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Monoclonal Gammopathy (monoclonal + gammopathy)
Selected AbstractsMYELIN PROTEIN P-0-SPECIFIC IGM PRODUCING MONOCLONAL B CELL LINES WERE ESTABLISHED FROM POLYNEUROPATHY PATIENTS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS)JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2002M Kvarnstrom Monoclonal expansion of B cells and plasma cells, producing antibodies against ,self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenstroms'macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P-0, using beads coated with P-0. P-0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein-Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P-0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5(+) positive, although the expression declined in vitro over time. The anti-P-0 antibodies were of IgM-lambda type. The antibodies belonged to the V(H)3 gene family with presence of somatic mutations. The IgM reacted with P-0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5(+) clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P-0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation. [source] PAINFUL NEUROPATHY, MONOCLONAL GAMMOPATHY AND AMYLOID DEPOSITS: RESPONSE TO THERAPY IN 3 CASESJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002Article first published online: 11 MAR 200 Siciliano G.1, D'Avino C.1, Panichi V.2, Azzarà A.3, Del Corona A.1, Pollina L.3, Murri L.1 1Department of Neuroscience, 2Department of Internal Medicine and 3Department of Oncology,University of Pisa-Italy Amyloidosis is a systemic disease with a wide organic involvement. Amyloidotic polyneuropathies may be genetic in their origin or present in association with a number of chronic inflammatory dysimmune disorders. We report on three patients affected by predominantly sensitive polyneuropathy, monoclonal gammopathy and amyloidosis. Patient 1. Woman, 72 years old, with a one year history of painful paraesthesias, ataxic gait and demyelinating predominantly sensitive polyneuropathy at 4 limbs also with involvement of sympathetic fibres. Blood protein electrophoresis showed a monoclonal gammopahty (IgG-k) with normal bone marrow biopsy and positivity for amyloid at fat biopsy. The patient has been treated with melphalan 0.2 mg/Kg/day+prednisone 100 mg/day for 7 days each month for 6 months with good efficacy and only a transient reduction in platelet and white blood cells count. Patient 2. Man, 60 years old, new diagnosis of diabetes with a 9 month history of painful paraesthesias and hyposthenia, a demyelinating sensory-motor polyneuropathy at 4 limbs. The patient presented an IgG-, monoclonal gammopathy with normal bone marrow biopsy, fat biopsy but not sural nerve biopsy positive for amyloid. The patient underwent melphalan+prednisone therapy, with insulinic control of glycemia. He presented a clear-cut improvement in sensitive-motor symptomatology. Patient 3. Man, 72 years old, with a 15 year history of ulcerous rectocolites. Since 1998 started complaining of paraesthesias and disaesthesias at four limbs associated with gait disturbances. The patient presented an IgG-, monoclonal gammopathy with normal bone marrow aspiration and elevated serum Interleukin-6 levels, fat biopsy positive for amyloid, and high anti-MAG antibodies titer (1:100000). Because of RCU, melphalan therapy was excluded and the patient is at the moment under fludarabine (25 mg/m2/day) ev for 5 days each 6 weeks for 6 bouts. [source] Primary Hyperparathyroidism and Monoclonal Gammopathy in a DogJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2009G. Benchekroun First page of article [source] Multiple myeloma: A review of the epidemiologic literatureINTERNATIONAL JOURNAL OF CANCER, Issue S12 2007Dominik D. Alexander Abstract Multiple myeloma, a neoplasm of plasma cells, accounts for ,,15% of lymphatohematopoietic cancers (LHC) and 2% of all cancers in the US. Incidence rates increase with age, particularly after age 40, and are higher in men, particularly African American men. The etiology is unknown with no established lifestyle, occupational or environmental risk factors. Although several factors have been implicated as potentially etiologic, findings are inconsistent. We reviewed epidemiologic studies that evaluated lifestyle, dietary, occupational and environmental factors; immune function, family history and genetic factors; and the hypothesized precursor, monoclonal gammopathies of undetermined significance (MGUS). Because multiple myeloma is an uncommon disease, etiologic assessments can be difficult because of small numbers of cases in occupational cohort studies, and few subjects reporting exposure to specific agents in case,control studies. Elevated risks have been reported consistently among persons with a positive family history of LHC. A few studies have reported a relationship between obesity and multiple myeloma, and this may be a promising area of research. Factors underlying higher incidence rates of multiple myeloma in African Americans are not understood. The progression from MGUS to multiple myeloma has been reported in several studies; however, there are no established risk factors for MGUS. To improve our understanding of the causes of multiple myeloma, future research efforts should seek the causes of MGUS. More research is also needed on the genetic factors of multiple myeloma, given the strong familial clustering of the disease. © 2007 Wiley-Liss, Inc. [source] The histological and pathogenetic spectrum of cutaneous disease