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.

Relationship between M-Protein of Multiple Myeloma and False Positive Syphilis Serological Results / 中国实验血液学杂志

<p><b>BACKGROUND</b>The false positive in conventional syphilis serological test was found in patients with multiple myeloma (MM).</p><p><b>OBJECTIVE</b>To investigate the relationship between the M-protein of patients with MM and the false positive in conventional syphilis serologic test.</p><p><b>METHODS</b>The M-protein of 68 MM cases was typed with immunofixation electrophoresis and 68 cases of MM were screened with non-specific and specific syphilis serologic tests, then the samples with syphilic serological positive were chosen and confirmed with immonobloting test, finally the relationship between M protein of MM and the false positive of syphilis serological test were analysed.</p><p><b>RESULTS</b>Four out of 68 cases showed the positive in syphilis serological test and further were confimed to be false positive by immunoblotting test, the false positive rate was nearly 6%. The M-protein of MM patients in our hospital mostly possessed IgG, κ type, followed by IgA, κ type, light chain κ type. In general, κ : λ = 2.4 : 1. Among samples of 4 cases with syphilis serological positive 2 cases were of IgG and κ type, 1 case was of IgG, λ type, another 1 case was IgA, κ type.</p><p><b>CONCLUSION</b>The M-protein of IgG and IgA types in MM patients results in syphilis serological false positive reaction. The clinicians and laboratorial technicians should pay a great attention to screen the MM patients for the false positive syphilis serological test so as to avoid the misdiagnosis and subsequent embarassment.</p>

Role of Biology Based on Epigenetics in Multiple Myeloma / 中国实验血液学杂志

Multiple myeloma (MM) is a malignant tumor, characterized by dysplasia of clonal plasma cells in the bone marrow secreting large amounts of monoclonal immunoglobulin or fragments (M protein), resulting in damage in relevant organs or tissues. The biological complexity of MM is based on disrupted cancer pathways. Except the central role of cytogenetic abnormalities, epigenetic aberrations have also been shown to be involved in the occurrence and development of MM. Epigenetics of MM is mainly concentrated in the ways of DNA methylation, histone modifications and noncoding RNA, which have generated abnormal signaling pathways to regulate cell cycle and apoptosis of MM. In this article, advances of research on epigenetics of development, clinical diagnosis and treatments of MM are reviewed.

Expression of microRNA-221/222 in patients with monoclonal gammopathy of undetermined significance and multiple myeloma / 浙江大学学报·医学版

To detect the expression of miR-221/222 in serum and plasma cells in patients with monoclonal gammopathy of undetermined significance(MGUS) and multiple myeloma(MM), and to explore the possibility of miR-221/222 as biomarkers in the diagnosis and prognosis predicting of MGUS and MM.Bone marrow and serum samples from 14 patients with newly diagnosed MGUS, 81 patients with newly diagnosed or relapsed MM and 10 controls were collected from Sir Run Run Shaw Hospital of Zhejiang University and Tongde Hospital of Zhejiang Province during January 2013 and December 2015. The expressions of miR-221/222 in serum and in sorted CD138 positive plasma cells were detected by qRT-PCR, and the relative expression of miR-221/222 (Δct) was compared between the groups. Serum levels of miR-221 before and after treatment were compared in both remission group (=22) and refractory group (=13) in MM patients, and its correlation with serum level of β-MG was assessed using Pearson's correlation analysis.Serum levels of miR-221/222 in MGUS and MM groups were significantly higher than those in control group (all<0.01), while miR-221/222 levels in plasma cells were significantly lower in MGUS and MM groups than those in the control group (<0.05 or<0.01). No significant difference in miR-221/222 levels in serum and plasma cells was observed between MGUS group and MM group (all>0.05). There was no correlation between miR-221/222 levels in serum and plasma cells (=0.024 and -0.127, all>0.05), but miR-221 levels were correlated with miR-222 levels in both serum and plasma cells (=0.534 and 0.552, all<0.01). Receiver operating characteristic (ROC) curves showed that the areas under the curve (AUCs) of serum miR-221/222, plasma cell miR-221/222 in diagnosis of MGUS/MM were 0.968, 0.976, 0.801 and 0.727, respectively. There was no significant difference in serum level of miR-221 among MM patients with different paraprotein isotypes (>0.05), but serum level of miR-221 in patients with relapsed MM was higher than that in patients with newly diagnosed MM (<0.01). Compared with the patients with MGUS or MM stageⅠ and Ⅱ, patients with MM stage Ⅲ were of higher serum levels of miR-221 (<0.01). Serum level of miR-221 decreased after chemotherapy in the remission group (=51.5,<0.01), but such decrease was not observed in the refractory group (=67.5,>0.05). Serum level of β-MG was positively correlated with serum level of miR-221 (=0.524,<0.01).miR-221/222 in serum and plasma cells may be biomarkers for early diagnosis of MGUS, and are helpful for diagnosis and efficacy evaluation of MM.

