Una causa olvidada de insuficiencia cardíaca / A forgotten cause of heart failure

Amyloidosis is a low-frequency disease that can cause compromise of different systems. We report a case of heart failure in an 81-year-old woman secondary to amyloidosis, in which the echocardiogram was a valuable diagnostic tool.

Amiloidosis AL: conceptos actuales / AL amyloidosis: current concepts

Las amiloidosis sistémicas constituyen un grupo de enfermedades con diversas etiologías, caracterizadas por la síntesis de proteínas con plegado defectuoso, capaces de agregarse y depositarse en el medio extracelular de diferentes órganos y tejidos, alterando su estructura y función. Se conocen más de 14 formas de amiloidosis sistémica, de las cuales la más frecuente es la amiloidosis AL, objeto de esta revisión, en la que las proteínas precursoras son cadenas ligeras de inmunoglobulina inestables, secretadas por un clon de células plasmáticas o, con menor frecuencia, por un linfoma linfoplasmocítico o de células del manto. La amiloidosis AL puede llevar a una amplia gama de manifestaciones clínicas y compromiso de órganos, como el corazón y el riñón. El reconocimiento temprano de la enfermedad y el diagnóstico oportuno son determinantes para mejorar la supervivencia de los pacientes. El tratamiento deberá ser individualizado de acuerdo con la condición de cada paciente, lo que hace necesaria una correcta clasificación de los individuos según su pronóstico. La terapia dirigida a la amiloidosis está enfocada esencialmente en disminuir el compromiso orgánico, y por ende, prolongar la supervivencia con mejoría en los síntomas. En esta revisión se discutirán aspectos importantes de la fisiopatología, epidemiología, manifestaciones clínicas, diagnóstico y tratamiento de la amiloidosis AL

Systemic amyloidosis constitutes a group of diseases with diverse etiologies characterized by the synthesis of proteins with defective folding, capable of aggregating and depositing in the extracellular matrix of different organs and tissues, altering their structure and function. More than 14 forms of systemic amyloidosis are known, of which the most frequent is AL amyloidosis, the subject of this review, in which the precursor proteins are unstable immunoglobulin light chains, secreted by a clone of plasma cells or, to a lesser extent, often due to lymphoplasmacytic or mantle cell lymphoma. AL amyloidosis can lead to a wide range of clinical manifestations and organ involvement, such as the heart and kidney. Early recognition of the disease and timely diagnosis are crucial to improve patient survival. Treatment should be individualized according to the condition of each patient, which requires a properly classification of individuals according to their prognosis. Amyloidosis-targeted therapy is essentially focused on reducing organ involvement, and therefore prolonging survival with improvement in symptoms. In this review, important aspects of the pathophysiology, epidemiology, clinical manifestations, diagnosis, and treatment of AL amyloidosis are discussed

Disruptive technologies for hemodialysis: medium and high cutoff membranes. Is the future now? / Tecnologias disruptivas para hemodiálise: membranas de ponto de corte médio e alto. O futuro é agora?

Abstract In the past decade, a new class of hemodialysis (HD) membranes (high retention onset class) became available for clinical use. The high cutoff (HCO) and the medium cutoff (MCO) membranes have wider pores and more uniformity in pore size, allowing an increased clearance of uremic toxins. Owing to the mechanism of backfiltration/internal filtration, middle molecules are dragged by the convective forces, and no substitution solution is needed. The HCO dialyzer is applied in septic patients with acute kidney injury requiring continuous kidney replacement therapy. The immune response is modulated thanks to the removal of inflammatory mediators. Another current application for the HCO dialyzer is in hematology, for patients on HD secondary to myeloma-kidney, since free light chains are more efficiently removed with the HCO membrane, reducing their deleterious effect on the renal tubules. In its turn, the MCO dialyzer is used for maintenance HD patients. A myriad of clinical trials published in the last three years consistently demonstrates the ability of this membrane to remove uremic toxins more efficiently than the high-flux membrane, an evolutionary disruption in the HD standard of care. Safety concerns regarding albumin loss as well as blood contamination from pyrogens in the dialysate have been overcome. In this update article, we explore the rise of new dialysis membranes in the light of the scientific evidence that supports their use in clinical practice.