in monoclonal gammopathiesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2008Franco Rongioletti The dermatological disorders associated with monoclonal gammopathies are clinically heterogeneous and may be divided into four groups with distinctive pathogenetic mechanisms (a) specific (infiltrative) disorders including primary and secondary cutaneous plasmacytoma and cutaneous lymphoplasmacytic infiltration of Waldenström's disease (b) skin disorders because of the deposition of monoclonal immunoglobulin (M protein), including amyloidoisis macroglobulinemia cutis, light chain deposition of Randall's disease, follicular spicules of the nose, and cryoglobulinemia (c) skin disorders associated with monoclonal gammopathies, including highly associated (>50%), weakly associated (<50%) or anecdotal and (d) miscellaneous (non specific). In most cases, histopathology is crucial to confirm or to diagnose those skin conditions and is also very useful to understand their pathogenetic mechanisms. [source] MYELIN PROTEIN P-0-SPECIFIC IGM PRODUCING MONOCLONAL B CELL LINES WERE ESTABLISHED FROM POLYNEUROPATHY PATIENTS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS)JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2002M Kvarnstrom Monoclonal expansion of B cells and plasma cells, producing antibodies against ,self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenstroms'macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P-0, using beads coated with P-0. P-0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein-Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P-0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5(+) positive, although the expression declined in vitro over time. The anti-P-0 antibodies were of IgM-lambda type. The antibodies belonged to the V(H)3 gene family with presence of somatic mutations. The IgM reacted with P-0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5(+) clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P-0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation. [source] Occurrence of dysregulated oncogenes in primary plasma cells representing consecutive stages of myeloma pathogenesis: indications for different disease entitiesBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2003Thomas Rasmussen Summary. This study investigated the expression pattern in primary plasma cells (PCs) of putative oncogenes suggested to be involved in multiple myeloma (MM) development. cDNA archives were generated by global reverse transcription polymerase chain reaction from CD38++/CD19,/CD56,/++ aberrant PCs of a prospective cohort of 96 subjects, including healthy individuals, patients with monoclonal gammopathies of undetermined significance (MGUS), MM and MM with extramedullary manifestations (ExMM). The cDNA archives were analysed quantitatively for expression of the cyclin D1, fibroblast growth factor receptor 3 (FGFR3), C-MYC, C-MAF and cyclin D3 oncogenes. In addition, all patients were screened for IGH,MMSET hybrid transcripts. None of the analysed oncogenes was randomly distributed. C-MYC and cyclin D3 expression increased at the extramedullary transformation stage. Furthermore, C-MYC and cyclin D3 expression in CD56+ MM was similar to MGUS, whereas CD56, MM was similar to ExMM. FGFR3/IGH,MMSET was only observed among CD56+ MM patients, whereas an increased frequency of C-MAF dysregulation was seen among CD56, MM. High cyclin D1 expression levels were identified at similar frequencies at all stages, whereas the frequency of patients with low cyclin D1 levels increased during MM development. These data support the stepwise transformation model accumulating genetic alterations and proliferative capacity during MM initiation and development resulting in different clinical entities. [source] Characterization of bone marrow T cells in monoclonal gammopathy of undetermined significance, multiple myeloma, and plasma cell leukemia demonstrates increased infiltration by cytotoxic/Th1 T cells demonstrating a squed TCR-V, repertoireCANCER, Issue 6 2006Martin Pérez-Andres M.D. Abstract BACKGROUND The majority of studies published to date regarding the role of the bone marrow (BM) microenvironment in the pathogenesis of monoclonal gammopathies (MG) have focused on the interaction between stroma cells and plasma cells, whereas information concerning the lymphocytes infiltrating the tumor microenvironment is scanty. METHODS The authors measured the distribution, TCR-V, repertoire, immunophenotype, and functional characteristics of different subsets of BM T lymphocytes from 61 nontreated patients with MG (30 patients with MG of undetermined significance [MGUS], 27 patients with multiple myeloma [MM], and 4 patients with plasma cell leukemia [PCL]). RESULTS The authors found a significantly increased rate of BM infiltration by T cells in all patient groups, at the expense of CD4+CD8, and CD4,CD8, T lymphocytes and both CD4+CD28, and CD8+CD28, cytotoxic/effector T cell subsets, and associated with TCR-V, expansions in both CD4+ and CD8+ BM T cells in the majority of patients with MGUS, MM, and PCL. Moreover, the percentage of T cells secreting interferon (IFN)-, was found to be increased (P , 0.05) both in CD4+ and CD8+ T cells in MGUS and MM patients, and a higher plasma concentration of IFN-, was found in patients with MM. It is interesting to note that a positive correlation was noted between the proportion of CD28, and both the percentage of IFN-,,secreting cells and the proportion of expanded TCR-V, lymphocytes within the