Mieloma múltiple en el Hospital Carlos Andrade Marín, estado clínico al diagnóstico y sobrevida / Multiple myeloma in Carlos Andrade Marin Hospital, diagnostic and survival clinical status

Introducción: la mortalidad asociada a los pacientes con mieloma múltiple (MM) son los únicos datos disponibles en Ecuador. El presente estudio tiene por objetivo caracterizar la enfermedad, definir la tasa de mortalidad y describir los factores relacionados en los casos de MM tratados en el Hospital Carlos Andrade Marín. Materiales y métodos: análisis retrospectivo de datos demográficos, características clínicas de los pacientes con MM, recogidos de enero a diciembre de 2011. Resultados: 52 pacientes entre 29 a 89 años (media 61), 15 fueron mujeres (29%). 73% tenía un mieloma IgG, el 28% IgA y 19% fueron cadenas ligeras. Según el sistema de estadificación Durie y Salmon (D&S), 13% en etapa I, 25% en etapa II, 33% en estadío III. Fue excluido el 41% ya que la información no estaba disponible. Mortalidad en el estadío clínico avanzado del Mieloma (D&S etapa III) fue de 10%, en las etapas I y II no fueron registradas muertes. El daño renal fue más frecuente en la etapa III (33%) comparado con las etapas I (13%) y II (25%). Conclusiones: la mortalidad se asoció a un estadío avanzado del MM (etapa III) y al daño renal presente (29%).

Introduction: mortality associated with patients with multiple myeloma (MM) is the only data available in Ecuador. This study aims to characterize the disease, determine its mortality rate and describe related factors in the cases of MM treated at the Carlos Andrade Marin Hospital. Materials and methods: retrospective analysis of demographic data, clinical characteristics of patients with MM, collected between january and december 2011. Results: 52 patients between 29 to 89 years (mean 61), 15 were women (29%). 73% had an IgG myeloma, 28% IgA and 19% were light chains. According to the staging system Durie and Salmon (D & S) 13% in stage I, stage II 25%, 33% stage III. 41% was excluded because information was not available. Mortality in the advanced clinical stage of myeloma (D & S stage III) was 10% in stages I and II were not registering deaths. Renal damage was more frequent in stage III (33%) compared with stages I (13%) and II (25%). Conclusions: mortality was associated with advanced stages of MM (stage III) and kidney damage present (29%).

The characteristics of 62 cases of CD20-positive multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical and laboratory characteristics of mutiple myeloma patients with CD20 expression.</p><p><b>METHODS</b>Review the data of mutiple myeloma patients and analyze the clinical and laboratory characteristics of CD20 positive patients, compared with CD20 negative patients.</p><p><b>RESULTS</b>(1)Totally 465 cases of newly-diagnosed MM were collected with CD20 expression status detected by multi-color flow cytometry. Sixty two patients (13.3%) were CD20 positive and the others were negative. (2)No statistical differences were found between CD20 positive and negative groups about the sex ratio, age predominance, D-S staging, ISS staging, renal insufficiency rate, platelet count, LDH level and classifications by paraprotein(all P value>0.05). (3)Compared with those of CD20 negative patients, the hemoglobulin value(74.5 g/L vs 83.5 g/L, P=0.021), extramedullary involvement rate (3.5% vs 13.7%, P=0.029), CD56-positive rate(36.7% vs 68.8%,P=0.000), t(4;14)translocation rate(2.4% vs 24.0%, P=0.001) in CD20 positive patients were lower statistically. (4)Compared with those of CD20 negative patients, the percentage of plasma cells (0.400 vs 0.295, P=0.045) by marrow smear differential counting, the percentage of myeloma cells(20.0% vs 6.8%, P=0.000) by multi-color flow cytometry analysis, CD45-positive rate(12.1% vs 4.5%, P=0.018), CD79a-positive rate(9.8% vs 1.5%, P=0.013) and t(11;14) translocation rate(60.5% vs 14.4%, P=0.000)in CD20 positive patients were higher statistically. (5)There was no statistical differences about the overall response rate (ORR), complete response rate (CRR), TTP(time to progression), PFS(progression free survival) and overall survival (OS) between CD20 positive and negative groups.</p><p><b>CONCLUSION</b>CD20 positive rate is 13.3% in multiple myeloma pateints according to our data. CD20 poaitive myeloma were prone to residing in bone marrow and affecting erythropoiesis. Atypical immunophenotypes were more common, and the incidence of t(11;14) were increased markedly while that of t(4;14)were rare for CD20 positive multiple myeloma.</p>

