Paraprotein

The term monoclonal gammopathies of renal significance (MGRS) encompasses a group of renal histopathological lesions fulfilling two criteria: (a) they are caused by nephrotoxic monoclonal immunoglobulins and (b) the monoclonal immunoglobulins are produced by small B-cell or plasma cell clones which do not meet the criteria for multiple myeloma or malignant lymphoma. Here, we provide a review of the MGRS definition and related terminology and elaborate on the diagnostic approach and treatment principles from the general physician perspective...

Serum electrophoresis (SPEP) is a method used to analyze the distribution of the most important proteins in the blood. The major clinical question is the presence of monoclonal fraction(s) of antibodies (M-protein/paraprotein), which is essential for the diagnosis and follow-up of hematological diseases, such as multiple myeloma. Recent studies have shown that machine learning can be used to assess protein electrophoresis by, for example, examining protein glycan patterns to follow up tumor surgery. In this study we compared 26 different decision tree algorithms to identify the presence of M-proteins in human serum by using numerical data from serum protein capillary electrophoresis...

Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy...

BACKGROUND: Paraproteins can interfere with several substances, producing erroneous laboratory measurements. The diagnosis of kidney disease in patients with hematological disorders has important prognosis implications. An elevated creatinine with no other signs of kidney disease should prompt the idea of a spurious creatinine. Communication between the clinical team and the laboratory is key. CASE PRESENTATION: In this case, we present a 68-year-old woman with an elevated creatinine and an IgM lambda paraprotein...

BACKGROUND: This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma (MM) during the induction phase of treatment with bortezomib, cyclophosphamide, and dexamethasone (BCD). METHODS: We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front-line regimen at Peking Union Medical College Hospital from January 1, 2013 to December 31, 2018. RESULTS: There were 107 patients with International Staging System (ISS) III and 51 with paraprotein of light chain...

BACKGROUND Non-IgM lymphoplasmacytic lymphoma (LPL) is a rare subtype of LPL, constituting less than 5% of the cases, and is often associated with IgG, IgA, or light chain paraproteins and is rarely a non-secretor. Non-IgM LPL remains poorly studied, and the differential diagnosis from other small B-cell lymphomas with plasmacytic differentiation and plasma cell neoplasm is challenging. CASE REPORT A 67-year-old woman presented with weight loss, persistent anemia, and borderline leukopenia. Serum protein electrophoresis and immunofixation demonstrated a faint IgG and kappa band against a dense polyclonal background...

BACKGROUND:  We report the case of a 59-year-old multiple myeloma patient in whom an anti-human thrombin IgA antibody led to prolonged in vitro coagulation times, suggesting inhibitors to all intrinsic coagulation factors in the absence of spontaneous bleeding. METHODS:  Routine and extensive special coagulation tests, in vivo bleeding time, and specific antibody testing were performed. RESULTS:  Although the patient did not suffer from spontaneous bleeding and had a normal in vivo bleeding time, the anti-human thrombin IgA autoantibody affected all coagulation assays involving human thrombin in vitro, mimicking inhibitors to intrinsic coagulation factors...

OBJECTIVE: Calprotectin (CLP), S100A6, and High Mobility Group Nucleosome-Binding Protein 1 (HMGN1), known as alarmins, are involved in the pathogenesis of many tumors. In this study, we aimed to inve stigate the relationship of serum CLP, S100A6, and HMGN1 levels with clinical and laboratory findings in Multiple Myeloma (MM) patients and their role in the pathogenesis of MM. MATERIALS AND METHODS: We measured serum CLP, S100A6, and HMGN1 levels in 55 newly diagnosed patients and 32 healthy controls (HC)...

Waldenström's disease is a rare lymphoproliferative syndrome in the bone marrow and sometimes in lymphoid organs which secretes high amounts of monoclonal immunoglobulin M into serum. It can remain indolent for years and rarely affects the kidney, with intraglomerular rather than intratubular damage being predominant, in contrast to multiple myeloma. Different studies identified AL amyloidosis as the most frequent renal lesion, followed by cryoglobulinemic glomerulonephritis. Signs and symptoms may be unspecific, as well as renal manifestations, so collaboration between nephrologists, hematologists, and pathologists is crucial to establish the role of paraprotein in the development of renal damage...