total BM CD4+ T cells. CONCLUSIONS The results of the current study demonstrated an increased infiltration of BM by T cells associated with frequent TCR-V, expansions and a more prominent cytotoxic/Th1 phenotype in all the patient groups studied. Cancer 2006. © 2006 American Cancer Society. [source] Multiparameter immunophenotyping by flow cytometry in multiple myeloma: The diagnostic utility of defining ranges of normal antigenic expression in comparison to histology,CYTOMETRY, Issue 4 2010Elisa Cannizzo Abstract Background: Numerous studies have reported on the immunophenotype of plasma cells (PCs) in monoclonal gammopathy of undetermined significance (MGUS) and in plasma cell myeloma (PCM), but very few have examined the immunophenotype of normal PCs. In this study, an objective definition of normal range of expression for each antigen was found on normal control PCs. Using these new ranges of normal expression (new method) is different from using a static 20% of PCs cut-off for all antigens as described in the literature (traditional method). These newly calculated normal ranges for each antigen were applied to our data, and compared to histologic and immunohistochemical findings. Methods: Bone marrow samples from 46 patients with PC neoplasms and 15 normal controls were studied. A minimum of 100 PC were analyzed for each patient and control sample. An 8-color staining method was applied to study the immunophenotype of PCs, using a BD FACSCanto II. Results: By the new ranges of normality calculated in this study it was determined that different antigens have different level of expression on polyclonal PCs. CD19 correlated with histology by both the traditional and new methods, but had superior correlation by the new method. Conclusions: This report is the first 8-color immunophenotypic study of PCM in which a "range of normal expression" for each antigen is defined. This is a critical step to help distinguish between a normal and neoplastic PC immunophenotype and discern which antigens are of diagnostic importance. © 2010 Clinical Cytometry Society [source] Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytologyCYTOPATHOLOGY, Issue 3 2010U. Handa U. Handa, S. Chhabra and H. Mohan Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology Objective:, Plasma cell tumours represent autonomous proliferation of plasma cells and can manifest as multiple myeloma, monoclonal gammopathy of undetermined significance, variants of plasma cell myeloma or plasmacytoma. Methods:, We report 12 cases of plasma cell tumours, which were initially diagnosed as plasmacytoma on fine needle aspiration cytology (FNAC). The patients were further subjected to bone marrow examination, serum electrophoresis, urine examination for Bence,Jones proteins, and x-ray examination of the skeleton. Results:, The cytological smears from all cases were cellular and showed numerous plasma cells in varying degrees of maturity. Subsequent to investigations, five cases were labelled as multiple myeloma with secondary extramedullary plasmacytoma, three as solitary bone plasmacytoma and two as primary extramedullary plasmacytoma. In the remaining two cases, bone marrow and urine examination findings were not available, so a conclusive diagnosis of multiple myeloma or solitary plasmacytoma could not be made. Conclusion:, The study highlights the role of FNAC in the diagnosis of plasma cell tumours. Subsequent work-up and follow-up of these patients is important to rule out the presence of multiple myeloma. [source] Update on therapeutic options in Waldenström macroglobulinemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Xavier Leleu Abstract Waldenström macroglobulinemia (WM) is a B-cell disorder characterized primarily by bone marrow infiltration with lymphoplasmacytic cells (LPCs), along with demonstration of an IgM monoclonal gammopathy in the blood. WM remains incurable, with 5,6 yr median overall survival for patients with symptomatic WM. The main therapeutic options include alkylating agents, nucleoside analogues, and rituximab, either in monotherapy or in combination. Studies involving combination chemotherapy are ongoing, and preliminary results are encouraging. However, there are several limitations to these approaches. The complete response rate is low and the treatment free survival are short in many patients, no specific agent or regimen has been shown to be superior to another, and no treatment has been specifically approved for WM. As such, novel therapeutic agents are needed for the treatment of WM. In ongoing efforts, we and others have sought to exploit advances made in the understanding of the biology of WM so as to develop new targeted therapeutics for this malignancy. These efforts have led to the development of proteasome inhibitors, of them bortezomib, several Akt/mTor inhibitors, such as perifosine and Rad001, and immunomodulatory agents such as thalidomide and lenalidomide. Many agents and monoclonal antibodies are currently being tested in clinical trials and seem promising. This report provides an update of the current preclinical studies and clinical efforts for the development of novel agents in the treatment of WM. [source] Management of acquired von Willebrand's sryndrome in a patient requiring major surgeryHAEMOPHILIA, Issue 6 2005J. M. Maddox Summary., We present the case of a patient with acquired von Willebrand's syndrome and a monoclonal gammopathy of undetermined significance who required cystectomy for relapsed transitional cell carcinoma (TCC) of the bladder. We