Valor diagnóstico de la electroforesis de proteínas y cadenas ligeras libres en suero en el mieloma múltiple / Diagnostic value of serum protein electrophoresis and free light chains in the multiple myeloma's diagnosis

RESUMEN Fundamento: La electroforesis de proteínas y las cadenas ligeras libres en suero son técnicas utilizadas en el diagnóstico del mieloma múltiple. Sin embargo, la utilidad diagnóstica de ambas pruebas puede variar según el método empleado y condiciones reales del medio donde se realicen. Objetivo: Determinar el valor diagnóstico de la electroforesis de proteínas y de las cadenas ligeras libres en suero en el mieloma múltiple. Metodología: Se realizó un estudio retrospectivo de los parámetros electroforesis de proteínas en suero y cadenas ligeras libres en suero a 43 pacientes con diagnóstico de mieloma múltiple por evaluación de la médula ósea. La electroforesis de proteínas se realizó por el método convencional de separación de proteínas sobre papel de acetato de celulosa y para las cadenas ligeras libres se aplicó un ensayo inmunoturbidimétrico en el que se usó un analizador químico (Cobas 311). Se calcularon 7 parámetros que evaluaron la exactitud diagnóstica. Resultados: Todos los parámetros que evaluaron la exactitud diagnóstica estuvieron dentro de los intervalos de confianza en ambas pruebas. Conclusiones: La electroforesis de proteínas y las cadenas ligeras libres en suero son ensayos de gran utilidad en el diagnóstico del mieloma múltiple y se deben utilizar en conjunto para la mayor captación posible de casos.

ABSTRACT Background: Protein electrophoresis and serum free light chains are techniques used in the diagnosis of multiple myeloma. However, the diagnostic utility of both tests may vary according to the method used and the actual conditions of the environment where they are performed. Objective: To determine the diagnostic value of protein electrophoresis and serum free light chains in multiple myeloma. Methodology: A retrospective study of serum protein electrophoresis parameters and serum free light chains was conducted in 43 patients diagnosed with multiple myeloma by bone marrow evaluation. Protein electrophoresis was completed by the conventional method of protein separation on cellulose acetate paper and for free light chains an immunoturbidimetric assay was applied in which a chemical analyzer (Cobas 311) was used. Seven parameters were calculated to evaluate diagnostic accuracy. Results: All parameters assessing diagnostic accuracy were within confidence intervals in both tests. Conclusions: Protein electrophoresis and serum free light chains are very useful assays in the diagnosis of multiple myeloma and should be used in conjunction for the highest possible approval of cases.

Valor diagnóstico de la electroforesis de proteínas y cadenas ligeras libres en suero en el mieloma múltiple / Diagnostic value of serum protein electrophoresis and free light chains in the multiple myeloma's diagnosis

Fundamento: La electroforesis de proteínas y las cadenas ligeras libres en suero son técnicas utilizadas en el diagnóstico del mieloma múltiple. Sin embargo, la utilidad diagnóstica de ambas pruebas puede variar según el método empleado y condiciones reales del medio donde se realicen. Objetivo: Determinar el valor diagnóstico de la electroforesis de proteínas y de las cadenas ligeras libres en suero en el mieloma múltiple. Metodología: Se realizó un estudio retrospectivo de los parámetros electroforesis de proteínas en suero y cadenas ligeras libres en suero a 43 pacientes con diagnóstico de mieloma múltiple por evaluación de la médula ósea. La electroforesis de proteínas se realizó por el método convencional de separación de proteínas sobre papel de acetato de celulosa y para las cadenas ligeras libres se aplicó un ensayo inmunoturbidimétrico en el que se usó un analizador químico (Cobas 311). Se calcularon 7 parámetros que evaluaron la exactitud diagnóstica. Resultados: Todos los parámetros que evaluaron la exactitud diagnóstica estuvieron dentro de los intervalos de confianza en ambas pruebas. Conclusiones:La electroforesis de proteínas y las cadenas ligeras libres en suero son ensayos de gran utilidad en el diagnóstico del mieloma múltiple y se deben utilizar en conjunto para la mayor captación posible de casos [AU]

Two Cases of Crystal-storing Histiocytosis Diagnosed by Morphology, Immunohistochemistry, and Ultrastructural Examination.

