Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.197
Filtrar
1.
Virchows Arch ; 477(4): 565-572, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32300880

RESUMO

IgA nephropathy (IgAN) is common chronic glomerulonephritis with variable prognosis, ranging from minor urinary abnormalities to end-stage renal disease. The revised Oxford classification of IgAN explains that cellular/fibrocellular crescents are associated with poor renal prognosis, proposing an extension to the MEST-C score. C3 immunofluorescent staining follows a distribution similar to IgA staining. Therefore, complement activation was reported to play a pivotal role in IgAN pathogenesis. This study included 132 IgAN patients diagnosed by renal biopsies. The clinical parameters at the time of the biopsies were obtained from patient data records. We classified the patients into C ≥ 1 and C0 groups, and compared clinical, light microscopic, and immunofluorescent features. In the C ≥ 1 group, 2 (1.5%) and 31 (23.5%) patients were assigned to C2 and C1, respectively. The remaining 99 patients (75%) were classified as C0. The C ≥ 1 group had lower average age and rate of hypertension, and higher score of urinary occult blood and E score. The C ≥ 1 group had significantly higher average immunofluorescence scores for IgA, C5b-9, mannose-associated serine protease (MASP) 1/3, MASP2, properdin, factor B, and kappa. The steroid use rate was significantly higher in the C ≥ 1 group. During the follow-up period of 2.90 years on average, the rate of renal dysfunction was not significantly different between groups. Crescent formation in IgAN was associated with activation of the lectin and alternative pathways. The C ≥ 1 group had significantly increased use of steroids, which probably caused comparable renal function during the follow-up period.


Assuntos
Ativação do Complemento , Proteínas do Sistema Complemento/análise , Glomerulonefrite por IGA/imunologia , Imunoglobulina A/análise , Glomérulos Renais/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Complemento C3/análise , Fator B do Complemento/análise , Complexo de Ataque à Membrana do Sistema Complemento/análise , Feminino , Imunofluorescência , Glomerulonefrite por IGA/patologia , Humanos , Cadeias Leves de Imunoglobulina/análise , Japão , Glomérulos Renais/patologia , Masculino , Serina Proteases Associadas a Proteína de Ligação a Manose/análise , Microscopia de Fluorescência , Pessoa de Meia-Idade , Properdina/análise , Estudos Retrospectivos , Adulto Jovem
2.
Clin Nephrol ; 93(4): 203-208, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31907143

RESUMO

Plasma cell dyscrasias, including multiple myeloma (MM), are associated with diverse forms of pathology in the kidney. Some pathologic lesions, including light chain (myeloma) cast nephropathy (LCCN), are relatively common, while others, such as light chain proximal tubulopathy (LCPT), are less so. Both LCCN and LCPT are associated with clinical manifestations of acute kidney injury. Rare instances of coincidental LCPT and LCCN have been reported, but none to our knowledge of coincidental crystalline forms of these diseases, with similar forms appearing in the urine. While LCPT is usually associated with intracytoplasmic deposition of crystallized light chains, the intraluminal light chain casts in LCCN are typically amorphous and do not form crystals. We report here the co-occurrence of these two monoclonal crystalline forms of acute kidney injury in a 66-year-old woman with known history of κ-restricted multiple myeloma. Additionally, forms suggestive of a crystalline morphology were observed in the urine sediment. Clinicians who observe similar crystalline structures on renal biopsy or in urine sediment should have a high index of suspicion for underlying multiple myeloma as a unifying diagnosis.


