Heart Function In Systemic and Localized AL Amyloidosis: Role of NT-ProBNP and MPC-1

Abstract Abstract 5006 In AL amyloidosis typical sites of amyloid buildup are heart, skin, gastrointestinal tract, liver, kidneys, and blood vessels. To evaluate the heart involvement in systemic and localized amyloidosis proBNP, peptide (NT-proBNP; 76 amino acids) and MPC-1 were investigated. NT-proBNP have been described as useful marker for the diagnosis heart disease, and its plasma concentrations correlate with the functional classification of patients according to the New York Heart Association (NYHA). MCP-1 is a chemokine that activates mononuclear phagocytes by promoting leukocyte–endothelium binding and migration to sites of inflammation. The MCP-1 levels seem to be related to the severity of cardiac alteration, as demonstrated by the coronary angiogram. NT-proBNP and MPC-1 serum levels were performed in systemic or localized AL amyloidosis to evaluate if there was a difference in the heart involvement. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. To analyze the results of NT-proBNP and MPC-1, Mann-Whitney test was performed. NT-proBNP serum values were significantly (p=0.007) increased in systemic disease. Also, MPC-1 serum levels were significantly (p=0.004) higher in the patients with systemic disease (350.52±58.70 pg/ml) if compared to the group of localized amyloidosis (147.82±26.03 pg/ml). On the basis of our results, the heart seem to be functionally more involved in AL systemic amyloidosis than in localized disease, as demonstrated by the higher NT-proBNP and MPC-1 serum values. Disclosures: No relevant conflicts of interest to declare.

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Valuation of MCP-1 and VEGF Chemokines In Serum of Patients with AL Amyloidosis

Blood ◽

10.1182/blood.v116.21.1922.1922 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1922-1922

Author(s):

Alessandro Moscetti ◽

Francesca Saltarelli ◽

Maria Paola Bianchi ◽

Guglielmo Bruno ◽

Gerardo Salerno ◽

...

Keyword(s):

Bone Marrow ◽

Inflammatory Process ◽

Conflicts Of Interest ◽

Systemic Disease ◽

Inflammatory Cells ◽

Mononuclear Phagocytes ◽

Systemic Amyloidosis ◽

Light Chains ◽

Al Amyloidosis ◽

Localized Amyloidosis

Abstract Abstract 1922 AL amyloidosis is a pathology characterised by the deposition of fibrillary aggregates of immunoglobuline light chains with β-sheet conformation. The light chains are synthetized by neoplastic plasma cell and fibrils deposition can infiltrate tissues leading to multi systemic organ damage. To evaluate if vascular modifications are involved in AL amyloidosis, inflammatory activity of cytokines as MCP-1 and VEGF was investigated. MCP-1 is a chemokine that activates mononuclear phagocytes by promoting leukocyte-endothelium binding and migration to sites of inflammation, while VEGF is an endothelial cell mitogen and permeability factor that is potently angiogenic in bone marrow of AL amyloidosis patients. Aim of this study is to evaluate serum cytokines MCP-1 and VEGF levels in patients with systemic or localized AL amyloidosis at presentation to find out potential differences useful to define a characteristic inflammatory pattern. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis and analyzed for serum MCP-1 and VEGF levels. Mann-Whitney test and Spearman correlation were used to compare results. MCP-1 level was significantly higher in the serum of patients with systemic disease (350.52±58.70 pg/ml) compared to the group of patients with localized amyloidosis (147.82±26.03; p=0.004); VEGF was also significantly increased in systemic disease group (p= 0.028). In addition, a positive correlation between MCP-1 and VEGF (r2= 0.755; p=0.031) has been found in the group of patients with systemic amyloidosis. Results seems to suggest a difference in serum cytokine MCP-1 and VEGF levels between AL systemic and localized amyloidosis. In systemic amyloidosis the neoplastic plasma cells interact with bone marrow microenvironment resulting in VEGF release leading to a new angiogenesis also supported by an inflammatory cells increase. The MCP-1 activates and promotes leukocyte-endothelium binding increasing the inflammatory process. The high correlation between MCP-1 and VEGF suggests a positive relationship between a new angiogenesis and a migration of inflammatory cells in the bone marrow stroma. On the basis of our results, MCP-1 and VEGF chemokines can be used to evaluate the inflammatory process in patient with systemic or localized AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