Expression and significance of HSP90 in plasma of patients with multiple myeloma / 中国实验血液学杂志

This study was purposed to investigate the expression of heat shock protein 90 (HSP90) in peripheral blood plasma of patients with multipl myeloma (MM), and to explore its possible role in the pathogenesis of MM, and its relationship with treatment, prognosis and the outcome of patients. The peripheral blood samples from 58 patients with MM and 20 healthy volunteers were collected. The plasma concentration of HSP90 in patients and healthy volunteers was measured by ELISA. The results showed that the concentration of HSP90 in peripheral blood of patients with MM was significantly higher than that in the healthy volunteers [(32.398 ± 3.674) vs (25.762 ± 2.916) ng/ml] (P < 0.001). The concentration of HSP90 showed positively correlation with International Staging System(ISS) stage, therapeutic response, frequency of plasmocyte, globulin, immune globulin, M-protein, β2 micro-globulin, and light chain of MM patients (P < 0.05) ; while it showed little correlation with sex, age and type of MM patients (P > 0.05) . It is concluded that the HSP90 may be involved in the occurrence and development of MM. Detection of HSP90 in plasma would contribute to judge the clinical course, therapeutic efficacy and prognosis of MM patients.

Expression of serum GDF15 and its clinical significance in multiple myeloma patients / 中南大学学报(医学版)

OBJECTIVE@#To determine the serum level of the growth differentiation factor 15 (GDF15) in multiple myeloma (MM) patients and analyze its level with other clinical parameters, and to investigate its significance in the formation, development and prognosis assessment of MM.@*METHODS@#We used enzyme-linked immunosorbent assay (ELISA) to measure the serum level of GDF15 in an MM group (24 pre-treatment patients) and in 20 healthy controls. All patients' clinical data were collected.@*RESULTS@#The serum GDF15 level was significantly higher in the MM group [(1.37±0.64) ng/mL] than in the normal control group [(0.14±0.06) ng/mL, P0.05). After 3 cycles of chemotherapy, patients with a>50% reduction of M protein had a significant reduction of GDF15, while for the patients whose M protein did not decrease obviously, their corresponding serum GDF15 level increased.@*CONCLUSION@#The serum GDF15 level may reflect the tumor burden in the MM patients, which increases obviously, is related with ISS, positively correlated with serum M protein level, β2- microglobulin level, serum creatinine and negatively with hemoglobin concentration and platelet count. The change of serum GDF15 level has some relation with the extent of M protein reduction, suggesting it may be used as a marker for therapy response.