Assuntos
Lesão Renal Aguda/complicações , Cadeias Leves de Imunoglobulina/análise , Túbulos Renais Proximais/patologia , Mieloma Múltiplo/patologia , Idoso , Cristalização , Feminino , Humanos , Nefropatias/patologia , Mieloma Múltiplo/urina , Urina/citologia
3.
J Immunol Methods ; 476: 112683, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682797

RESUMO

The expression levels of immunoglobulin elements and their receptors are important markers for health and disease. Within the immunoglobulin locus, the constant regions and the variable region families are associated with certain pathologies, yet a holistic view of the interaction between the expressions of the multiple genes remain to be fully characterized. There is thus an important need to quantify antibody elements, their receptors and the receptor subunits in blood (PBMC cDNA) for both screening and detailed studies of such associations. Leveraging on qPCR, we designed primers for all Vκ1-6, VH1-7, Vλ1-11, nine CH isotypes, Cκ, Cκ, Cλ1 &3, FcεRI α,ß, and γ subunits, all three FcγR and their subunits, and FcαR. Validating this on a volunteer PBMC cDNA, we report a qPCR primer set repertoire that can quantify the relative expression of all the above genes to the GAPDH housekeeping gene, with implications and uses in both clinical monitoring and research.


Assuntos
Primers do DNA , Sistema Imunitário/fisiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptores Fc/genética , DNA Complementar , Expressão Gênica , Humanos , Cadeias Pesadas de Imunoglobulinas/análise , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Leves de Imunoglobulina/análise , Cadeias Leves de Imunoglobulina/genética , Região Variável de Imunoglobulina/análise , Região Variável de Imunoglobulina/genética , Leucócitos Mononucleares , RNA Mensageiro/análise , Receptores Fc/análise
4.
Saudi J Kidney Dis Transpl ; 30(5): 1161-1165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31696857

RESUMO

Light-chain deposition disease (LCDD) reoccurs almost invariably after renal transplantation, leading to early graft loss. We report a case of LCDD with monoclonal gammopathy of renal significance diagnosed in the post-transplant period in a 28-year-old male and we discuss the diagnostic and therapeutic challenges in the clinical course.


Assuntos
Glomerulonefrite/imunologia , Cadeias Leves de Imunoglobulina/análise , Transplante de Rim/efeitos adversos , Rim/imunologia , Paraproteinemias/imunologia , Adulto , Biomarcadores/análise , Glomerulonefrite/diagnóstico , Glomerulonefrite/terapia , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Paraproteinemias/diagnóstico , Paraproteinemias/terapia , Diálise Renal , Resultado do Tratamento
6.
BMC Res Notes ; 12(1): 571, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511043

RESUMO

OBJECTIVE: Gastrointestinal tract lymphomas are currently detected more frequently due to advances in endoscopic technology. The aim of this study was to assess the feasibility of flow cytometric analysis of restricted light chain in endoscopic biopsy specimens for the diagnosis of gastrointestinal tract B-cell lymphoma. We prepared viable cell suspensions from unfixed specimens obtained from 10 consecutive patients who had a previous histological diagnosis of gastrointestinal tract B-cell lymphoma. We performed immunophenotypic studies with multi-color flow cytometry and assessed clonality through examination of immunoglobulin light chain expression exclusively in a population identified by anti-CD45 or CD20 antibodies. RESULTS: We could perform light chain expression analysis with 2 endoscopic biopsy specimens from all 10 patients with gastrointestinal tract B-cell lymphoma. We conclude that flow cytometric analysis of endoscopic biopsy specimens is feasible and thus likely useful for the diagnosis of gastrointestinal tract B-cell lymphoma in clinical settings. Trial registration UMIN Clinical Trials Registry, UMIN000027730. Registered 12 June 2017.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Citometria de Fluxo/métodos , Neoplasias Gastrointestinais/imunologia , Cadeias Leves de Imunoglobulina/análise , Linfoma de Células B/imunologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/patologia , Estudos de Viabilidade , Feminino , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Humanos , Cadeias Leves de Imunoglobulina/imunologia , Imunofenotipagem , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto
7.
Ann Biol Clin (Paris) ; 77(4): 397-406, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31418701

RESUMO

Immunoglobulin light chains are called free when they are not linked with heavy chains to form a whole immunoglobulin. Quantification of free light chains is a part of the French national authority for health guidelines for diagnostic and follow-up of light chain, oligo or non-secretory myeloma and AL amyloidosis. Most recently, the World health organisation had included free light chains quantification in prognostic criteria for monoclonal gammopathy of undetermined significance. However the literature bring to light some other potential indications of this analysis in the exploration of monoclonal gammopathy, also in lymphoid malignancies and some autoimmune diseases such as diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and Sjögren syndrome.