demonstrated that infused von Willebrand factor (VWF) containing factor VIII concentrates had an unacceptably short half-life, but that this was significantly prolonged following combined therapy with plasma exchange and intravenous immunoglobulin (IVIgG). This approach was successfully utilized peri-operatively, with the total surgical blood loss less than would be expected even for a haemostatically normal patient. Trough VWF antigen and Ristocetin co-factor activity levels fell on the second postoperative day and we therefore administered further IVIgG. Levels again fell on the fifth postoperative day with the development of a Staphylococcus aureus septicaemia. At this point bleeding occurred from a surgical drain site requiring ,factor VIII inhibitor bypass activity' to secure haemostasis while further plasma exchange and IVIgG were administered. Now 5 years later, there is no evidence of recurrence of the TCC or progression of the monoclonal gammopathy. [source] Identification of antigenic targets of paraproteins by expression cloning does not support a causal role of chronic antigenic stimulation in the pathogenesis of multiple myeloma and MGUSINTERNATIONAL JOURNAL OF CANCER, Issue 2 2007Klaus-Dieter Preuss Abstract Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins have been suggested to play an important role as growth stimulators in the pathogenesis of these neoplasms. To identify such targets, we screened cDNA libraries from human testis, lung and breast cancer, bovine and porcine muscle and wheat germ for reactivity with paraproteins in the sera from 115 patients with MGUS and MM. Of >6 × 108 paraprotein,antigen interactions screened, an IgA paraprotein from a female patient bound to sperm-specific cylicin-2, and 3 IgG paraproteins bound to tripeptidyl-peptidase-II (TPP-2), insulin-like growth-factor binding-protein-2 (IGFBP-2) and porcine kinesin. Specificity was confirmed by reverse Western blots using recombinant antigens. The broad spectrum of auto-, allo- and heteroantigens as targets of human paraproteins in patients without signs of chronic antigenic stimulation renders a causal role of the antigenic stimulus in the pathogenesis of MGUS and MM unlikely. © 2007 Wiley-Liss, Inc. [source] Schnitzler syndrome: response to anakinra in two cases and a review of the literatureINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2009Christian Schuster MD Background, Schnitzler syndrome is a rare disease characterized by a chronic urticarial eruption and monoclonal gammopathy, as well as clinical and laboratory signs of inflammation. The pathophysiology is still unknown, although various autoantibody-mediated mechanisms have been described. Complete remission of symptoms has been reported recently in patients with Schnitzler syndrome treated with anakinra, an interleukin-1 receptor antagonist. Methods, Two patients with Schnitzler syndrome treated with anakinra therapy are presented. Results, We report two cases of nearly complete remission of symptoms in Schnitzler syndrome after the initiation of anakinra therapy, and the first observation of a relapse under continuous daily anakinra therapy. A review of the published literature on the treatment of Schnitzler syndrome with anakinra is presented. Conclusions, Based on published data, monotherapy with anakinra is currently the most promising treatment for Schnitzler syndrome, because it is able to induce complete remission of symptoms. [source] Eosinophilic fasciitis: demographics, disease pattern and response to treatment: report of 12 cases and review of the literatureINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2008Lindsay Bischoff Senior Medical Student Background, Eosinophilic fasciitis is a rare scleroderma-like illness. The clinical spectrum of the disease has evolved since its initial description. Methods, We identified all patients diagnosed with eosinophilic fasciitis over the past 10 years at our scleroderma clinic. Demographics, disease pattern, serologies, tissue pathology and reponse to treatment were all recorded. Results, Twelve patients with eosinophilic fasciitis were identified in our clinic over the past 10 years. The mean age at diagnosis was 49.8 ± 9.8 years, with nine female and three male patients. The first symptoms were noticed at an average of 8.8 ± 6.1 months before diagnosis. The mean initial absolute peripheral blood eosinophil count was 1188 ± 1059 cells/L. Two patients had a monoclonal gammopathy, and two had positive ANA titers. All patients received corticosteroids, 10 of whom received the equivalent dose of > 20 mg/day of prednisone for more than a month. Five patients received hydroxychloroquine, two received methotrexate, one received cyclosporine, one received topical tacrolimus, and one received sulfasalazine. At a mean follow up of 17.6 months (range 2,94 months), 8 patients had a good response to treatment, 2 patients had no effect, and 2 patients had a poor response to treatment. Conclusion, High dose corticosteroid treatment lasting longer than a month with or without an immunosuppressive agent helped most patients with eosinophilic fasciitis, best results seen in those patients who were initiated treatment early on after their first symptoms. [source] The Schnitzler syndrome: Chronic urticaria and monoclonal gammopathy , an autoinflammatory syndrome?JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 8 2008Elisabeth Eiling Summary Schnitzler syndrome describes the simultaneous occurrence of monoclonal gammopathy and chronic urticaria