Resumo Na última década, uma nova classe de membranas de hemodiálise (HD) (classe de início de alta retenção) tornou-se disponível para uso clínico. As membranas de ponto de corte alto (HCO) e ponto de corte médio (MCO) têm poros mais largos e maior uniformidade no tamanho dos poros, permitindo uma maior depuração de toxinas urêmicas. Devido ao mecanismo de retrofiltração/filtração interna, as moléculas médias são arrastadas pelas forças convectivas, não sendo necessária uma solução de substituição. O dialisador de HCO é aplicado em pacientes sépticos com lesão renal aguda que requerem terapia renal substitutiva contínua. A resposta imunológica é modulada graças à remoção de mediadores inflamatórios. Outra aplicação atual para o dialisador de HCO é em hematologia, para pacientes em HD secundária ao rim do mieloma, uma vez que as cadeias leves livres são removidas mais eficientemente com a membrana de HCO, reduzindo seu efeito deletério sobre os túbulos renais. Por sua vez, o dialisador de MCO é utilizado para pacientes em HD de manutenção. Uma miríade de ensaios clínicos publicados nos últimos três anos demonstra consistentemente a capacidade desta membrana de remover toxinas urêmicas de forma mais eficiente do que a membrana de alto fluxo, uma ruptura evolutiva no padrão de cuidado em HD. As preocupações de segurança em relação à perda de albumina, bem como a contaminação do sangue por pirogênios no dialisato foram superadas. Neste artigo de atualização, exploramos o surgimento de novas membranas de diálise à luz das evidências científicas que apoiam seu uso na prática clínica.

Cardiac magnetic resonance and amyloidosis: review / Ressonância magnética cardíaca e amiloidose: revisão

Amyloidosis is a disease caused by extracellular deposition of insoluble protein fibrils, that results in changes in tissue architecture and consequently modification of the organ structure. Cardiac involvement is common in amyloidosis. Two major types of systemic amyloidosis affect the myocardium ­ immunoglobulin light chain and transthyretin amyloidosis ­ each leading to different prognosis. Early detection and diagnosis of cardiac amyloidosis are the main objectives in the assessment of the disease. New techniques of magnetic resonance imaging have minimized the need for biopsies for the diagnosis. Late gadolinium enhancement technique, and more recently T1 mapping, have allowed a simplified evaluation of amyloid deposits and extracellular volume. The aim of this review was to describe basic concepts and updates of the use of magnetic resonance imaging for the diagnosis amyloidosis and evaluation of its severity

Sensibilidad diagnóstica de electroforesis de proteínas y cadenas livianas libres séricas en gammapatías monoclonales / Diagnostic accuracy of serum protein electrophoresis and free light chain measurements for monoclonal gammopathies

Background: International guidelines suggest a screening panel for monoclonal gammopathies that contains serum protein electrophoresis (SPE), free light chain (FLC) measurements and immunofixation. This combination provides the possibility of a timely accurate diagnosis. Aim: To evaluate the sensibility of a simple screening panel (SPE + FLC). Material and Methods: We analyzed 191 consecutive serum samples of patients with a suspected monoclonal gammopathy (MG). Results: Seventy five patients were diagnosed with MG. The sensitivity and specificity of the combination of SPE + FLC for the diagnosis of monoclonal gammopathy were 95% (95% confidence intervals 89-99) and 99% (95% confidence intervals 96-100), respectively. Conclusions: We were able to validate the international recommendations on the diagnostic accuracy of this simple combination of two tests in serum for monoclonal gammopathy.