Assuntos
Doenças Autoimunes/diagnóstico , Neoplasias Hematológicas/diagnóstico , Cadeias Leves de Imunoglobulina/sangue , Paraproteinemias/diagnóstico , Testes Sorológicos , Doenças Autoimunes/sangue , Doenças Autoimunes/imunologia , Diagnóstico Diferencial , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/imunologia , Humanos , Cadeias Leves de Imunoglobulina/análise , Amiloidose de Cadeia Leve de Imunoglobulina/sangue , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Paraproteinemias/sangue , Paraproteinemias/imunologia , Valor Preditivo dos Testes , Prognóstico , Testes Sorológicos/métodos , Testes Sorológicos/normas
8.
Br J Haematol ; 187(4): 459-469, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31348519

RESUMO

Renal involvement is found in about 70% of patients with systemic immunoglobulin light-chain (AL) amyloidosis. However, there is no risk stratification system specialized for renal AL concerning patients' survival. Galectin-3 (Gal-3) has been reported to portend poor prognosis in other renal diseases. We measured Gal-3 and several traditional risk biomarkers of AL in baseline samples from 253 consecutive patients diagnosed with renal AL. At baseline, Gal-3 [Hazard ratio (HR): 1·46; P = 0·033], high-sensitivity cardiac troponin T (hs-cTnT) (HR: 2·65; P < 0·001) and difference between involved and uninvolved free light chains (dFLC) (HR: 1·81; P = 0·001) were independent predictors of all-cause mortality. The cut-off points for Gal-3, hs-cTnT, and dFLC were 20·24 ng/ml, 0·026 ng/ml, and 75·89 mg/l, respectively. Patients were stratified into four stages by assigning a score of 1 for each of the three biomarkers above the cut-off point. The proportions of patients with disease stages 1, 2, 3 and 4 were 17·0%, 37·2%, 29·2% and 16·6%, and the median overall survival times from diagnosis were 100, 60, 29 and 15 months, respectively (P < 0·01). Higher level of Gal-3 is associated with increased risk for mortality, and the risk stratification based on Gal-3 is a reliable model for predicting mortality in AL amyloidosis with renal involvement.


Assuntos
Galectina 3/análise , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Nefropatias/etiologia , Biomarcadores/análise , Humanos , Cadeias Leves de Imunoglobulina/análise , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Valor Preditivo dos Testes , Medição de Risco , Análise de Sobrevida , Troponina T/análise
9.
Clin Chem Lab Med ; 57(12): 2008-2018, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31199760

RESUMO

Background The aim of this study was to evaluate the diagnostic performance of cerebrospinal fluid (CSF) free light chains (FLCs) in the diagnosis of Lyme neuroborreliosis (LNB). Methods Serum and CSF levels of κ- and λ-FLC, albumin and total concentration of immunoglobulin M (IgM) were determined together with CSF chemokine CXCL13 in 23 patients with definite LNB, 35 inflammatory neurological disease control (INDC) and 18 non-inflammatory control (NIC) patients. Indices and intrathecal fractions (IFs) of FLC and IgM were calculated. Results Significant differences in FLC indices and IFs were found between the LNB group and both control groups, p ≤ 0.007. Sensitivity of intrathecal κ- and λ-FLC synthesis reached 78%-87% in LNB patients with a specificity of 94%-100% in NIC patients, whereas specificity in INDC patients was 69%. The corresponding frequencies of positive results for IF and index of IgM and CSF CXCL13 in these three diagnostic groups were 74%-96% in LNB patients, 0% in NIC patients and 3%-6% in INDC patients at the chosen cut-off levels. Conclusions The findings of this study show a moderate to high sensitivity of CSF κ- and λ-FLC in LNB patients with a high specificity in NIC patients. However, overlap in CSF κ- and λ-FLC levels between LNB and INDC patients calls for caution in the interpretation and limits the diagnostic usefulness in the LNB diagnosis. CSF CXCL13 appears to be the most valuable additional biomarker of LNB aside from routine parameters such as CSF pleocytosis and anti-Borrelia antibody index.