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

Clinical significance of abnormal protein bands in multiple myeloma treated with bortezomib-based induction regimen and autologous stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical significance of abnormal protein bands (APB) in multiple myeloma (MM) patients treated with bortezomib-based induction regimen and autologous stem cell transplantation (ASCT).</p><p><b>METHODS</b>Sixty-eight MM patients submitted to bortezomib-based induction therapy and ASCT from January 2007 to July 2012 were retrospectively studied. Monoclonal protein was detected by immunofixation electrophoresis (IFE).</p><p><b>RESULTS</b>Of all 68 patients, 33 (48.5%) patients had APB. At the first emergence of an APB, two patients with light chain type achieved CR and before transplantation, and thirty-one patients were after transplantation with median time of 104 (ranged 33-404) days. The median duration of APB appearance was 105 (ranged 35-801) days. Patients who developed APB compared with those without APB, had a significantly higher CR plus very good partial response (VGPR) rates (100.0% vs 85.7%%, P=0.017) and CR rates (87.9% vs 62.9%) (P=0.03). There were no significant differences in gender, age, HGB, ALB, β2-microglobulin, M protein type, Durie-Salmon and ISS stages, the case number of first line or second line treatment, induction courses of bortezomib-based regimen, and the mode of ASCT. With a median follow-up of 33.4 (ranged 7.0-71.7) months, patients with APB tended to have a longer overall survival (OS) versus non-APB patients, although no significant difference obtained (P＞0.05). Among APB patients, OS was longer in patients whose appearance of APB occurred ＜6 months after transplantation than those ≥ 6 months, but the significant difference was not obtained yet (P＞0.05).</p><p><b>CONCLUSIONS</b>Patients who developed APB had a significantly better response to bortezomib-based induction regimen followed ASCT. APB emergence has a good prognostic significance.</p>

Bcl-2 protein frequency in patients with high-risk diffuse large B-cell lymphoma / Frequência da proteína Bcl-2 em pacientes com linfoma difuso de grandes células B de alto risco

CONTEXT AND OBJECTIVE: Gene expression and immunohistochemical profiling of diffuse large B-cell lymphoma (DLBCL) have revealed important prognostic subgroups: germinal center B-cell-like (GCB-like) DLBCL and activated B cell-like (ABC-like) DLBCL. Although few reports on high-risk DLBCL are available, the prognosis for the GCB-like subgroup has been shown to be better than that of the ABC-like subgroup. The role of Bcl-2 as a predictor of survival in DLBCL cases is unclear and its expression varies between the two subgroups of DLBCL. In this study, we analyzed the frequency and prognostic impact of Bcl-2 protein expression in high-risk DLBCL cases. DESIGN AND SETTING: Retrospective cohort study among DLBCL patients treated at Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). METHODS: The prognostic impact of the expression of the proteins CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) and Bcl-2 on high-risk DLBCL cases was evaluated by means of immunohistochemistry. Seventy-three patients aged 18-60 years were evaluated for all these markers. RESULTS: Twenty-four cases (32.9 percent) were GCB-like and 49 (67.1 percent) were ABC-like, with no difference regarding complete remission, disease-free survival or overall survival rates. Twenty-seven patients (37 percent) showed Bcl-2 expression, which was the only independent factor predicting a worse prognosis for overall survival according to multivariate analysis. CONCLUSION: Bcl-2 protein was expressed in 37 percent of the high-risk DLBCL patients, without any difference between the ABC-like DLBCL and GCB-like DLBCL cases.

CONTEXTO E OBJETIVO: A expressão gênica e imunoistoquímica do linfoma difuso de grandes células B (LDGCB) vem permitindo a identificação de importantes subgrupos prognósticos: LDGCB do centro germinativo (CG) e LDGCB de células B ativadas (CBA). Entretanto, existem poucos dados disponíveis com LDGCB de alto risco, sendo o prognóstico dos LDGCB do CG melhor que os LDGCB de CBA. A participação do Bcl-2 como preditor de sobrevida nos LDGCB não é clara e sua expressão é variável entre os dois subgrupos de LDGCB. Neste estudo é avaliada a frequência e o prognóstico da expressão da proteína Bcl-2 em LDGCB de alto risco. TIPO DE ESTUDO E LOCAL: Estudo de coorte retrospectivo realizado entre portadores de LDGCB tratados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foi avaliado o impacto prognóstico da expressão das proteínas CD10, Bcl-6, MUM1 (multiple myeloma oncogene-1) e Bcl-2 por imunoistoquímica em LDGCB de alto risco. Foram avaliados, para todos os marcadores, 73 pacientes com idade de 18 a 60 anos. RESULTADOS: Vinte e quatro (32,9 por cento) pacientes foram classificados como LDGCB do CG e 49 (67,1 por cento) como LDGCB de CBA, sem diferença nas taxas de remissão completa, sobrevida livre de doença e sobrevida global. Vinte e sete (37 por cento) apresentaram expressão de Bcl-2, o qual foi o único fator preditivo independente de pior prognóstico de sobrevida global à análise multivariada. CONCLUSÃO: A expressão da proteína Bcl-2 ocorreu em 37 por cento dos portadores de LDGCB de alto risco, sem diferença entre os subgrupos de LDGCB do CG ou de CBA.