Treatment of idiopathic light chain deposition disease: complete remission with bortezomib and dexamethasone / Tratamento da doença de depósito de cadeia leve idiopática: remissão completa com bortezomib e dexametasona

Abstract Light chain deposition disease (LCDD) is a rare clinical entity characterized by the deposition of light chain immunoglobulins in different tissues and primarily affects the kidneys, followed by the liver and heart. This disease often manifests as nephrotic syndrome with marked proteinuria and rapid deterioration of renal function. More than 50% of cases are secondary to multiple myeloma or other lymphoproliferative diseases, with a well-established treatment aimed at controlling the underlying disease. In rare cases, there is no detection of an associated hematological disease, referred to as idiopathic LCDD. In these cases, there is no evidence-based consensus on the therapeutic approach, and management is based on the clinical experience of reported cases. Here we report a case of idiopathic LCDD treated with bortezomib and dexamethasone with complete hematologic responses, significant reduction of proteinuria, and improved renal function.

Resumo A doença de deposição de cadeia leve (DDCL) é uma entidade clínica rara caracterizada pela deposição de cadeias leves das imunoglobulinas em diferentes tecidos e afeta principalmente os rins, seguido pelo fígado e coração. Manifesta-se frequentemente como síndrome nefrótica com proteinúria marcante e rápida deterioração da função renal. Mais de 50% dos casos são secundários ao mieloma múltiplo ou outras doenças linfoproliferativas, tendo seu tratamento bem estabelecido, voltado para o controle da doença de base. Em casos raros, não há detecção de uma doença hematológica associada, sendo referida como DDCL idiopática. Nestes casos, não há um consenso baseado em evidências sobre a abordagem terapêutica, tendo sua conduta baseada na experiência clínica dos casos relatados. Aqui, nós relatamos um caso de DDCL idiopática tratado com bortezomib e dexametasona atingindo resposta hematológica completa, redução significativa da proteinúria e recuperação da função renal.

Tres casos de mieloma múltiple de novo después de trasplante renal / Three cases of de novo multiple myeloma after kidney transplantation

RESUMEN La enfermedad renal asociada a cadenas ligeras es frecuente en el contexto de las gammapatías monoclonales, afecta los glomérulos o los túbulos renales, y su causa más común es el mieloma múltiple. Puede desarrollarse después de un trasplante renal por recurrencia de un mieloma múltiple ya existente, o puede ser de diagnóstico nuevo y presentarse con deterioro de la función renal y proteinuria. Siempre se requiere una biopsia renal para confirmar el diagnóstico.

ABSTRACT Light chain-associated kidney compromise is frequent in patients with monoclonal gammopathies; it affects the glomeruli or the tubules, and its most common cause is multiple myeloma. It may develop after a kidney transplant due to recurrence of a preexisting multiple myeloma or it can be a de novo disease manifesting as graft dysfunction and proteinuria. A kidney biopsy is always necessary to confirm the diagnosis.

Serum free light chain assays not total light chain assays are the standard of care to assess Monoclonal Gammopathies

Abstract The diagnosis of Multiple Myeloma is a challenge to the physician due to the non-specific symptoms (anemia, bone pain and recurrent infections) that are commonplace in the elderly population. However, early diagnosis is associated with less severe disease, including fewer patients presenting with acute renal injury, pathological fractures and severe anemia. Since 2006, the serum free light chain test Freelite® has been included alongside standard laboratory tests (serum and urine protein electrophoresis, and serum and urine immunofixation) as an aid in the identification of monoclonal proteins, which are a cornerstone for the diagnosis of Multiple Myeloma. The serum free light chain assay recognizes the light chain component of the immunoglobulin in its free form with high sensitivity. Other assays that measure light chains in the free and intact immunoglobulin forms are sensitive, but unfortunately, due to the nomenclature used, these assays (total light chains) are sometimes used in place of the free light chain assay. This paper reviews the available literature comparing the two assays and tries to clarify hypothetical limitations of the total assay to detect Multiple Myeloma. Furthermore, we elaborate on our study comparing the two assays used in 11 Light Chain Multiple Myeloma patients at presentation and 103 patients taken through the course of their disease. The aim of this article is to provide a clear discrimination between the two assays and to provide information to physicians and laboratory technicians so that they can utilize the International Myeloma Working Group guidelines.