Crystal-storing histiocytosis (CSH) is a non-neoplastic histiocytic proliferation containing crystalline material, usually associated with an underlying lymphoproliferative or plasmacytic disorder. The crystalline structures are typically derived from kappa light chain immunoglobulins. The lesions of CSH are comprised of sheets of histiocytes with abundant eosinophilic cytoplasm containing variably prominent, elongated crystals. This rare phenomenon is important to recognize, as it is known to morphologically obscure an underlying neoplasm. Histologically, the cells of CSH may closely mimic Gaucher cells, as well as the "pseudo-Gaucher" cells sometimes encountered in chronic myeloid leukemia. The distinction between the cells of CSH and that of histologic mimics may be made more definitively through the use of electron microscopy, as the crystalline inclusions seen in CSH display characteristic size, shape, and localization within the cells. Here, we report 2 rare cases of CSH diagnosed by morphology, immunohistochemistry, and ultrastructural examination. The first case presented was diagnosed concurrently with plasma cell myeloma, and the second case discussed was diagnosed in association with marginal zone lymphoma.

Regressão do depósito amiloide e normalização da função ventricular em paciente com amiloidose de cadeias leves tipo Kappa / Regression of amyloid deposit and normalization of ventricular function in a patient with Kappa-type light chain amyloidosis

INTRODUÇÃO: A amiloidose por depósito de cadeias leves (AL) é reconhecida como um tipo de amiloidose associado a quadro clínico devastador e prognóstico sombrio se diagnosticada tardiamente. É por este motivo considerada uma urgência médica, pelo fato do tratamento precoce modificar radicalmente a evolução. A presença de sintomas graves de cardiopatia geralmente empobrece o prognóstico e contraindica o transplante de medula óssea (MO). Descrevemos um caso de evolução favorável de amiloidose AL com tratamento medicamentoso. Caso Clínico: paciente de 83 anos, hígido, realizando atividade física intensa, apresentou subitamente piora significativa da capacidade funcional, evoluindo para dispneia aos pequenos esforços e em repouso, em 3 meses de evolução. Foi internado para compensação do quadro em UTI por duas ocasiões, em anasarca, necessitando drogas vasoativas. Realizou ecocardiograma que evidenciou espessura de septo de 19 mm e parede posterior de 17mm, fração de ejeção de 62%, relação E/e'19, e eletrocardiograma com ritmo sinusal e padrão de baixa voltagem no plano frontal. Relação kappa/lambda de 94,6 (valor de referência de 0,26 a 1,65). Foi submetido a biopsia de MO e de gordura abdominal, a imunohistoquímica da MO evidenciou infiltrado intersticialde células plasmocitárias monoclonais para cadeias leves kappae a de gordura abdominal corou com vermelho Congo. Foi submetido aovesquema CyBorD por 1 mês (Ciclofosfamida, Bortezomibe e Dexametasona) Ecocardiograma realizado após 1 ano, evidenciou diminuição significativa da espessura de paredes (septo de 13mm e parede posterior de 12mm). Em 1 ano e 6 meses, o ecocardiograma era normal, com espessura de septo e de parede posterior de 10mm, relação E/e'de 10. COMENTÁRIOS: O diagnóstico de amiloidose de cadeias leves é realizado de forma relativamente simples, com a dosagem da relação kappa/lambda quando esta está muito elevada. Neste caso, a evolução foi muito favorável, com regressão da cardiopatia provavelmente pelo diagnóstico ter sido precoce. O ecocardiograma foi o elemento determinante do diagnóstico e evolução. CONCLUSÃO: A amiloidose de cadeias livres leves tipo Kappa pode ter uma evolução extremamente favorável quando o diagnóstico é feito precocemente, portanto o reconhecimento desta patologia é fundamental para a melhora do prognóstico.

Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires.

BACKGROUND: The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS). METHODS: CSF and serum samples from CIS, MS and other neurological non-MS disease were collected between 2015 and 2017. FLC concentrations were measured using immunoassay Freelite™. Results were correlated with the patients' diagnoses and ROC curve analysis was used to determine accuracy. In CIS patients, analysis of FLC were compared in CIS converters vs. non-converter during follow-up. RESULTS: In the MS group (n = 41), the optimal cut-off for KFLC determined was 7 mg/L, with a diagnostic sensitivity and specificity of 95% and 97%, respectively. The optimal cut-off for LFLC was 0.7 mg/L, with a diagnostic sensitivity and specificity of 71% and 81%, respectively. 36 CIS patients were included; mean follow-up time was 28 ± 9 months, and 22 (61.1%) patients converted to MS. The median concentration of CSF K and LFLCs at CIS diagnosis was slightly higher in CIS-converters compared to non-converters, but this did not reach statistical significance (KFLC: median 7 ± 5.3 mg/L vs. 5 ± 2.3 mg/L, p = 0.11; LFLC 0.7 ± 0.33 mg/L vs. 0.5 ± 0.23 mg/L p = 0.16). A strong correlation was observed between the concentration of K and L FLCs at diagnosis and the change in PBVC during follow-up (r = 0.72 and r = 0.65, respectively). CONCLUSION: KFLCs have a high sensitivity and specificity for the diagnosis of MS. FLC concentrations at CIS diagnosis were not significantly higher in CIS-converters.