Establishment of a multiple myeloma local tumor model in mice / 中国实验血液学杂志

This study was purposed to establish a multiple myeloma local tumor model in the BLAB/c mice. Healthy BLAB/c mice were injected subcutaneously with 6 x 10(5) MPC-11 cells. In the peak time of the subcutaneous nodules observed, five mice were randomized selected to be executed and the subcutaneous nodules of these mice executed were used to detect the CD138 and kappa light chain by means of HE staining and the immunohistochemistry methods. The serum immunofixation electrophoresis (IFE) of tumor-bearing mice were performed at 5, 7, 9, 11, 12, 35 and 65 days after the initial MPC-11 cell injection. Hemoglobin level was assayed at 15 and 30 days after the initial MPC-11 cell injection. The serum levels of IL-6 were also assayed at 35 and 65 days after the initial MPC-11 cell injection. The tumor volume was monitored twice a week and their body weights were measured once a week. The results showed that the peak of the subcutaneous nodules appeared at 12 to 15 days after the initial MPC-11 cell injection. The serum monoclonal immunoglobulin could be detected at 12 days after MPC-11 cell injection. The results of HE staining and immuno-histochemistry assay for detection of CD138 and kappa light chain positive expressions proved that the subcutaneous tumor nodules originated from MPC-11 plasmacytes. The serum monoclonal protein (M protein) of the tumor-bearing mice was detected at 12 days after bearing tumor which manifested thick bands of IgG and kappa light chain. The peak time of mortality was at 20 to 40 days after the initial MPC-11 cell injection, and the median survival time was 31 days. Anemia in mice appeared at 15 days. There was a significant difference of Hb level between the tumor-bearing group and the normal group at 15 and 30 days respectively (p < 0.05). The serum level of IL-6 in tumor-bearing mice was higher than that in the normal group. It is concluded that to establish the multiple myeloma local tumor model in mice by using subcutaneous injection of MPC-11 cells has various advantages, such as simple method of model established, relative high success of bearing tumor, easy observation of tumor growth change and so on. This model can be useful for studying and evaluating the therapeutic efficacy for multiple myeloma through monitoring the changes of tumor size, serum IL-6 level and serum immunofixation electrophoresis.

Establishment of a bortezomib-resistant myeloma cell line and differential proteins analysis by MALDI-OF-MS / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To establish a bortezomib-resistant myeloma cell line and to investigate its mechanism.</p><p><b>METHODS</b>Bortezomib-resistant NCI-H929 cell line (NCI-H929B) was obtained by stepwise increasing extracellular concentrations of bortezomib over a period of 8 months. The biological characteristics of NCI-H929 and NCI-H929B were observed. Proteins from NCI-H929B cell and NCI-H929 cell were extracted, run on two-dimensional gel electrophoresis. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) and mass spectrometry (MS) were used to identify proteins. Western blot was used to further verify differential proteins.</p><p><b>RESULT</b>Bortezomib-resistant cell line NCI-H929B was established. NCI-H929B exhibits a 23.5-fold level of resistance to bortezomib as compared to the parental cell line NCI-H929. There were no significant differences in cellular biology of cell growth curve and cell cycle distribution between NCI-H929 and NCI-H929B cell lines.Whole proteins of NCI-H929 and NCI-H929B myeloma cell lines were extracted by two-dimensional gel electrophoresis. Gel-image analysis revealed that there were 17 differential protein spots. A total of 14 differential protein spots were successfully identified by MALDI-TOF-MS. The result of Western blot was consistent with 2-DE.</p><p><b>CONCLUSION</b>A bortezomib-resistant human myeloma cell line NCI-H929B was successfully established. The differentially expression of proteomes may be useful for study of the bortezomib-resistant mechanisms and the molecular markers of MM.</p>