with at least two additional minor symptoms (arthralgia, bone pain, fever of uncertain origin, hepato- or splenomegaly, lymphadenopathy, increased erythrocyte sedimentation rate, leukocytosis/thrombocytosis or increased bone density). Schnitzler syndrome is not wellknown and very likely under-recognized. Comprehensive diagnostic examinations are necessary to rule out other diseases, especially those of hematologic origin. Close interdisciplinary collaboration is mandatory. The etiology of Schnitzler syndrome is unclear, but the rapid response to the interleukin-1 receptor inhibitor anakinra underlines the pivotal role which the proinflammatory cytokine interleukin-1 may play in the pathophysiology of this potentially autoinflammatory disorder. [source] Necrobiotic xanthogranuloma with paraproteinemia; an atypical caseJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 1 2008Yoshiyuki Ito Summary Necrobiotic xanthogranuloma (NXG) is a rare marker for paraproteinemia. An 86-year-old woman had a one year history of large red-yellow to brown annular plaques involving all limbs. Biopsies showed a non-palisading granuloma with numerous multinucleated giant cells showing prominent elastophagocytosis and extensive areas of necrobiosis throughout the entire dermis. Complete loss of elastic fibers was observed in the central atrophic area of an annular plaque. Small vascular thromboses were also present. Laboratory findings revealed paraproteinemia of IgG-lambda type. Immunohistochemical staining detected the presence of roughly equal numbers of IgG-lambda-and IgG-kappa-staining plasma cells in the dermis. We diagnosed NXG with paraproteinemia with monoclonal gammopathy (IgG-lambda type) of unknown significance. [source] Light-chain-restricted plasmacellular infiltrates in necrobiosis lipoidica , a clue to an underlying monoclonal gammopathyJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2005Adina M. Cioc Background:, Necrobiosis lipoidica (NL) is a member of the palisading granulomatous dermatitides that is associated, in most cases, with diabetes mellitus. However, there are an increasing number of cases of NL associated with other forms of systemic disease. We describe a novel case of NL associated with a light-chain-restricted plasmacellular infiltrate; subsequent investigations established an underlying monoclonal gammopathy. Methods:, Skin biopsy material was obtained and was processed in the usual fashion for hematoxylin and eosin (H&E) examination. Immunohistochemical staining was performed by utilizing kappa and lambda monoclonal antibodies (Dako Corporation, Carpentiera, CA, USA). Kappa and lambda in situ hybridization was also performed (Ventana Medical Systems, Tucson, AZ, USA). Results:, A 55-year-old woman with a 5-year history of bilateral thigh subcutaneous nodules underwent a skin biopsy, showing typical changes of NL; there was a concomitant prominent perivascular plasmacellular infiltrate. Kappa light chain restriction was observed amid the plasmacellular infiltrate. Bone marrow biopsy and immunophenotyping studies revealed a clonal plasmacytosis with kappa light chain restriction. Conclusions:, Granulomatous inflammation, including NL, may be a cutaneous paraneoplastic expression of low-grade B-cell lymphoproliferative disease in the context of an underlying plasma cell dyscrasia. [source] Chronic hepatitis C associated with monoclonal gammopathy of undetermined significanceJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2003KEI HAMAZAKI Abstract Background: Two patients were admitted to Mie Prefectural General Medical Center and diagnosed as chronic hepatitis C complicated with monoclonal gammopathy of undetermined significance (MGUS). Methods: The MGUS class were immunoglobulin (Ig)G. The hepatitis C virus (HCV) RNA genotype was Ib. Based on these findings, they were diagnosed as chronic hepatitis C complicated with MGUS. Results: Histological studies showed chronic hepatitis in the liver and a mild rise in plasma cells without dysplasia and abnormalities in the bone marrow. Serum examination for cryoglobulin was negative. Conclusion: Chronic HCV infection might play a pathogenic role in the multistage process leading to lymphoproliferative disorders. © 2003 Blackwell Publishing Asia Pty Ltd [source] A case of POEMS syndrome with high concentrations of interleukin-6 in pericardial fluidJOURNAL OF INTERNAL MEDICINE, Issue 2 2001N. Shikama Abstract. Shikama N, Isono A, Otsuka Y, Terano T, Hirai A (Department of Internal Medicine, Chiba Municipal Hospital; and Second Department of Internal Medicine, Chiba University School of Medicine, Chiba, Japan). A case of POEMS syndrome with high concentrations of interleukin-6 in pericardial fluid. J Intern Med 2001; 250: 170,173. The POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy of various forms, monoclonal gammopathy, skin changes) is a rare multisystem disorder of unknown pathogenesis. Overexpression of proinflammatory cytokines has been implicated in the pathogenesis of POEMS syndrome, however, it is not known whether there is an association between abnormalities in cytokines and pericardial fluid. We present a case of POEMS syndrome with high concentrations of interleukin-6 (IL-6) in pericardial fluid. In our patient, pericarditis developed into cardiac tamponade, and the concentration of IL-6 in pericardial fluid was remarkably elevated compared with that in serum (1760 vs. 6.57 pg mL,1). We suggest that IL-6 is associated with the progression or maintenance of pericarditis as a result