Amiloidosis por cadenas livianas de inmunoglobulina con compromiso gástrico al debut: revisión de la literatura basada en un caso clínico / Gastric AL amyloidosis as initial manifestation: literature review from a case report

Systemic amyloidosis comprises a group of diseases characterized by low molecular weight subunit protein deposit in organs, including the gastrointestinal tract. The most frequent clinical manifestations are gastrointestinal bleeding, malabsorption syndrome, protein-losing enteropathy and chronic intestinal dysmotility. The diagnosis is confirmed with gastrointestinal tissue biopsy positive to Congo red stain or recognizing the amyloid fibrils by electron microscopy. The treatment is based in the management of gastrointestinal symptoms and chemotherapeutic drugs, including melphalan and prednisone or cyclophosphamide, bortezomib and prednisone. The bone marrow transplant is reserved for 70-year-old patients or younger without advanced comorbidities. We present a case of a patient with weight loss, anorexia, nausea and early satiety.

La amiloidosis sistémica a un conjunto de enfermedades caracterizadas por el depósito de subunidades fibrilares proteicas de bajo peso molecular en órganos, incluyendo el sistema digestivo. Sus manifestaciones clínicas más frecuentes son la hemorragia digestiva, síndrome malabsortivo, gastro-enteropatía perdedora de proteínas y dismotilidad gastrointestinal crónica. El diagnóstico se confirma con una biopsia de tejido gastrointestinal positiva a tinción rojo Congo o la visualización de fibrillas de amiloide mediante microscopia electrónica. El tratamiento está basado el manejo de los síntomas gastrointestinales y el oncológico, donde destacan esquemas quimioterapéuticos que incluyen melfalan y prednisona o ciclofosfamida, bortezomib y prednisona. El trasplante de médula ósea está reservado a pacientes menores de 70 años sin comorbilidades avanzadas. Presentamos en este artículo el caso de un paciente con baja de peso, anorexia, náuseas y saciedad precoz.

Syndrome in Question

Immunoglobulin light chain amyloidosis is the most common acquired systemic amyloidosis. Its presentation is often insidious and progressive, which may delay diagnosis. The authors describe a rare case of immunoglobulin light chain amyloidosis in a 34-year-old man with scleroderma-like manifestation substantiated by multifarious laboratory investigations and the histopathologic feature of involved skin lesions stained with Congo red and crystal violet. This helps to maintain a high clinical suspicion of the disease when confronting similar skin presentation.

Utilidad del ensayo de cadenas livianas libres en suero en el manejo de gammapatías monoclonales: diagnóstico, pronóstico y monitoreo / Usefulness of serum free light chain testing in the handling of monoclonal gammapathies: diagnosis, prognosis and monitoring

El ensayo de cadenas livianas libres en suero cuantifica los niveles de κ y λ libres. Existen tres indicaciones principales para la medición de cadenas livianas libres en el manejo de pacientes con mieloma múltiple y enfermedades relacionadas. Primero, en el contexto del diagnóstico, donde en combinación con la electroforesis de proteínas en suero y la inmunofijación en suero proporcionan el esquema de tamizaje de mayor sensibilidad, eliminando la necesidad de analizar la orina de 24 horas. Segundo, los valores basales de cadenas livianas libres en suero han mostrado tener valor pronóstico para la mayoría de las gammapatías monoclonales. Tercero, el ensayo de cadenas livianas libres en suero permite un monitoreo cuantitativo y sensible en pacientes con presentación oligosecretora de la enfermedad, incluyendo la AL amiloidosis y cerca del 70% de los pacientes históricamente denominados no secretores. Esta revisión tiene por objeto actualizar la información sobre las aplicaciones de esta importante prueba...