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IL-4 and IL-1 Serum Levels In Systemic and Localized Amyloidosis

Blood ◽

10.1182/blood.v116.21.5000.5000 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5000-5000

Author(s):

Alessandro Moscetti ◽

Francesca Saltarelli ◽

Guglielmo Bruno ◽

Bruno Monarca ◽

Gerardo Salerno ◽

...

Keyword(s):

Inflammatory Response ◽

Conflicts Of Interest ◽

Systemic Disease ◽

Inverse Correlation ◽

Serum Levels ◽

Systemic Amyloidosis ◽

Al Amyloidosis ◽

Th2 Response ◽

Localized Amyloidosis ◽

Localized Disease

Abstract Abstract 5000 AL amyloidosis is a plasmacellular discrasia characterized by the deposition of light chains fibrils that infiltrate tissues leading to multisystemic organ involvement. Amyloidosis can be systemic or localized disease. No immunological markers are avaibable to distinguish the systemic from localized disease. IL-4 and IL-1 cytokines were performed to evaluate if there is a different inflammatory pattern between the two clinical forms. IL-4 is the central regulator of T helper 2 (Th2) immune responses, with also a major impact on innate immune cells. IL-1 is produced by macrophages, monocytes, fibroblasts and dendritic cells which play an important role in the inflammatory response, activating the Th1-mediated IL2 release. IL-1 increases the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes to sites of infection. The study was devoted to evaluate serum levels of IL-4 and IL-1 in systemic or localized AL amyloidosis at presentation and to find out potential Th1 and Th2 disequilibrium. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. Serum IL-4 and IL-1 levels were detected. Mann-Whitney test and correlation test were used to analyze results. IL-4 level was significantly (p < 0.05) higher in patients with localized disease compared to the group with systemic amyloidosis. IL-1 was instead significantly (p < 0.01) increased in systemic disease. In this, an inverse correlation between IL-4 and IL-1a was found (r2= –0.707; p = 0.05). In systemic amyloidosis, the regulatory mechanism of Th1/Th2 response was polarized versus Th1, as demonstrated by low serum level of IL-4 and high level of IL-1. The negative correlation between serum IL-4 and IL-1 levels demonstrates a disregulation of the immune system in systemic disease as supported by the increased activity of Th1. The results seem to hypothesize that IL-4 could be able to antagonize the diffusion of disease, as demonstrated by the higher IL-4 serum levels in localized amyloidosis. So IL-4 and IL-1 can be considered sensible markers for the inflammatory response assessment both in systemic and localized amyloidosis. Disclosures: No relevant conflicts of interest to declare.

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NT-ProBNP and VEGF Serum Evaluation In AL Amyloidosis

Blood ◽

10.1182/blood.v116.21.5008.5008 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5008-5008

Author(s):

Francesca Saltarelli ◽

Alessandro Moscetti ◽

Maria Paola Bianchi ◽

Guglielmo Bruno ◽

Gerardo Salerno ◽

...

Keyword(s):