of POEMS syndrome. [source] Improving fatigue assessment in immune-mediated neuropathies: the modified Rasch-built fatigue severity scaleJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2009Sonja I. Van Nes Abstract Fatigue is a major disabling complaint in patients with immune-mediated neuropathies (IN). The 9-item fatigue severity scale (FSS) has been used to assess fatigue in these conditions, despite having limitations due to its classic ordinal construct. The aim was to improve fatigue assessment in IN through evaluation of the FSS using a modern clinimetric approach [Rasch unidimensional measurement model (RUMM2020)]. Included were 192 stable patients with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or polyneuropathy associated with monoclonal gammopathy of undetermined significance (MGUSP). The obtained FSS data were exposed to RUMM2020 model to investigate whether this scale would meet its expectations. Also, reliability and validity studies were performed. The original FSS did not meet the Rasch model expectations, primarily based on two misfitting items, one of these also showing bias towards the factor ,walking independent.' After removing these two items and collapsing the original 7-point Likert options to 4-point response categories for the remaining items, we succeeded in constructing a 7-item Rasch-built scale that fulfilled all requirements of unidimensionality, linearity, and rating scale model. Good reliability and validity were also obtained for the modified FSS scale. In conclusion, a 7-item linearly weighted Rasch-built modified FSS is presented for more proper assessment of fatigue in future studies in patients with immune-mediated neuropathies. [source] MYELIN PROTEIN P-0-SPECIFIC IGM PRODUCING MONOCLONAL B CELL LINES WERE ESTABLISHED FROM POLYNEUROPATHY PATIENTS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS)JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2002M Kvarnstrom Monoclonal expansion of B cells and plasma cells, producing antibodies against ,self' molecules, can be found not only in different autoimmune diseases, such as peripheral neuropathy (PN), but also in malignancies, such as Waldenstroms'macroglobulinaemia and B-type of chronic lymphocytic leukaemia (B-CLL), as well as in precancerous conditions including monoclonal gammopathy of undetermined significance (MGUS). About 50% of patients with PN-MGUS have serum antibodies against peripheral nerve myelin, but the specific role of these antibodies remains uncertain. The aims of the study were to establish, and characterize, myelin-specific B cell clones from peripheral blood of patients with PN-MGUS, by selection of cells bearing specific membrane Ig-receptors for myelin protein P-0, using beads coated with P-0. P-0-coated magnetic beads were used for selection of cells, which subsequently were transformed by Epstein-Barr virus. The specificity of secreted antibodies was tested by ELISA. Two of the clones producing anti-P-0 antibodies were selected and expanded. The magnetic selection procedure was repeated and new clones established. The cells were CD5(+) positive, although the expression declined in vitro over time. The anti-P-0 antibodies were of IgM-lambda type. The antibodies belonged to the V(H)3 gene family with presence of somatic mutations. The IgM reacted with P-0 and myelin-associated glycoprotein (MAG), and showed no evidence for polyreactivity, in contrast to other IgM CD5(+) clones included in the study as controls. The expanded clones expressed CD80 and HLA-DR, which is compatible with properties of antigen-presenting cells. The immunomagnetic selection technique was successfully used for isolation of antimyelin protein P-0-specific clones. The cell lines may provide useful tools in studies of monoclonal gammopathies, leukaemia, and autoimmune diseases, including aspects of antigen-presentation by these cells followed by T cell activation. [source] PAINFUL NEUROPATHY, MONOCLONAL GAMMOPATHY AND AMYLOID DEPOSITS: RESPONSE TO THERAPY IN 3 CASESJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2002Article first published online: 11 MAR 200 Siciliano G.1, D'Avino C.1, Panichi V.2, Azzarà A.3, Del Corona A.1, Pollina L.3, Murri L.1 1Department of Neuroscience, 2Department of Internal Medicine and 3Department of Oncology,University of Pisa-Italy Amyloidosis is a systemic disease with a wide organic involvement. Amyloidotic polyneuropathies may be genetic in their origin or present in association with a number of chronic inflammatory dysimmune disorders. We report on three patients affected by predominantly sensitive polyneuropathy, monoclonal gammopathy and amyloidosis. Patient 1. Woman, 72 years old, with a one year history of painful paraesthesias, ataxic gait and demyelinating predominantly sensitive polyneuropathy at 4 limbs also with involvement of sympathetic fibres. Blood protein electrophoresis showed a monoclonal gammopahty (IgG-k) with normal bone marrow biopsy and positivity for amyloid at fat biopsy. The patient has been treated with melphalan 0.2 mg/Kg/day+prednisone 100 mg/day for 7 days each month for 6 months with good efficacy and only a transient reduction in platelet and white blood cells count. Patient 2. Man, 60 years old, new diagnosis of diabetes with a 9 month history of painful paraesthesias and hyposthenia, a demyelinating sensory-motor polyneuropathy at 4 limbs. The patient presented an IgG-, monoclonal gammopathy with normal bone marrow biopsy, fat biopsy but not sural nerve biopsy positive for amyloid. The