Assuntos
Cadeias Leves de Imunoglobulina/análise , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/diagnóstico , Adulto , Idoso , Biomarcadores/líquido cefalorraquidiano , Líquido Cefalorraquidiano/química , Quimiocina CXCL13/análise , Feminino , Humanos , Cadeias Leves de Imunoglobulina/líquido cefalorraquidiano , Imunoglobulina M/análise , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sensibilidade e Especificidade , Soro/química
10.
Clin Chem Lab Med ; 57(10): 1574-1586, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31112501

RESUMO

Background Free light chains (FLC) have been proposed as diagnostic biomarkers in the cerebrospinal fluid (CSF) of patients with inflammatory central nervous system (CNS) diseases. However, which method to use for determining an intrathecal FLC synthesis has not yet been clarified. The objective of this study was to compare the diagnostic performance of CSF FLC concentration, FLC quotient (QFLC), FLC index and FLC intrathecal fraction (FLCIF). Methods κ- and λ-FLC were measured by nephelometry under blinded conditions in CSF and serum sample pairs of patients with clinically isolated syndrome (CIS; n = 60), multiple sclerosis (MS; n = 60) and other neurological diseases (n = 60) from four different MS centers. QFLC was calculated as the ratio of CSF/serum FLC concentration, the FLC index as QFLC/albumin quotient and the percentage FLCIF by comparing QFLC to a previously empirically determined, albumin quotient-dependent reference limit. Results CSF FLC concentration, QFLC, FLC index and FLCIF of both the κ- and λ-isotype were significantly higher in patients with CIS and MS than in the control group, as well as in oligoclonal bands (OCB) positive than in OCB negative patients. Each parameter was able to identify MS/CIS patients and OCB positivity, however, diagnostic performance determined by receiver operating characteristic (ROC) analyses differed and revealed superiority of FLC index and FLCIF. Conclusions These findings support the diagnostic value of FLC measures that correct for serum FLC levels and albumin quotient, i.e. blood-CSF barrier function.


Assuntos
Cadeias Leves de Imunoglobulina/análise , Cadeias Leves de Imunoglobulina/líquido cefalorraquidiano , Imunoglobulinas/análise , Adulto , Áustria , Estudos Transversais , Doenças Desmielinizantes/imunologia , Testes Diagnósticos de Rotina/métodos , Feminino , Alemanha , Humanos , Isotipos de Imunoglobulinas/análise , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/líquido cefalorraquidiano , Cadeias Leves de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Imunoglobulinas/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Doenças do Sistema Nervoso/imunologia , Curva ROC
11.
Clin Chem Lab Med ; 57(9): 1397-1405, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-30973821