Cardiac Involvement ◽

Conflicts Of Interest ◽

Vascular Endothelial Cells ◽

Systemic Disease ◽

Serum Levels ◽

Systemic Amyloidosis ◽

The Other ◽

Al Amyloidosis ◽

Vascular Endothelial ◽

Heart Dysfunction

Abstract Abstract 5008 AL amyloidosis is a plasmacellular dyscrasia in which fibrillary deposits containing monoclonal immunoglobuline light chains infiltrate tissues causing their dysfunction and failure. Amyloidosis could be classified into rare localized or more frequent systemic forms such as AL amyloidosis. Cardiac dysfunction is a very frequent feature in AL amyloidosis patients. To evaluate heart involvement both in systemic and localized AL amyloidosis, serum levels of pro-BNP (peptide NT-proBNP; 76 amino acids) and VEGF were investigated. NT-proBNP has been described as an useful marker for heart dysfunction and its role as a prognostic factor for patients with systemic AL amyloidosis has been validated. VEGF is a signaling protein that stimulates new blood vessel formation and showed to be a mitogen for vascular endothelial cells. Serum NT-proBNP and VEGF levels were performed in systemic or localized AL amyloidosis patients to evaluate if there is any correlation between them. Blood samples were collected from 8 patients with systemic amyloidosis and from 4 patients with localized amyloidosis. To analyze the results of NT-proBnp and VEGF, Mann-Whitney test and Spearman correlation were performed. Serum NT-proBNP values were significantly increased in systemic disease (p=0.004). VEGF serum levels were also significantly higher in patients with systemic disease compared to the other group (p=0.027). No significant correlation between NT-proBNP and VEGF levels was found. We know that proBNP levels are significantly increased in patients with systemic amyloidosis and cardiac involvement. On the other hand, VEGF serum levels resulted to be increased in systemic disease. Nevertheless, on the basis of our results, we found absence of a significant correlation between NT-proBNP and VEGF increases. In our opinion, such finding could suggest that VEGF based neoangiogenesis is not significantly involved in AL amyloidosis heart dysfunction. Disclosures: No relevant conflicts of interest to declare.

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MR-Proanp and VEGF As Markers of Response to MEL-DEX Treatment in Systemic AL Amyloidosis

Blood ◽

10.1182/blood.v120.21.4970.4970 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4970-4970

Author(s):

Alessandro Moscetti ◽

Giusy Antolino ◽

Federica Resci ◽

Daniela De Benedittis ◽

Virginia Naso ◽

...

Keyword(s):

Stress Responses ◽

Plasma Cells ◽

Disease Risk ◽

Conflicts Of Interest ◽

Serum Levels ◽

Response To Treatment ◽

Al Amyloidosis ◽

Significant Independent Predictor ◽

Heart Involvement ◽

Cell Mitogen

Abstract Abstract 4970 Background. The natriuretic peptides are a family of different biomarkers including NT-proBNP and MR-proANP. As recommended by guidelines, they are important in heart failure diagnosis and monitoring. MR-proANP (1–98) is the mid-regional portion of the active atrial natriuretic peptide prohormone (99–126) and is considered a significant independent predictor of death, adding prognostic value to NT-proBNP. Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen with angiogenic and nonangiogenic role in several disorders including cardiovascular ones. Moreover, it regulates multiple cellular stress responses, including survival, proliferation, migration and differentiation. Systemic AL amyloidosis represents a peculiar disease with a clinical heart involvement that needs of a specific monitoring in order to avoid poor outcome. Aims and Methods. The study was devoted to evaluate treatment related changes in cardiovascular activity by MR-proANP and VEGF serum levels in systemic AL amyloidosis. Blood samples were collected from 8 patients with systemic AL amyloidosis (median age 72. 8 yrs) admitted to our Unit and analyzed for serum MR-proANP (mean±SD) and VEGF levels (Kits Brahms MR-proANP Kryptor and Randox Evidence Biochips Arrays). According to age and disease risk stratification all patients were treated with upfront oral Mel-Dex association (Melphalan 9 mg/sm, Dexamethasone 20mg day 1–4 q28). From each patient 2 samples of peripheral blood were performed (T0: at exordium of disease and T1: at conclusion of the first course of treatment). The sera were frozen to −80°C until their use. The results were analyzed by paired t test and Person correlation, p values ≤ 0. 05 were considered statistically significant. Results. VEGF serum levels were significantly (p=0. 01) reduced at the end of the first course of treatment (M±SD: T0: 282. 3 ± 86. 23 pg/mL vs. T1: 189. 7 ± 64. 24 pg/mL). Also MR-proANP serum levels were significantly decreased (M±SD: T0: 204. 4 ± 28. 82 pmol/L vs. T1: 160. 2 ± 21. 05 pmol/L, p=0. 008; see figure). The decreases of VEGF and MR-proANP were significantly (r =0. 79; p=0. 02) related. Conclusions. MR-proANP serum levels reduction could be hypothized as related to the decrease of inflammatory activity of disease, including heart involvement and a consequent reduced probability of fatal events. Our hypothesis seems to be confirmed by VEGF serum level reduction suggesting an inhibition of new angiogenesis with reduced interactions between neoplastic plasma cells and bone marrow microenvironment. The effective role of treatment in reducing the disease activity is demonstrated by the significant correlation between VEGF and MR-proANP level decreases. MR-proANP and VEGF could be used to evaluate and select systemic AL amyloidosis patients with an early good response to treatment. Disclosures: No relevant conflicts of interest to declare.