patient underwent melphalan+prednisone therapy, with insulinic control of glycemia. He presented a clear-cut improvement in sensitive-motor symptomatology. Patient 3. Man, 72 years old, with a 15 year history of ulcerous rectocolites. Since 1998 started complaining of paraesthesias and disaesthesias at four limbs associated with gait disturbances. The patient presented an IgG-, monoclonal gammopathy with normal bone marrow aspiration and elevated serum Interleukin-6 levels, fat biopsy positive for amyloid, and high anti-MAG antibodies titer (1:100000). Because of RCU, melphalan therapy was excluded and the patient is at the moment under fludarabine (25 mg/m2/day) ev for 5 days each 6 weeks for 6 bouts. [source] Neuropathy Associated With Anti-Chondroitin Sulfate C IgM AntibodiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001B Bossi Chondroitin Sulfate C (ChS-C), is a glycosaminoglycan present in the membranes of neurons and axons. Anti-ChS-C IgM antibodies have been reported in patients with predominantly sensory neuropathy (PN) often associated with IgM monoclonal gammopathy, but also in some neurological controls. In order to evaluate the frequency and clinical correlate of anti-ChS-C IgM antibodies, we tested them by a new Covalink ELISA technique in sera from 206 patients with IgM monoclonal gammopathy including 79 with PN (PN+IgM) with unknown IgM reactivity, 65 with PN with antibodies to the myelin-associated glycoprotein and 62 without PN, and from 33 patients with PN of other causes, 30 with other neurological and non-neurological diseases and 23 normal subjects. We only found high titers of anti-ChS-C IgM in two patients (1/128,000 and 1/256,000 respectively) with IgM monoclonal gammopathy: one had Waldenström Macroglobulinemia diagnosed seven years before and a 3 year history of slowly progressive limb weakness, finger paresthesias, unsteady gait and occasional nocturnal cramps. Neurological examination revealed a predominantly large-fiber sensory neuropathy with mild distal atrophy and weakness in upper and lower limbs. Electrophysiological and morphological studies were suggestive of a predominantly demyelinating neuropathy. The other patient had IgM MGUS without PN at the time of antibody testing but developed finger paresthesias seven years later, when he had decreased position sense and abnormal sensory nerve conduction studies. In conclusion high titers of anti-ChS-C IgM, though infrequent, were always associated with the presence or development of sensory PN in patients with IgM M-protein, supporting a possible role for these antibodies in the neuropathy. [source] CLINICAL, MRI, AND SKIN BIOPSY FINDINGS IN SENSORY GANGLIONOPATHIESJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2000A. Sghirlanzoni Unlike peripheral motor disorders, sensory disturbances are rarely diagnosed by the probable site of pathology. This approach is useful in the differential diagnosis between chronic sensory axonal neuropathies and ganglionopathies, in which routine clinical and neurophysiological evaluation alone often do not provide definite clues. Methods: Thirty patients with peripheral sensory disturbances were investigated. MRI was performed at cervical level in all cases. Four patients also underwent thoracic and lumbar MRI. Seventeen patients underwent skin biopsy at the proximal thigh and the distal leg. In 4 of them, further skin biopsies were taken at C5 dermatome and at the hand. Density of intra-epidermal nerve fibers (IENF) was quantified. Results: In 22 patients, sensory ganglionopathy was suspected. Disease was idiopathic in 7 cases; paraneoplastic in 3 cases; and associated with Sjögren, AIDS, autoimmune chronic hepatitis, and cisplatin neurotoxicity in 4 cases. One patient had a hereditary sensory autonomic neuropathy. Four patients had vitamin E deficiency and 3 patients a spinocerebellar syndrome. In 8 patients, sensory axonal neuropathy related to diabetes, alcoholism, and AIDS on antiretroviral treatment, and monoclonal gammopathy of undetermined significance was diagnosed. MRI findings: All ganglionopathy patients showed posterior columns hyperintensity on T2-weighted MRI. Conversely, MRI was negative in all axonal sensory neuropathy patients. Skin biopsy findings: In neuropathies, IENF density was significantly lower at the distal leg than at the proximal thigh, while ganglionopathies did not show any change with respect to the rostral:caudal orientation. A similar pattern of epidermal denervation was observed in the arm. Discussion: The degeneration of both central and peripheral sensory pathway in a fashion that is not length-dependent localizes the disease to T-shaped sensory neurons Early ataxia and cutaneous sensory symptoms involving the proximal regions of the body reflect this pattern of denervation and should prompt the diagnosis of ganglionopathy. This can be confirmed by T2-weighted hyperintensity in the posterior columns and a distinct pattern of IENF loss. [source] Chronic sensorimotor polyradiculopathy with antibodies to P2: An electrophysiological and immunoproteomic analysisMUSCLE AND NERVE, Issue 1 2008Ricard Rojas-Garcia MD Abstract In this study we report a patient with chronic progressive sensory ataxia, proximal weakness, immunoglobulin M (IgM) monoclonal gammopathy, and elevated protein levels in the cerebrospinal fluid, who showed a good response to prednisone. Electrophysiological study disclosed abnormalities predominantly of late responses (F waves and H reflexes), with no evidence of demyelination in the