Non-secretory myeloma: a rare variant of multiple myeloma

The spectrum of plasma cell neoplasm represents indolent conditions like Monoclonal Gammopathy of Undetermined Significance [MGUS] to more aggressive multiple myeloma and plasma cell leukemia. Non-secretory myeloma comprises less than 01% of this spectrum where serum protein electrophoresis and quantitative immunoglobulins remain essentially normal. We are presenting a case report of this rare variant involving the sternum of an adult male

Production and characterization of murine monoclonal antibodies recognizing conformational and linear epitopes localized on human IgA2 molecules

There are two subclasses of human IgA [IgA1 and IgA2] that differ in antigenic properties and in chemical composition. The constant domains of alpha1 and alpha2 heavy chains have >95% sequence homology though major structural differences exist in the hinge region. Quantitation of IgA subclass levels depends on the availability of monoclonal antibodies [MAbs] specific for conserved conformational or linear epitopes restricted to each subclass. To produce, select and characterize monoclonal antibodies specific for human IgA2. Splenocytes from BALB/C mice immunized with a human IgA2 myeloma protein were fused with SP2/0 myeloma cells. Fused cells were grown in hypoxanthine, aminopterine and thymidine [HAT] selective medium and cloned by limiting dilution assay. Antibody [Ab] secreting cells were screened by enzyme-linked immunosorbent assay [ELISA] and the specificity of secreted MAbs was further analyzed, using a panel of purified myeloma proteins and some animal sera by ELISA and immunoblotting. The affinity constant [K[aff]] was also determined by ELISA. Four murine hybridoma clones designated 2F20G5, 2F20B5, 3F20E3 and 6F20H11 were obtained that secreted MAbs specific for the human IgA2. 2F20G5 and 6F20H11 MAbs react with linear epitope[s] while 2F20B5 and 3F20E3 react with conformational epitope[s] located to human IgA2 subclass. 2F20G5 MAb displays a weak cross-reactivity with monkey and rabbit sera and a strong cross-reactivity with cat and dog sera while the other three MAbs showed no cross-reactivity with the animal sera tested. These MAbs, especially 6F20H11 with high affinity constant [6.03 x10[9] M[-1]] are useful tools for quantitation of human IgA2 subclass levels in various diseases. Cross-reactivity of 2F20G5 MAb with some animal sera suggests phylogenic conservation of the epitope recognized by this MAb

Economical choices in setting up a diagnostic myeloma laboratory.

In setting up a diagnostic myeloma laboratory the popular, highly automated and otherwise excellent choices of equipment and laboratory practices, so exorbitantly raise costs that the sustainability, even in large government hospitals in third world countries may become difficult. Based on our experience in a regional cancer center in India, we offer here, guidelines for carrying out high resolution electrophoresis, densitometry, immunofixation and urine concentration. We show that by simply employing well established techniques and doing them properly, one can get results of excellent quality at minimum cost and minimum dependence on costly imports.

A Case of Multiple Myeloma with Biclonal (IgG-K and IgA-K) M-proteins / 대한임상병리학회지

Two M-protein peaks in serum protein electrophoresis are rarely present in patients with plasma cell discrasia. We describe a 72-year-old male patient with multiple myeloma secreting biclonal M-proteins, which were confirmed by immunofixation. Immunoelectrophoresis has some difficulties to dectect M components when a very small amount of M-protein develops an equivocally abnormal precipitation arc. In this case, serum protein electrophoresis revealed two M peaks, one in beta and the other in gamma globulin region. An immunoelectrophoresis revealed unequivocally abnormal precipitation arcs in IgA and K light chain regions, but the arc in IgG region was equivocal. We performed an immunofixation and confirmed biclonal gammopathy, IgA-K and IgG-K types. This result supports the view that immunofixation is an useful confirmatory test when immunoelectrophoresis results are equivocal.

Multiple myeloma complicated by Kaposi sarcoma

A fifty-one-year old female patient presented to Karama Teaching Hospital in May, 1986 with clinical picture of congestive heart failure due to severe anemia. She had some atypical features of multiple myeloma with genemlised lymphadenopathy. Her Investigations confirmed the presence of multiple myeloma complicated by Kaposi sarcoma. Three months after discharge from hospital, the patient died at home