Distribución de tipos de paraproteínas en una muestra de enfermos con mieloma múltiple / Distribution of types of paraproteins in a sample of patients with multiple myeloma

Introducción: el mieloma múltiple (MM) es una enfermedad caracterizada por una proliferación monoclonal de inmunoglobulinas que representa aproximadamente el 15 por ciento de las hemopatías malignas. Métodos: se realizó un estudio de la distribución de las clases, sub clases y tipos de cadenas ligeras de inmunoglobulinas en 285 enfermos con el diagnóstico de MM. Se emplearon tres métodos: electroforesis de proteínas en suero para la detección de la inmunoglobulina monoclonal o paraproteína, electroforesis de inmunofijación y doble inmunodifusión para identificar las clases, sub clases y tipo de cadenas ligeras. Resultados: se encontraron 206 enfermos (72.28 por ciento) con MM IgG; 73 (25.62 por ciento) con MM IgA y 6 (2.1 por ciento) con MM IgM. La distribución de sub clases de IgG fue: 130 casos (63.11 por ciento) IgG1, 43 (20.87 por ciento) IgG2, 21 (10.19 porciento) IgG3 y 12 (5.83 por ciento) IgG4; y la de sub clases de IgA fue de 59 enfermos (80.82 por ciento) IgA1 y 14 (19.18 por ciento) IgA2. Del total de enfermos 187 (65.61 por ciento) mostraron cadenas ligeras tipo kappa y 98 (34.38 por ciento) tipo lambda. Conclusiones: los datos obtenidos en nuestro estudio permitieron identificar la frecuencia de distribución de las clases, subclases y cadenas ligeras en una muestra de enfermos con MM

Introduction: multiple mieloma (MM) is a disease characterized by a monoclonal proliferation of immunoglobulins representing approximately 15 percent of malignant hemopathies. Methods: the distribution of classes, subclasses and light chains of monoclonal immunoglobulins was studied in 285 patients with MM. Three methods were used: serum protein electrophoresis for the detection of monoclonal immunoglobulins or paraproteins, immunofixation electrophoresis and double immunodiffusion to identify classes, subclasses and light chain types. Results: 206 patients (72.28 percent) with IgG MM, 73 (25,62 percent) with IgA MM, and 6 (2,1 percent) with IgM MM were found. The distribution of IgG subclasses was: 130 cases (63,11 percent) IgG1; 43 (20,87 percent) IgG2; 21 (10,19 percent) IgG3: and 12 (5,83 percent) IgG4. Distribution of IgA subclasses was: 59 patients (80,82 percent) IgA1 and 14 (19,18 percent) IgA2; 187 patients (65,62 percent) showed kappa light chains and 98 (34,38 percent) were lambda. Conclusions: the data obtained in our study allowed us to identify the frequency of distribution of classes, subclasses and light chains in a sample of patients with MM

Enfermedad renal por depósito idiopático de cadenas livianas: Caso clínico / Kidney involvement in idiopathic light chain disease: Report of one case

Idiopathic Light Chain disease (ILCD) is a systemic disease characterized by a deposit in different organs of light chain monoclonal immunoglobulins, produced by an abnormal clone ofB cells. It is usually found in the course ofa plasma cell dyscrasia and in other lymphoproliferative alterations; however it may occur in absence of any hematologic disease and is denominated as idiopathic. We report a 51-year-old mole admitted to the hospital due to anasarca. Laboratory evaluation showed a serum creatinine of 1.4 mg/dl, a serum albumin of1.6 g/dl, a serum cholesterol of 687 mg/dl and a proteinuria of 5.3 g/day Light chains with a predominance of a monoclonal component were identified in urinary proteins by electrophoresis and kappa chains were identified by immunofixation. A renal biopsy showed a diffuse nodular glomerulopathy with a 35% tubular atrophy and interstitial sclerosis. Electrón microscopy confirmed light chain deposition. The bone marrow biopsy showed a myeloid hyperplasia. Thepatient was initially treated with methylprednisolone and plasmapheresis with a reduction in serum creatinine and disappearance of urinary kappa component. Albuminuriapersisted and a malnutrition-inflammatory complex syndrome was diagnosed. Hemodialysis with ultrafiltration was started along with cyclophosphamide. Thepatient receivedhemodialysisforsixmonths and continued with methylprednisolone.