RESUMO

Background Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder with a high risk of progression to symptomatic multiple myeloma (MM). The serum free light chain (sFLC) ratio is a powerful prognostic factor for SMM: an sFLC ratio ≥8 has been reported to be associated with a high risk of progression to MM, and an sFLC ratio ≥100 has been described as a criterion for ultra-high-risk SMM, and has been integrated into the definition criteria for MM since 2014. However, all recommendations were based on sFLC measured using the first commercialized assay, Freelite™, while other assays are now available. We aimed to evaluate the safety and accuracy of N-Latex sFLC to identify high-risk and ultra-high-risk SMM. Methods The sFLC ratio was measured at diagnosis with both Freelite and N-Latex assays in a cohort of 176 SMM patients on a BN Prospec nephelometer. Demographic, clinical, therapeutic and laboratory data were collected at the time of diagnosis and at follow-up. Results Sixty-two patients (35.2%) progressed to MM within 2 years. Compared to Freelite™ sFLC, N Latex sFLC ratios ≥8 and ≥100 provided similar performances for the identification of high-risk and ultra-high risk SMM patients. Conclusions Our results evidenced that the N-Latex assay could be used for SMM monitoring, like Freelite. However, an N-Latex sFLC ratio ≥70 appears to provide similar performances to a Freelite sFLC ratio ≥100, with a slightly better positive predictive value. Both assays provided accurate identification of high-risk and ultra-high risk SMM patients. These results should be confirmed in an independent study.


Assuntos
Cadeias Leves de Imunoglobulina/análise , Mieloma Múltiplo Latente/diagnóstico , Idoso , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Cadeias Leves de Imunoglobulina/sangue , Cadeias kappa de Imunoglobulina/sangue , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Paraproteinemias/diagnóstico , Prognóstico , Fatores de Risco
12.
Rev Med Interne ; 40(5): 297-305, 2019 May.
Artigo em Francês | MEDLINE | ID: mdl-30862366

RESUMO

Serum free light chains (sFLC) assay is an important marker in plasma cell dyscrasia. It is thus recommended for the diagnosis of monoclonal gammopathy, together with serum protein electrophoresis and immunofixation. sFLC assay has also a prognostic value and is a criterion for treatment response and relapse of some monoclonal gammopathies. Three assays are currently available in France, the gold standard being the Freelite® assay, the two others requiring further validation. These three assays are not interchangeable during patient's follow-up. The Freelite® assay is integrated in the myeloma diagnostic criteria from the International Myeloma Working Group 2014, and has a higher sensitivity than Bence Jones protein test for diagnosis, treatment response and follow-up of light chain myeloma. The Freelite® assay is the main marker of therapeutic response in light chain amyloidosis and allows to stratify the risk for progression in monoclonal gammopathy of undetermined significance. Some studies have also shown its value in diagnosis of multiple sclerosis and in screening for monoclonal gammopathy in the cases of acute renal failure. The Freelite® assay is then currently essential in myeloma or amyloidosis, and could be soon extended to the management of autoimmune diseases.


Assuntos
Cadeias Leves de Imunoglobulina/análise , Paraproteinemias/diagnóstico , Testes Sorológicos , Humanos , Imunoensaio/métodos , Cadeias Leves de Imunoglobulina/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Paraproteinemias/sangue , Paraproteinemias/etiologia , Prognóstico , Testes Sorológicos/métodos , Testes Sorológicos/normas
13.
Gynecol Endocrinol ; 35(8): 710-713, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30835572

RESUMO

Polycystic ovary syndrome (PCOS), as systemic disease, is accompanied by different indexes of inflammation. Free light chains of immunoglobulins (FLCs), produced by plasmacells, are released in slight excess for the immune requests, with still poorly defined physiological role but surely they represent a marker of inflammation. In order to evaluate their levels and correlate them with hyperandrogenism, we have studied a group of PCOS patients, age range 18-37 yrs, mean ± SEM body mass index (BMI) 24.1 ± 0.9 kg/m2), compared with age- and BMI-matched controls, with assay of k and λ FLCs, by turbidimetric method, and their ratio in blood plasma. PCOs exhibited higher levels vs. controls: (mean ± SEM λ: 10.0 ± 0.85 mg/L vs. 8.41 ± 0.45 mg/L; k: 12.45 ± 0.72 mg/L vs. 6.41 ± 0.34 mg/L; k/λ: 1.31 ± 0.07 vs. 0.78 ± 0.04). A significant direct correlation was observed between λ-FLCs and testosterone levels, no correlation was indeed found with HOMA-IR index. These data confirm high levels of FLCs in PCOS, suggesting systemic inflammatory state and a possible role in the pathophysiology of such complex syndrome.