A B-Cell Superantigen Induces the Apoptosis of Murine and Human Malignant B Cells.

B-cell superantigens (Sags) bind to conserved sites of the VH or VL regions of immunoglobulin molecules outside their complementarity-determining regions causing the apoptosis of normal cognate B cells. No attempts to investigate whether B-cell Sags are able to induce the apoptosis of cognate malignant B cells were reported. In the present study we show that protein L (PpL), secreted by Finegoldia magna, a B-cell Sag which interacts with κ+ bearing cells, induces the apoptosis of murine and human κ+ lymphoma B cells both in vitro and in vivo. Apoptosis was not altered by caspase-8 inhibitor. No alterations in the levels of Bid, Fas and Fas-L were found suggesting that PpL does not activate the extrinsic pathway of apoptosis. The involvement of the intrinsic pathway was clearly indicated by: i) alterations in mitochondrial membrane potential (ΔΨm) both in murine and human lymphoma cells exposed to PpL; ii) decreased levels of apoptosis in the presence of caspase-9 inhibitor; iii) significant increases of Bim and Bax protein levels and downregulation of Bcl-2; iv) the translocation from the cytoplasm to the mitochondria of Bax and Bim pro-apoptotic proteins and its inhibition by caspase-9 inhibitor but not by caspase-8 inhibitor and v) the translocation of Bcl-2 protein from the mitochondria to the cytosol and its inhibition by caspase-9 inhibitor but not by caspase-8 inhibitor. The possibility of a therapeutic use of Sags in lymphoma/leukemia B cell malignancies is discussed.

Stability engineering of anti-EGFR scFv antibodies by rational design of a lambda-to-kappa swap of the VL framework using a structure-guided approach.

Phage-display technology facilitates rapid selection of antigen-specific single-chain variable fragment (scFv) antibodies from large recombinant libraries. ScFv antibodies, composed of a VH and VL domain, are readily engineered into multimeric formats for the development of diagnostics and targeted therapies. However, the recombinant nature of the selection strategy can result in VH and VL domains with sub-optimal biophysical properties, such as reduced thermodynamic stability and enhanced aggregation propensity, which lead to poor production and limited application. We found that the C10 anti-epidermal growth factor receptor (EGFR) scFv, and its affinity mutant, P2224, exhibit weak production from E. coli. Interestingly, these scFv contain a fusion of lambda3 and lambda1 V-region (LV3 and LV1) genes, most likely the result of a PCR aberration during library construction. To enhance the biophysical properties of these scFvs, we utilized a structure-based approach to replace and redesign the pre-existing framework of the VL domain to one that best pairs with the existing VH. We describe a method to exchange lambda sequences with a more stable kappa3 framework (KV3) within the VL domain that incorporates the original lambda DE-loop. The resulting scFvs, C10KV3_LV1DE and P2224KV3_LV1DE, are more thermodynamically stable and easier to produce from bacterial culture. Additionally, C10KV3_LV1DE and P2224KV3_LV1DE retain binding affinity to EGFR, suggesting that such a dramatic framework swap does not significantly affect scFv binding. We provide here a novel strategy for redesigning the light chain of problematic scFvs to enhance their stability and therapeutic applicability.

Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia

Hepatitis C virus (HCV) infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC) of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p = 0.001 and p = 0.003, respectively), but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p > 0.05). The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p = 0.004). Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC), predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation.

Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia.

Hepatitis C virus (HCV) infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC) of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p=0.001 and p=0.003, respectively), but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p>0.05). The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p=0.004). Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC), predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation.

Nested polymerase chain reaction amplification and sequencing analysis of the light-chain and heavy-chain variable regions in the influenza A H1N1 virus hemagglutinin monoclonal antibody gene.

The nested polymerase chain reaction (PCR) method was used for the amplification of the influenza A H1N1 virus hemagglutinin monoclonal antibody light-chain and heavy-chain genes. Sequence analysis of the obtained genes was then used to identify common cloning methods of the mouse immunoglobulin-kappa (Igκ) light-chain and heavy-chain variable gene regions. Twenty-two pairs of amplification primers for the mouse Igκ light-chain and heavy-chain variable gene regions were designed, and 6 mouse anti-human H1N1 influenza virus hemagglutinin monoclonal antibody light-chain and heavy-chain variable gene regions were cloned and sequenced. Comparative analysis was conducted between our results and the mouse Ig sequences published in the National Center of Biotechnology Information (NCBI). The nested PCR method effectively avoided cloning the pseudogenes of the monoclonal antibody, and the amino acid sequence obtained was consistent with the characteristics of the mouse Ig variable region. A general method of cloning the mouse Ig light-chain and heavy-chain variable gene regions was established, which provides a basis for further cloning of mouse monoclonal antibody variable gene regions. This study also provides data for further studies of H1N1 influenza virus hemagglutinin antibody binding sites.