Immunoglobulin light chain amyloidosis associated with multiple myeloma in a young patient: a case report / Amiloidosis de cadenas ligeras de asociada con mieloma múltiple en un paciente joven: reporte de un caso

The authors present an uncommon case of systemic amyloidosis associated with multiple myeloma in a 35-year old woman. Systemic amyloidosis commonly presents in association with clonal plasma cell proliferative disorders, and less frequently as secondary or of a hereditary origin. Amyloidosis is usually associated with multiple myeloma in older patients and frequently has an unfavourable prognosis.

Los autores presentan aquí un caso raro de amiloidosis sistémica asociado con mieloma múltiple en una mujer de 35 años de edad. La amiloidosis sistémica normalmente se presenta asociada con desórdenes proliferativos de las células plasmáticas clonales, y con menor frecuencia con origen secundario o hereditario. Amiloidosis se asocia normalmente con el mieloma múltiple en pacientes de mayor edad y frecuentemente tiene una prognosis desfavorable.

Nefropatía no amiloidea por depósito de inmunoglobulinas monoclonales: A propósito de un caso de enfermedad idiopática por depósito de cadenas ligeras / Nonamyloidotic glomerular disease caused by light chain deposits: a case report

La nefropatía de las gammapatías monoclonales es debida, principalmente, al depósito de cadenas ligeras. Las enfermedades renales paraproteinémicas son lesiones asociadas con depósitos de inmunoglobulinas intactas o fragmentos de inmunoglobulinas (cadenas pesadas y cadenas ligeras). La enfermedad por depósito de cadenas ligeras es una condición rara, caracterizada por el depósito de cadenas monoclonales ligeras en muchos órganos y, en el riñón, predominantemente, en glomérulos y membranas basales tubulares. La enfermedad está frecuentemente asociada con alteraciones linfoproliferativas y la mayoría de casos son causados por depósito de cadenas ligeras kappa. Aunque se presenta sobre todo en cuadros malignos, en ocasiones, no se detecta enfermedad hematológica y se denomina idiopática o primaria. Suele manifestarse como una insuficiencia renal grave con proteinuria nefrótica, no tiene tratamiento claramente establecido y el pronóstico es malo. Se describen las características clínicas e histológicas del primer caso informado en Colombia de nefropatía por depósito de cadenas ligeras, diagnosticado en el contexto de una enfermedad renal paraproteinémica sin datos de malignidad.

The nephropathy of monoclonal gammopathies is principally caused by light chain deposits of fragmented immunoglobins. Paraprotein-related renal diseases are associated with such deposits of intact (heavy chain) or fragmentary (light chain) immunoglobins. A condition of pathological light chain deposits is rare and characterized by deposits of fragments of monoclonal immunoglobulins in many organs. Renal deposits occur primarily in glomeruli and tubular basement membranes. This disease is frequently associated with lymphoproliferative disorders. The majority of cases are caused by deposits of kappa light chains. Whereas this disease is most frequently associated with hematologic malignancies, occasionally a case occurs without detectable hematological pathologies; these cases are called idiopathic or primary. They usually manifest themselves as severe renal insufficiencies with nephrotic-range proteinuria. No treatment regime has been clearly established and the prognosis is poor. Herein, the clinical and histological characteristics are described regarding the first case in Colombia of light chain deposit disease without symptoms of malignancy.