peripheral nerves, suggesting motor and preganglionic sensory nerve roots as the site of the lesion. An immune-mediated pathogenesis was considered and, to identify possible target antigens, we performed bidimensional electrophoresis and a Western blot study. Based on the suspected lesion site, we used human anterior and posterior root extracts. We identified IgM reactivity against peripheral nerve myelin protein P2. Enzyme-linked immunosorbent assay confirmed IgM reactivity toward one synthetic peptide from P2. To our knowledge, reactivity against P2 has not been reported previously in a paraproteinemic neuropathy. Furthermore, we demonstrated that bidimensional electrophoresis and Western blot of the tissue involved, as determined by clinical and electrophysiological studies, may be useful to establish clinical,immunological correlations in paraproteinemic neuropathies. Muscle Nerve, 2008 [source] Sensory nerve conduction deficit in experimental monoclonal gammopathy of undetermined significance (MGUS) neuropathyMUSCLE AND NERVE, Issue 6 2001Michael W. Lawlor BS Abstract An emerging body of evidence from in vitro studies and in vivo animal models supports a pathogenic role of antibodies in the development of peripheral neuropathy associated with monoclonal gammopathy of undetermined significance (MGUS). Although the assessment of motor and sensory nerve fiber function is of clinical importance, it is seldom applied experimentally. We describe the application of an electrophysiologic method for the evaluation of motor and sensory nerve fiber function using an experimental model of MGUS neuropathy. Supramaximal stimulation of the tibial nerve elicited an early motor response (M-wave, 1.7 ± 0.1 ms, n = 10) and a late sensory (H-reflex, 7.8 ± 0.1 ms, n = 10) response that was recorded from the hind foot of anesthetized rats. Intraneural injection of serum antibodies from a MGUS patient with sensorimotor polyneuropathy, but not from an age-matched control subject, produced a marked attenuation of the H-reflex (P < 0.01, n = 10) without affecting the M-wave. Light and electron microscopy of affected nerve showed myelinoaxonal degeneration with sparing of the smaller unmyelinated nerve fibers. The combined electrophysiologic and morphologic findings presented in this study are consistent with a selective sensory conduction deficit in MGUS neuropathy. Selective injury of afferent nerve fibers by this patient's serum antibodies may result from reactivity to neural antigens uniquely expressed by sensory neurons. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 809,816, 2001 [source] Serum immunoglobulin free light chain measurements and heavy chain isotype usage provide insight into disease biology in patients with POEMS syndrome,AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2010Trista Stankowski-Drengler POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) syndrome is a rare paraneoplastic syndrome in which nearly all patients have a monoclonal lambda restricted plasma cell disorder. We investigated whether patients with POEMS have abnormal serum immunoglobulin free light chain (FLC) ratios. Fifty patients with newly diagnosed POEMS syndrome were assessed. Cystatin C levels were measured to discern whether subclinical renal insufficiency could account for FLC elevations in the presence of a normal FLC ratio. Forty-five patients (90%) had elevated lambda FLC; however, only nine (18%) had abnormal FLC ratios. The rise in serum FLC of POEMS patients appeared to be multifactorial,both a function of subclinical renal insufficiency and polyclonal activation of medullary and extramedullary plasma cells. Those patients expressing a clonal IgA were more likely to have clonal plasmacytosis observed on iliac crest biopsy than those with IgG. In summary, serum immunoglobulin profiles are unique in POEMS syndrome as compared with other plasma cell disorders. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] Bortezomib effectiveness in one patient with acquired von Willebrand syndrome associated to monoclonal gammopathy of undetermined significance,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Mario Ojeda-Uribe No abstract is available for this article. [source] FOXP1 expression in monoclonal gammopathy of undetermined significance and multiple myelomaPATHOLOGY INTERNATIONAL, Issue 5 2009Petra Kora Multiple myeloma (MM) is a clonal disorder of terminally differentiated B cells. In some cases the premalignant state is monoclonal gammopathy of undetermined significance (MGUS). Neoplastic plasma cells in both entities carry multiple and complex chromosomal abnormalities that make understanding of the disease development difficult. New insight into malignant mechanisms that underlie multiple myeloma may come from forkhead box P1 transcription factor (FOXP1) analysis in neoplastic plasma cells. FOXP1 is known to be important for B-cell maturation and differentiation and could play a significant role in plasma cell tumors. The purpose of the present study was therefore to analyze FOXP1 protein presence and FOXP1 gene abnormalities in 13 cases of MGUS and 60 cases of MM. It was found that FOXP1 protein was expressed in neoplastic plasma cells, unlike in their normal counterparts, and that additional FOXP1 gene copies could be found in both MGUS and MM. Based on FOXP1 presence in MM and its role in diffuse large B-cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, FOXP1 might play an important role in plasma cell neoplasm. [source] | |||||||||||||||||||||||||||||||