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Valuation of MIP-1α and MR-Proadm in Serum of Patients with Systemic AL Amyloidosis

Blood ◽

10.1182/blood.v120.21.4995.4995 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4995-4995

Author(s):

Giusy Antolino ◽

Alessandro Moscetti ◽

Federica Resci ◽

Daniela De Benedittis ◽

Virginia Naso ◽

...

Keyword(s):

Conflicts Of Interest ◽

Statistical Tests ◽

Rank Correlation ◽

Serum Levels ◽

Organ Damage ◽

Systemic Amyloidosis ◽

Control Group ◽

Al Amyloidosis ◽

Blood Draw ◽

Markers Of Inflammation

Abstract Abstract 4995 Background. AL systemic amyloidosis is the most common and lethal form of amyloidosis. Macrophage inflammatory protein-1 alpha (MIP-1α) is a member of the CC chemokine family which is primarily associated with cell adhesion and migration. Adrenomedullin, and more the mid-regional fragment of proadrenomedullin (MR-proADM), comprising amino acids 45–92, have immune modulating, metabolic and vascular actions. Aims and Methods. Aim of the study was to evaluate MIP-1α and MR-proADM serum levels in patients with systemic AL λ amyloidosis at presentation to find out potential differences useful to define a characteristic inflammatory pattern. Blood samples were collected from 7 patients with systemic AL amyloidosis (median age 68 yrs) and from 10 age-matched healthy control individuals referred to our Unit and analyzed for serum MIP-1 α and MR-proADM levels. For every patient 1 sample of peripheral blood have been obtained. The blood was separated into plasma at the time of blood draw and frozen to −80°C. Two-group comparisons were performed using the Mann-Whitney U test and paired t test. Correlation analyses were performed using Spearman rank correlation. All statistical tests were two tailed and p < 0. 05 was considered statistically significant. Results. Serum MIP-1α levels were significantly higher in AL amyloidosis patients (median 25. 04 pg/mL; IQR 12. 77) compared to the control group (median 2. 54 pg/mL; IQR 0. 34; p=0. 0007). Also serum MR-proADM levels were significantly increased in AL amyloidosis patients (median 1. 15 nmol/L, IQR 0. 6 vs median 0. 42 nmol/L, IQR 0. 18; p=0. 0008). In addition, a positive correlation between MIP-1α and MR-proADM has been observed in the group of patients with systemic amyloidosis (r2=0. 82, p=0. 034). Conclusions. The increase of MIP-1α and MR-proADM serum levels in patients with systemic AL amyloidosis at presentation is indicative of active basal inflammation which can contribute to organ damage, in particular heart and kidneys, due to microvascular impairment. On the basis of our results, MIP-1α and MR-proADM could be used as new serum markers of inflammation in AL amyloidosis patients, with possible role in monitoring of organ damage. Disclosures: No relevant conflicts of interest to declare.

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Osteopontin Predicts for Survival and Cystatin C-Based Estimated GFR Predicts for Renal Response to Therapy in Patients with Primary Systemic Amyloidosis

Blood ◽

10.1182/blood.v112.11.2731.2731 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2731-2731

Author(s):

Evangelos Terpos ◽

Efstathios Kastritis ◽

Evelina Charitaki ◽

Michalis Michail ◽

Georgios Boutsikas ◽

...