Pesquisa do rearranjo dos genes das cadeias leve e pesada de imunoglobulina nos processos linfoproliferativos cutâneos de células B / Detection of immunoglobulin light and heavy chain genes rearrangements in cutaneous B cell lymphoproliferative infiltrates

INTRODUÇÃO: O diagnóstico diferencial dos processos linfoproliferativos cutâneos de célula B permanece um desafio para patologistas, dermatologistas, hematologistas e oncologistas, apesar dos recentes avanços imunoistoquímicos e moleculares. OBJETIVO: Este trabalho avaliou o auxílio diagnóstico e as limitações da pesquisa da clonalidade utilizando a biologia molecular nos linfomas primários cutâneos de célula B e pseudolinfomas de células B, assim como a relevância da análise dos dados em conjunto com informações clínicas, histológicas e imunoistoquímicas. MÉTODOS: O estudo incluiu 31 casos de processos linfoproliferativos cutâneos de célula B classificados à histologia e imunoistoquímica como 14 linfomas, 6 pseudolinfomas e 11 casos inconclusivos. A pesquisa da clonalidade foi realizada em todos os casos por meio da pesquisa do rearranjo dos genes da cadeia leve kappa e pesada utilizando o método de PCR. RESULTADOS: Os resultados confirmaram monoclonalidade em 61,5% dos linfomas. Em adição, o método evidenciou monoclonalidade em 20% dos casos inconclusivos à avaliação histológica e imunoistoquímica. A pesquisa do rearranjo dos genes de cadeia leve kappa resultou mais contributiva em relação à pesquisa do rearranjo dos genes da cadeia pesada. CONCLUSÕES: Estes resultados demonstraram a utilidade do método no auxilio diagnóstico dos linfomas cutâneos. A maior contribuição no estudo da clonalidade dos processos linfoproliferativos cutâneos de células B, através da pesquisa do rearranjo dos genes de cadeia leve kappa em associação com a pesquisa do rearranjo dos genes de cadeia pesada, sugeriu a necessidade da utilização conjunta das duas técnicas para maior acurácia diagnóstica nestes casos.

INTRODUCTION: The differential diagnosis of the lymphoproliferative B-cell infiltrates remains an important challenge for pathologists, dermatologists, hematologists and oncologists, despite the recent advances in immunohistochemical and molecular techniques. OBJECTIVES: This study has evaluated the diagnostic aid and the limitations of the clonality analysis using molecular biology in cutaneous B-cell lymphomas and pseudolymphomas, as well as the relevance of this analysis when combined with clinical, histological and immunohistochemical data. METHODS: The study covered 31 cases of cutaneous lymphoproliferative B-cell infiltrates classified by histological and immunohistochemical characteristics as 14 lymphomas, 6 pseudolymphomas and 11 non-conclusive cases. The clonality analysis was performed in all cases using PCR to detect the pattern of immunoglobulin light kappa and heavy chains gene rearrangements. RESULTS: The results have confirmed monoclonality in 61,5% of lymphomas. In addition, the method showed monoclonality in 20% of the cases previously classified as a non-conclusive through histological and immunohistochemical evaluation. CONCLUSION: These results highlight the importance of the PCR clonality analysis as an ancillary diagnostic tool in cutaneous lymphoma. The research of the immunoglobulin light kappa gene rearrangement was more efficient resulting in a higher rate of monoclonality detection when compared to the heavy chain analysis. Nevertheless, the use of both protocols improves the sensitivity of the method.

