL amyloidosis: untangling new therapies.

Systemic light chain (AL) amyloidosis is a protein misfolding disorder characterized by the deposition of abnormal immunoglobulin light chains in fibrillary aggregates, resulting in end-organ damage. Several unique challenges face treating physicians, including delayed diagnosis, advanced vital organ involvement, and morbidity with treatment. Aggressive supportive care and risk-adapted application of plasma cell-directed therapies are the cornerstones of management. The therapeutic revolution in multiple myeloma will likely further expand the arsenal against plasma cells. Careful investigation of these agents will be critical to establish their role in this fragile population. The promise of fibril-directed therapies to restore organ function remains despite early disappointments. In this review, we discuss new therapies to tackle AL amyloidosis using a case-based approach.

Pathological review of cardiac amyloidosis using autopsy cases in a single Japanese institution.

AIM: Amyloidosis is a systemic or localized disease of protein deposition characterized by amorphous eosinophilic morphology and positivity of Congo Red staining. The typing of amyloidosis is becoming increasingly important because therapeutic agents for each amyloidosis type have been developed. Herein, the authors review the autopsy cases at an institution to reveal the putative Japanese characteristics of each amyloidosis type and evaluate the clinicopathological significance of each type. MATERIALS AND METHODS: A total of 131 autopsy cases of systemic and localized amyloidosis were retrieved for classification by immunohistochemistry. Immunohistochemistry for transthyretin, amyloid A (AA), immunoglobulin light-chain kappa and lambda, and ß2-microglobulin was performed for all cases. RESULTS: The 131 amyloidosis cases were classified as follows: 71 cases (54.2%) of transthyretin amyloidosis, 32 cases (24.4%) of AA amyloidosis, 8 cases (6.1%) of light-chain amyloidosis, and 5 cases (3.8%) of ß2-microglobulin amyloidosis, along with 15 equivocal cases (11.5%). All cases showed myocardial involvement of amyloidosis. Histopathologically, the transthyretin type was significantly associated with the interstitial and nodular patterns, and with the absence of the perivascular and endocardial patterns. The AA type was significantly associated with the perivascular and endocardial patterns, and with the absence of the nodular pattern. CONCLUSION: The authors revealed the putative characteristics of cardiac amyloidosis in Japan by using autopsy cases. About 90% of amyloidosis cases were successfully classified using only commercially available antibodies.

Clinical and prognostic implications of capillary density in patients with cardiac light chain amyloidosis.

AIMS: Cardiac involvement is crucial factor determining outcomes of light chain (AL) amyloidosis. This study evaluated whether capillary density (CD) quantified from endomyocardial biopsy is associated with structural and functional parameters of amyloid heart. Also, we investigated whether capillary density improves the prognostic value of the current staging system in AL amyloidosis patients with cardiac involvement. METHODS AND RESULTS: A total of 67 patients with biopsy-proven AL cardiac amyloidosis were prospectively enrolled in this study. All patients underwent transthoracic echocardiography and EBM at the time of diagnosis. Left ventricle global longitudinal strain was evaluated on two-dimensional strain echocardiography. The primary endpoint was all-cause mortality. Amyloid load and capillary density were calculated on endomyocardial biopsy stained immunohistochemically with antibody against amyloid P and CD31, respectively. Among the study population, 37 patients (55.2%) were classified as Stage IV, and the cumulative incidence of death at 1 year was 34% (23 patients). A total of 65 (97%) patients underwent chemotherapy. CD showed a significant correlation with left ventricle global longitudinal strain (r = 0.274, P = 0.025), log N-terminal pro-B type natriuretic peptide (r = -0.311, P = 0.005), and amyloid load (r = -0.438, P < 0.001). Patients with a CD ≤ 220/mm2 were at significantly higher risk of death than those with a CD > 220/mm2 (P = 0.026 by log-rank test). A model based on the 2012 Mayo staging system and CD showed significantly better discrimination and reclassification ability than a model using the 2012 Mayo staging system alone (C-index 0.582 vs.0.689, P for difference <0.001). CONCLUSIONS: Capillary density was significantly related to the severity of amyloid deposits in the myocardium and showed incremental prognostic value in addition to the 2012 Mayo staging system.

The Ultrastructure of Tissue Damage by Amyloid Fibrils.

Amyloidosis is a group of diseases that includes Alzheimer's disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure of tissue damage resulting from amyloid deposition and therapeutic insights based on the pathophysiology of amyloidosis. Studies of nerve biopsy or cardiac autopsy specimens from patients with ATTR and AL amyloidoses show atrophy of cells near amyloid fibril aggregates. In addition to the stress or toxicity attributable to amyloid fibrils themselves, the toxicity of non-fibrillar states of amyloidogenic proteins, particularly oligomers, may also participate in the mechanisms of tissue damage. The obscuration of the basement and cytoplasmic membranes of cells near amyloid fibrils attributable to an affinity of components constituting these membranes to those of amyloid fibrils may also play an important role in tissue damage. Possible major therapeutic strategies based on pathophysiology of amyloidosis consist of the following: (1) reducing or preventing the production of causative proteins; (2) preventing the causative proteins from participating in the process of amyloid fibril formation; and/or (3) eliminating already-deposited amyloid fibrils. As the development of novel disease-modifying therapies such as short interfering RNA, antisense oligonucleotide, and monoclonal antibodies is remarkable, early diagnosis and appropriate selection of treatment is becoming more and more important for patients with amyloidosis.

Exploring the sequence features determining amyloidosis in human antibody light chains.

The light chain (AL) amyloidosis is caused by the aggregation of light chain of antibodies into amyloid fibrils. There are plenty of computational resources available for the prediction of short aggregation-prone regions within proteins. However, it is still a challenging task to predict the amyloidogenic nature of the whole protein using sequence/structure information. In the case of antibody light chains, common architecture and known binding sites can provide vital information for the prediction of amyloidogenicity at physiological conditions. Here, in this work, we have compared classical sequence-based, aggregation-related features (such as hydrophobicity, presence of gatekeeper residues, disorderness, ß-propensity, etc.) calculated for the CDR, FR or VL regions of amyloidogenic and non-amyloidogenic antibody light chains and implemented the insights gained in a machine learning-based webserver called "VLAmY-Pred" ( https://web.iitm.ac.in/bioinfo2/vlamy-pred/ ). The model shows prediction accuracy of 79.7% (sensitivity: 78.7% and specificity: 79.9%) with a ROC value of 0.88 on a dataset of 1828 variable region sequences of the antibody light chains. This model will be helpful towards improved prognosis for patients that may likely suffer from diseases caused by light chain amyloidosis, understanding origins of aggregation in antibody-based biotherapeutics, large-scale in-silico analysis of antibody sequences generated by next generation sequencing, and finally towards rational engineering of aggregation resistant antibodies.