Keyword(s):

Cystatin C ◽

Univariate Analysis ◽

Serum Levels ◽

Response To Therapy ◽

Systemic Amyloidosis ◽

Cysteine Proteinase Inhibitor ◽

Age And Gender ◽

Renal Response ◽

Heart Involvement ◽

And Gender

Abstract Primary systemic amyloidosis (AL) is a multisystemic disorder resulting from an underlying plasma cell dyscrasia. Elevated serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is considered as one of the most powerful prognostic markers in AL. Angiogenesis is a crucial step for disease progression in several malignancies, including multiple myeloma (MM). Osteopontin (OPN) is a glycophosphoprotein cytokine, which has significant role in cell adhesion, prevention of apoptosis, invasion, migration and tumor cell growth. OPN also participates in neo-angiogenesis process in malignancies, as in MM. Renal involvement is common in AL, resulting in renal impairment in a significant proportion of patients. Cystatin-C (Cys-C) is a cysteine-proteinase inhibitor, which is considered as a reliable endogenous marker of GFR. Furthermore, our group has shown that Cys-C is an independent prognostic factor in MM. The aim of this study was to evaluate the levels of OPN, Cys-C and angiogenesis cytokines in AL, explore possible correlations with clinical characteristics and known prognostic factors, as NT-proBNP, and compare the results with those of MM. Serum levels of angiopoietin-1 and -2 (Ang-1, Ang-2), VEGF, angiogenin, basic fibroblast growth factor (bFGF) and OPN were evaluated using ELISA methodology (R&D, Minneapolis, MN, USA, for all, except of OPN: IBL GmbH D, Hamburg, Gemany). Serum Cys-C was determined by particle enhanced immunonephelometry (Dade Behring, Liederbach, Germany), while serum NT-proBNP was evaluated using an electrochemiluminescensce immunoassay (Roche Diagnostics GmbH, Mannheim, Germany). Serum samples were collected from 82 previously untreated AL patients (39M/43F), 35 age- and gender-matched healthy controls and 35 newly diagnosed, untreated, MM patients of similar age and gender. The median age of AL patients was 63 years (range: 39–86 years), and the median number of involved organs was 2 (range: 1–4). Heart was involved in 45 (56%) patients, kidney in 61 (76%) and liver in 11 (14%) patients. Serum levels of OPN (<0.01), VEGF (p<0.001), bFGF (<0.001), angiogenin (p<0.001) and Ang-2 (p<0.001) were significantly higher in AL patients than in controls; however Ang-1 levels did not differ between AL patients and controls (p=0.321), thus the ang1/ang2 ratio was lower in AL patients (p=0.036). Compared to MM patients, AL patients had significantly higher VEGF (p<0.001), angiogenin (p<0.001), and Ang-1 (p=0.001) levels but lower levels of Ang-2 (0.001) resulting in a significantly higher Ang-1/2 ratio (p<0.001). OPN levels did not differ between AL and myeloma patients (p=0.169). OPN correlated with NT-proBNP levels in AL (r=0.342, p=0.004). Ang-2 levels were significantly higher in AL patients with heart involvement (p=0.008) resulting in lower Ang-1/2 ratio (p=0.03). Cys-C levels were higher in AL patients compared to both controls and MM patients (p<0.0001). The eGFR estimated with the MDRD equation and 3 different equations that included Cys-C only; Cys-C and age; and Cys-C, creatinine and age (Stevens et al, Am J Kidney Dis2008;51:396–406) were 65, 44, 41 and 45 ml/min/1.73m2, respectively (p<0.001). All eGFR evaluations were associated with the probability of renal response to therapy. However, in multivariate analysis, only the equation that included Cys-C, creatinine and age predicted indepedently for renal response to therapy (HR 8.8, 95% CI 1.2– 67, p=0.033). The median survival of this cohort of patients has not been reached yet; the 24-month survival rate was 66%. In univariate analysis high NT-proBNP levels (p<0.001), heart involvement (p<0.01), ejection fraction <55% (p<0.01), high serum OPN (p=0.01), performance status ≥2 (p=0.011), ≥2 involved organs (p=0.02), no organ response to therapy (p=0.023), urine albumin (>3500 mg/24h; p=0.031), and no hematologic response to therapy (p=0.034) predicted for poor survival. However, NT-proBNP and OPN were both independently associated with survival in a multivariate model. This study suggests that angiogenesis cytokines are increased in AL, even compared to MM. More importantly, high OPN levels predicts for inferior survival, while eGFR based on Cys-C, creatinine and age predicts for renal response to therapy. NTproBNP remains a valuable predictive factor for survival in AL.