Assuntos
Cadeias Leves de Imunoglobulina/sangue , Síndrome do Ovário Policístico/sangue , Adolescente , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/complicações , Hiperandrogenismo/imunologia , Cadeias Leves de Imunoglobulina/análise , Inflamação/sangue , Inflamação/complicações , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/imunologia , Testosterona/sangue , Adulto Jovem
14.
Internist (Berl) ; 60(1): 10-22, 2019 01.
Artigo em Alemão | MEDLINE | ID: mdl-30635666

RESUMO

BACKGROUND: Kidney involvement is a common complication in patients with plasma cell diseases. OBJECTIVE: This article outlines the spectrum of renal involvement in plasma cell dyscrasia and describes diagnostic and therapeutic measures to guide clinical management. MATERIAL AND METHODS: Evaluation and discussion of the current literature as well as existing guidelines and recommendations of professional societies. RESULTS: The clinical manifestations of renal involvement in plasma cell disorders are heterogeneous and range from acute cast nephropathy in multiple myeloma to rare forms of glomerulonephritis. The term monoclonal gammopathy of renal significance (MGRS) was introduced to describe kidney involvement caused by monoclonal gammopathy but without evidence for underlying malignancy. Light chain cast nephropathy is the most common renal manifestation in multiple myeloma, whereas monoclonal immunoglobulin deposition disease (MIDD) and renal light chain (AL) amyloidosis can be found in multiple myeloma and MGRS. Decisive is the extended hematological diagnostics in order to exclude the presence of a hematological neoplasm. The treatment of renal involvement in monoclonal gammopathies involves the reduction of the plasma cell clone with cytoreductive treatment. The reduction of the monoclonal protein in serum is prognostically relevant for the renal response to treatment. In the case of histological evidence of a light chain cast nephropathy, high cut-off dialysis is recommended to reduce the free light chains in serum. CONCLUSION: The spectrum of renal manifestations in plasma cell dyscrasia has been expanded, particularly since the introduction of the term MGRS. Diagnostic and therapeutic management remain an interdisciplinary challenge.


Assuntos
Nefropatias/diagnóstico , Nefropatias/terapia , Rim/patologia , Mieloma Múltiplo/patologia , Paraproteinemias/patologia , Plasmócitos/patologia , Glomerulonefrite , Humanos , Cadeias Leves de Imunoglobulina/análise , Nefropatias/etiologia , Nefropatias/patologia , Mieloma Múltiplo/complicações , Paraproteinemias/complicações , Diálise Renal , Síndrome do Nó Sinusal/congênito
15.
Biol Chem ; 400(3): 383-393, 2019 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-30465712

RESUMO

Antibodies can be successfully engineered and isolated by yeast or phage display of combinatorial libraries. Still, generation of libraries comprising heavy chain as well as light chain diversities is a cumbersome process involving multiple steps. Within this study, we set out to compare the output of yeast display screening of antibody Fab libraries from immunized rodents that were generated by Golden Gate Cloning (GGC) with the conventional three-step method of individual heavy- and light-chain sub-library construction followed by chain combination via yeast mating (YM). We demonstrate that the GGC-based one-step process delivers libraries and antibodies from heavy- and light-chain diversities with similar quality to the traditional method while being significantly less complex and faster. Additionally, we show that this method can also be used to successfully screen and isolate chimeric chicken/human antibodies following avian immunization.