IGKC and FcγR genotypes and humoral immunity to HER2 in breast cancer.

Immunoglobulin κ constant (IGKC) gene has recently been identified as a strong prognostic marker in several human solid tumors, including breast cancer. Although the mechanisms underlying the IGKC signature are not yet known, identification of tumor-infiltrating plasma cells as the source of IGKC expression strongly suggests a role for humoral immunity in breast cancer progression. The primary aim of the present investigation was to determine whether the genetic variants of IGKC, KM (κ marker) allotypes, are risk factors for breast cancer, and whether they influence the magnitude of humoral immunity to epidermal growth factor receptor 2 (HER2), which is overexpressed in 25-30% of breast cancer patients and is associated with poor prognosis. Using a matched case-control design, we genotyped a large (1719 subjects) study population from Japan and Brazil for KM alleles. Both cases and controls in this study population had been previously characterized for GM (γ marker) and Fcγ receptor (FcγR) alleles, and the cases had also been characterized for anti-HER2 antibodies. Conditional logistic regression analysis of the data showed that KM1 allele additively contributed to the risk of breast cancer in the Japanese subjects from Nagano: Compared to KM3 homozygotes, KM1 homozygotes were almost twice as likely to develop breast cancer (OR=1.77, CI 1.06-2.95). Additionally, KM genotypes-individually and in particular epistatic combinations with FcγRIIa genotypes-contributed to the magnitude of anti-HER2 antibody responsiveness in the Japanese patients. This is the first report implicating KM alleles in the immunobiology of breast cancer.

Poor performance of the total kappa/lambda light chain quantification in the diagnosis and follow-up of patients with multiple myeloma.

BACKGROUND: The gold standard for paraproteinemia screening in plasma cell disorders has been serum protein electro- phoresis (SPE) with immunofixation electrophoresis (IFx); serum total and free light chain quantifications have also been used. OBJECTIVE: To define the role of SPE, IFx and serum total light chain (sLC) determinations in patients with multiple myeloma (MM), both at diagnosis and at maximum response during treatment follow-up. MATERIAL AND METHODS: These serological studies were performed in a group of 62 patients with MM at diagnosis, and in a subset of 29 patients at the point of maximum response to treatment. RESULTS: At diagnosis, we found an abnormal SPE in 58%, an abnormal IFx in 92% and an abnormal sLC in 45% of the 62 patients; 64% had simultaneously abnormal results in all three serological studies. IFx alone proved to be the most sensitive of all three assays, followed by SPE, which was redundant in most instances with sLC and IFx. At maximum response, the abnormal SPE normalized in 7 cases, the abnormal IFx in 7 cases and the abnormal sLC in 7 cases. There were 12 instances in which an abnormal IFx was found despite normal sLC, and one case in which a normal IFx was found in the presence of abnormal sLC. The association between IFx and sLC was highly significant (r = 0.9274611, p < 0.000001), despite instances where a positive result for IFx was associated to a normal sLC. CONCLUSION: All three serological methods should ideally be simultaneously performed in patients with MM both at diagnosis and throughout therapy. In this series, the total sLC assay was not more sensitive than IFx neither at diagnosis nor during follow-up.

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(AU)

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(AU)

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

Serum free light chains and post-transplant lymphoproliferative disorder in patients with renal transplant.

The aim of the present study was to determine whether there is an association between serum free light chains (sFLC) quantification and the development of post-transplant lymphoproliferative disorder (PTLD), using serum samples from a nested case-control cohort of patients with renal transplant. Ten new cases of PTLD and 46 controls were enrolled. Additional comparison groups consisted of five human immunodeficiency virus (HIV)-infected individuals, five with untreated Hodgkin lymphoma and six normal individuals. Serum κ and λ FLC concentrations were measured by nephelometry and compared with reference ranges (normal and renal ranges). κ and/or λ were above the normal range in 90% of cases and in 65% of matched controls. There was no statistically significant difference between all groups, except for λ FLC concentrations between cases of PTLD and normal individuals (p = 0.016). The κ/λ sFLC ratios of cases and controls were within the renal range and normal range. Our results suggest that sFLC are not useful to predict PTLD development in renal transplant recipients.