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Dysautonomias in amyloidosis

Nervenheilkunde ◽

10.1055/s-0038-1628501 ◽

2013 ◽

Vol 32 (04) ◽

pp. 192-196

Author(s):

B. P. C. Hazenberg

Keyword(s):

Cell Clone ◽

Early Stage ◽

Systemic Disease ◽

Interdisciplinary Approach ◽

Signs And Symptoms ◽

Systemic Amyloidosis ◽

Al Amyloidosis ◽

Life Threatening ◽

The Individual ◽

Common Manifestation

SummarySystemic amyloidosis is a life-threatening and frequently unrecognized cause of dysautonomia. Autonomic neuropathy is a common manifestation of AL amyloidosis (caused by deposition of an immunoglobulin free light chain produced by an underlying plasma cell clone) and of autosomal dominant hereditary ATTR amyloidosis (caused by a transthyretin mutation). The following review aims to alert clinicians to look out for signs and symptoms of amyloidosis to enable the bioptic diagnosis at an early stage. Suspicion of systemic amyloidosis is usually raised by the systemic, multi-organ character of the disease. An interdisciplinary approach is needed in the individual patient in order to establish the diagnosis and to obtain a clear overview of the actual multitude of organ problems. This overview is necessary for risk management and for making a well-considered treatment choice. Collaboration of all medical specialists involved is necessary to deliver optimal treatment and care to the patient with this systemic disease.

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Biomarkers of Hemolysis and Inflammation in Sickle Cell Disease Children: Association with Nasopharynx and Oropharynx Bacteria colonization

Blood ◽

10.1182/blood.v118.21.2140.2140 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2140-2140

Author(s):

Larissa Rocha ◽

Magda Seixas ◽

Bruno A. V. Cerqueira ◽

Valma Lopes ◽

Mitermayer Reis ◽

...

Keyword(s):