Anemia crônica e glomerulopatia secundárias à Doença de Depósito das Cadeias Leves / Chronic anemia and glomerulopathy secondary to Light-chain Deposition Disease

Os autores relatam o caso de uma paciente do sexo feminino, 65 anos de idade, internada com anemia de longa evolução que se associou posteriormente a uma glomerulopatia manifestada por proteinúria, cilindrúria e perda de função renal. As cadeias leves no plasma e na urina estavam elevadas, sobretudo a fração kappa e uma biópsia renal estudada por imunofluorescência e microscopia eletrônica confirmou o diagnóstico de Doença de Depósito das Cadeias Leves. A nefropatia de cadeia leve ocorre pela superprodução de cadeia leve de imunoglobulina produzida por linfócitos B com deposição nas membranas tubulares e no glomérulo.

The autorpresent a case of a 65 year-old female patient, with chronic anemia associated with glomerulopathy manifested as proteinuria, cylindruria and renal failure. There were high serumand urinary levels of light chains and the diagnosis wasperformed by renal biopsy, examined using immunofluorescenceand by electron microscopy that showed light chain paraproteins.Nephropathy of light-chain deposition disease occurs due to anover-production of light chains from immunoglobulins producedby B lymphocytes with a deposit in tubular and glomerularmembranes.

Nephrotoxicity of human Bence Jones protein in rats: proteinuria and enzymuria profile

The effect of intravenous administration of 80 mg purified human Bence Jones protein twice weekly for 5 weeks was investigated in male Wistar rats (N = 7; 2 months old). A state of immunological tolerance was demonstrated by the absence of a B-cell response (plaque-forming cells and hemagglutination titers) and by the absence of detectable antigen or antibody deposition in glomeruli, as indicated by light and electron microscopy. No rise in blood urea level was detected (33.9 +/- 4.3 vs 32.8 +/- 1.3 mg per cent ). There was an increase in proteinuria (5.3 +/- 0.9 vs 32.8 +/- 4.0 mg/day), mainly due to Bence Jones protein excretion (0 vs 29.2 +/- 5.2 mg/day), with a slight but significant increase in albuminuria (0.2 +/- 0.1 vs 1.0 +/- 0.2 mg/day). There was a significant increase of lysosomal N-acetyl-beta-D-glucosaminidase in the urine (6.1 +/- 1.3 vs 72.7 +/- 18.8 mU/mg in creatinine). Lysosomal accumulation of Bence Jones protein in proximal tubular cells was evidenced by immunoelectronmicroscopy with protein A-gold. These results clearly showed proximal tubular dysfunction induced by chronic Bence Jones protein administration, without interference of autologous immune response as demonstrated by immunological state of tolerance

Propuesta de caracterización y tipificación de proteínas monoclonales aplicable al laboratorio clínico / Proposal of characterization and typification of monoclonal proteins applicable to clinical laboratory

En el presente trabajo se incorporan y ordenan procedimientos para obtener la mayor información posible a nivel laboratorio clínico en la indagación de proteínas "M" y la definición de su clase (cadenas pesadas) y tipo (cadenas livianas). Se propone una secuencia de las siguientes técnicas: electroforesis, inmunoelectroforesis, inmunofijación, inmunodifusión radial cuantitativa, tratamientos despolimerizantes e inmunosustracción. La inmunosustracción, descripta por W. A. White y col., consiste en la remoción de la inmunoglobulina en estudio mediante un antisuero específico en presencia de polietilenglicol, separación del inmunocomplejo precipitado y posterior evaluación del sobrenadante mediante inmunofijación; se identifica la cadena liviana que pertenece a la inmunoblobulina sustraída por su ausencia al fijar con el antisuero correspondiente. Es particularmente útil cuando se desea establecer la correspondencia liviana/pesada en presencia de bandas homogéneas múltiples, identificar bandas menores enmascaradas en un fondo policlonal y excluir la presencia coincidente de cadenas livianas libres. Se aconseja incorporar el tratamiento despolimerizante con 2-mercaptoetanol previamente a la cuantificación de IgM por inmunodifusión radial ya que la comparación previa entre controles tratados y no tratados reveló una diferencia muy significativa cuando se analizó mediante contraste de diferencias entre pares homólogos (n = 12, test t = 37,2 p <0,01)