Assuntos
Cadeias Pesadas de Imunoglobulinas/análise , Cadeias Leves de Imunoglobulina/análise , Saccharomyces cerevisiae/química , Animais , Galinhas , Clonagem Molecular , Humanos , Cadeias Pesadas de Imunoglobulinas/imunologia , Cadeias Leves de Imunoglobulina/imunologia , Biblioteca de Peptídeos , Engenharia de Proteínas , Saccharomyces cerevisiae/imunologia , Propriedades de Superfície
16.
BMJ Case Rep ; 11(1)2018 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-30580293

RESUMO

Light chain cast nephropathy is the most frequent form of renal disease in plasma cell neoplasm showing precipitation of monoclonal immunoglobulin light chains in the lumen of the distal tubules. This has a typical morphological feature characterised by the presence of a fractured cast. In this article, we report an unusual case of light chain cast nephropathy exhibiting amyloidogenic potential with lamellated, spiculated appearance. These casts were positive for periodic acid-Schiff and Jones' silver stain, fuchsinophilic in Masson trichrome stain and showed apple-green birefringence under polarised light in Congo red stain. Complete haematological evaluation confirmed the presence of underlying plasma cell myeloma. The connotation of intratubular amyloid cast lies in the fact that this may represent an early phenomenon during the development of light chain cast nephropathy-associated systemic amyloidosis and may precede the formation of light chain amyloid in renal or extrarenal location.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Nefropatias/patologia , Mieloma Múltiplo/patologia , Amiloide/análise , Biópsia , Humanos , Cadeias Leves de Imunoglobulina/análise , Rim/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Intern Med ; 57(24): 3597-3602, 2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30101939

RESUMO

Light Chain Proximal Tubulopathy (LCPT) is a rare form of paraprotein-related kidney disease in which monoclonal free light chains damage the proximal renal tubular epithelial cells. We herein report the case of a 78-year-old woman who presented with anemia and kidney dysfunction. Serum and urine protein electrophoresis analyses revealed a monoclonal IgD and λ free light chains. Proximal tubular injury and the accumulation of λ light chains were found by kidney biopsy. Electron microscopy revealed no organized structure suggestive of crystals. LCPT was caused by IgD lambda myeloma and bortezomib and dexamethasone therapy led to very good partial response (VGPR) without a worsening of the kidney function.


Assuntos
Imunoglobulina D/análise , Cadeias Leves de Imunoglobulina/análise , Nefropatias/complicações , Nefropatias/imunologia , Túbulos Renais Proximais/imunologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/imunologia , Idoso , Anemia/etiologia , Antineoplásicos/uso terapêutico , Biópsia , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Feminino , Humanos , Nefropatias/patologia , Nefropatias/fisiopatologia , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/fisiopatologia , Mieloma Múltiplo/fisiopatologia
19.
Clin Chem Lab Med ; 57(2): 221-229, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30032127

RESUMO

Background The automated immunochemical serum free light chains (FLC) assays, Freelite (a polyclonal antiserum) and N Latex FLC (a mixture of monoclonal antibodies), are not interchangeable, as they may provide different results on a same sample. This study was aimed to establish if the calibrators contain FLC oligomers, and if different reactivity against monomers and dimers contributes to the discrepancy. Methods Gel filtration chromatography fractions of the calibrators were subjected to a Western blot (WB) and analyzed by each reagent. The procedure was repeated after pretreating the N Latex FLC calibrator with the reducing agent dithiothreitol (DTT). Results Both calibrators contain FLC dimers and monomers. Both reagents detect (with different sensitivity) FLC kappa monomers and dimers; instead, Freelite detects only FLC lambda dimers, while N Latex FLC detects only FLC monomers. After DTT treatment, only the N Latex lambda still detects FLC with reduced protein thiols, while the reactivity of all other reagents is abolished. Conclusions Due to their different reactivity against FLC monomers and oligomers, the Freelite and N Latex FLC are calibrated against different components of their own calibrators, making the two reagents not equivalent. The redox status of FLC determines the immunoreactivity not only of FLC dimers, but also of the monomers.


Assuntos
Cadeias Leves de Imunoglobulina/análise , Automação , Western Blotting , Calibragem , Cromatografia em Gel , Dimerização , Eletroforese em Gel de Poliacrilamida , Humanos , Cadeias Leves de Imunoglobulina/química , Nefelometria e Turbidimetria/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...