Conflicts Of Interest ◽

Systemic Disease ◽

Female Gender ◽

Serum Levels ◽

Cross Sectional Study ◽

Initiation Factor ◽

Nasopharyngeal Colonization ◽

High Count ◽

Cross Sectional ◽

Alpha 1 Antitrypsin

Abstract Abstract 2140 Introduction: Nasopharynx and oropharynx bacterium colonization can be considered as initiation factor for local or systemic disease. The Streptococcus pneumoniae is a pathogen with epidemiological worldwide importance and it has been frequently associated with infection among SCD patients. The Staphylococcus aureus may also colonize the nasopharynx and has been associated with cause of infections in skin and soft tissue, pneumonia, sepsis, osteoarticulation. This study aimed to establish a profile of inflammation and hemolysis biomarkers of SCD individuals in association with the oropharyngeal and nasopharyngeal bacteria colonization. Patients and Methods: Biomarkers related to hemolysis and inflammation, including lipids and liver function, were determined by biochemical colorimetric reaction and also myeloperoxidase (MPO) gene polymorphisms were investigated with PCR and RFLP techniques. Medical history was obtained by patients' record. Thus, it was developed a cross-sectional study composed by 154 SCD children in a steady-state from the Bahia state, in Brazil, 68.2% (105/154) with HbSS genotype, and 31.8% (49/154) HbSC, in attendance of the outpatients clinic of the Foundation of Hematology and Hemotherapy of Bahia (HEMOBA). The study was approved by the Human research board from FIOCRUZ-BA and every official responsible signed an informed consent. Results: Nasopharynx and oropharynx colonization by S. pneumoniae was found in 14 (9.6%) SCD patients and by S. aureus in 81 (56.6%) patients, and both SCD genotypes had similar frequencies of these studied bacteria. It was not observed an increase in pneumococcal penicillin resistance. SCD patients with nasopharynx colonization by S. pneumoniae and S. aureus exhibited higher ferritin serum levels than patients with a normal microbiote respectively (p=<0.0001; p=0.0144, Mann-Whitney test). However, SCD patients with S. pneumoniae colonization had the highest ferritin serum levels. SCD patients with oropharynx colonization by S. pneumoniae exhibited the highest ferritin (p<0.0001), alanine transaminase (p=0.002) and aspartate aminotransferase (p<0.0001) serum levels when compared with SCD patients colonized by S. aureus and with normal microbiote. Evaluation of multivariate analysis models by logistic regression showed that the occurrence of infection was associated with a high number of total leukocytes (OR:3.41; CI:1.35–8.60; p=0.0092) in a model involving high levels of alpha 1-antitrypsin, antistreptolysin O, the mutant allele of myeloperoxidase gene, and nasopharynx colonization; infection was also associated in a model involving oropharynx colonization (OR:3.87; CI:1.43–10.50;p=0.008) and high leukocytes number (OR:10.13; CI:10.13–52.43; p=0.006), and high count of reticulocyte, platelets, and neutrophils. Pneumonia occurrence was associated with the HbSS genotype (OR:4.55; CI:1.56–13.31;p=0.006) in models involving oropharyngeal or nasopharyngeal colonization, and high count of reticulocyte, platelets, and neutrophils, and age less than 5 years old. Interestingly, when vaso-occlusive was analyzed, the involvement of oropharyngeal or nasopharyngeal colonization was not pivotal for this event, that was associated to high neutrophils counts (OR:11.75; CI:2.33–59.26; p=0.003) in the presence of high count of reticulocyte, platelets, leukocytes, female gender and age less than 5 years old. Conclusion: Ours result of SCD patients nasopharynx and oropharynx colonization with high ferritin serum levels may be associated with an increase of oxygen and nitrogen reactive species by bacteria presence, suggesting a pivotal role of the bacteria colonization in the modulation of hemolytic events, inflammation state, and infectious occurrence and a possible influence in the disease severity. Disclosures: No relevant conflicts of interest to declare.

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Presentation and Outcomes of Localized Amyloidosis: The Mayo Clinic Experience

Blood ◽

10.1182/blood.v126.23.4197.4197 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4197-4197 ◽

Cited By ~ 3

Author(s):

Taxiarchis Kourelis ◽

Francis Buadi ◽

Morie A Gertz ◽

Shaji Kumar ◽

Martha Q. Lacy ◽

...

Keyword(s):

Light Chain ◽

Mayo Clinic ◽

Systemic Disease ◽

Systemic Amyloidosis ◽

Upper Respiratory Tract ◽

Light Chain Amyloidosis ◽

Localized Amyloidosis ◽

Clinic Experience ◽

Clinical Records

Abstract Introduction: Localized immunoglobulin light chain amyloidosis (LAL) is a rare disease. Systematic data regarding its presentation, management and patient outcomes are limited to small case series. Our objective was to systematically describe the Mayo clinic experience of patients with LAL. Methods: We retrospectively reviewed clinical records of 403 patients with biopsy proven localized amyloidosis seen at the Mayo Clinic between 1969-2014. Median follow-up for survival and progression were 72 months and 39 months, respectively Results: OF 5551 patients with light chain amyloidosis seen at the Mayo clinic during the study period, 403 (7%) had LAL. Median age at diagnosis was 60 years (range, 13-93) and 51% of them were male. Sites involved included: urothelial (bladder, ureter, renal pelvis), 75 (19%), larynx, 51 (13%), lung parenchyma, 42 (11%), skin, 44 (11%), synovial tissue 36 (9%), tracheobronchial, 31 (8%), gastrointestinal tract, 30 (8%), seminal vesicles, 22 (6%), eyes, 23 (6%), pharynx 22 (6%) and other 24 (6%). Typing was performed in 178 (45%) cases. A monoclonal protein was detected in 23 of 351 (7%) evaluated cases, 5 of which had different light restriction from that of LAL. Thirty one (8%) patients had a co-existent autoimmune disease. No patients progressed to systemic AL. Of 403, 109 (27%) were observed or received supportive care only and 241 (60%) underwent local removal of the amyloid deposits. Sixty-four (16%) patients required repeated interventions (median 1, range 1-4, upper decile requiring 4 interventions) for progressive disease. The most common sites requiring repeated interventions were: urothelial (33%), laryngeal (19%) and tracheobronchial (8%). Ten year overall survival (OS) and progression free survival were 79% and 61%, respectively and there was no difference according to site of involvement. Of the 70 patients that died during the follow-up period, cause of death was known for 29 and death was attributed to LAL in only 2 cases. Conclusions: In the largest series of patients with LAL reported so far we demonstrated that LAL has an excellent prognosis but can sometimes be associated with significant morbidity. Although our study was limited by incomplete typing in 55% of cases, it appears that true LAL does not "progress" to systemic amyloidosis. However, systemic amyloidosis can frequently involve organs typical involved only in LAL;, therefore a complete work-up for systemic disease should be performed in all patients with LAL. Treatment usually involves local excision for symptom palliation. In 16% of cases, repeated interventions for relapse/progression were required and as a result, follow-up is recommended, especially for cases involving the urothelial and upper respiratory tract. Disclosures Kumar: Skyline, Noxxon: Honoraria; Celgene, Millennium, Onyx, Novartis, Janssen, Sanofi: Research Funding; Celgene, Millennium, Onyx, Janssen, Noxxon, Sanofi, BMS, Skyline: Consultancy.

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The Role of Light Kappa and Lambda Chains in Heart Function Assessment in Patients with AL Amyloidosis

Journal of Clinical Medicine ◽

10.3390/jcm10061274 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1274

Author(s):

Emilia Czyżewska ◽

Agnieszka Wiśniewska ◽

Anna Waszczuk-Gajda ◽

Olga Ciepiela

Keyword(s):

Troponin I ◽

Heart Function ◽

Myocardial Dysfunction ◽

Interventricular Septum ◽

Myocardial Damage ◽

Amyloid Deposit ◽

Al Amyloidosis ◽

Heart Involvement ◽

Immunoglobulin Light Chain Amyloidosis

There are reports indicating that myocardial dysfunction in systemic immunoglobulin light chain amyloidosis (AL amyloidosis) stems not only from the amyloid deposit in the organ but also the cardiotoxicity of the amyloid precursor free light chains (FLCs) circulating in the blood. The aim of the study is to analyze the role of sFLC κ and λ in the assessment of heart involvement and the degree of myocardial damage in AL amyloidosis. The study involved 71 patients diagnosed with primary AL amyloidosis. The relationship between sFLC concentrations and cardiac biochemical and echocardiographic parameters was assessed. The median concentrations of N-terminal pro b-type natriuretic peptide(NT-proBNP) and troponin I (TnI) were significantly higher in patients with amyloids formed from monoclonal λ chains compared to patients with monoclonal κ proliferation. In patients with heart involvement by amyloids formed from monoclonal FLC, the study demonstrated a statistically significant positive correlation between the concentration of monoclonal antibody λ chain and TnI (R = 0.688; p < 0.05), NT-proBNP (R = 0.449; p < 0.05), and the value of diastolic dimension of the interventricular septum (IVS; R = 0.496, p < 0.05). The above data indicate that the presence of monoclonal λ chains in patients with AL amyloidosis may be associated with more severe damage to cardiomyocytes and dysfunction of the myocardium.

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