Scleredema adultorum of Buschke is an important differential diagnosis in sclerosing diseases. Diagnosis is based on the typical histology with mucin deposits and grossly increased dermal width and a clinical presentation of diffuse non-pitting induration of the skin starting at the nape of the neck and interscapular region extending to shoulders and upper thorax, causing dysmobility due to dermal stiffness. Even though the pathogenesis remains unclear, three subtypes can be distinguished: association with infections, paraproteins, or most frequently with diabetes mellitus...

BACKGROUND: Serum Protein Electrophoresis (SPE) is crucial for the diagnosis and follow-up of monoclonal gammopathy (MG), as it helps to separate and identify these paraproteins. Currently, Pakistan lacks standardized guidelines for SPE reporting and analytical performance. This survey aims to analyze reporting variations from Consultant Chemical Pathologists in Pakistani laboratories. METHODS: This cross-sectional survey was conducted by the section of Chemical Pathology, Department of Pathology and Laboratory Medicine, at Aga Khan University Hospital, Karachi...

BACKGROUND: Intravenous immunoglobulin (IVIG) and rituximab are considered the first-line and second-line treatments for Chronic Ataxic Neuropathy and Ophthalmoplegia with IgM-paraprotein, cold Agglutinins, and anti-Disialosyl antibodies (CANOMAD), with an overall clinical response around 50%. New anti-CD38 daratumumab, targeting long-lived plasma cells, has been reported as a promising therapy for treatment-refractory antibody-mediated disorders. We report the first case of a severe refractory CANOMAD, successfully treated with daratumumab...

RATIONALE: Splenic marginal zone lymphoma (SMZL), an indolent small B-cell lymphoma, is uncommon, and part of the patients exist plasmocytic differentiation and secrete monoclonal paraproteins including IgM predominantly. SMZL with monoclonal IgG is rarer. PATIENT CONCERNS: We report a case of SMZL (49-year-old, male) with monoclonal IgG, MYD88L265P mutation and hepatitis B virus infection. DIAGNOSES: The patient was presented to our hospital with aggravating complaints of dizziness, fatigue, postprandial abdominal distension, and night sweats...

Plasma cell leukemia (PCL) is a clinically aggressive variant of multiple myeloma, characterized by a high burden of circulating plasma cells, necessitating swift and accurate diagnosis due to its poor prognosis. The conventional diagnostic criteria, including the recent recommendation by the International Myeloma Working Group (IMWG) of > 5% circulating plasma cells as positive, have evolved over time. In this context, we present a detailed case report that underscores the pivotal role of the ADVIA 2120 automated hematology counter in detecting plasma cells through cytogram analysis, along with the significance of routine peripheral blood smear analysis and the utility of a large unstained cells (LUCs) threshold of > 4...

Immunoglobulin (Ig) isotype switching in multiple myeloma (MM) is a rare form of clonal evolution. The aim of this study was to investigate the clinical features and prognostic significance of Ig isotype switching by observing Ig transformation in patients with relapse. A retrospective analysis was performed on 506 patients with newly diagnosed MM who were treated at our hospital from February 2005 to February 2020. The patients who experienced relapse were divided into the following four groups according to Ig phenotype: original paraprotein, complete isotype switching, light chain escape (LCE),and non-secretory clinical relapse...

Monoclonal gammopathy of uncertain significance associated acquired von Willebrand syndrome is a serious bleeding condition driven by immunological clearance of von Willebrand factor and has limited treatment options. We present a patient who achieved durable remission through eradication of the monoclonal paraprotein with clonal directed therapy with bortezomib.

Bisalbuminemia is a rare, benign, protein anomaly presenting with two distinct peaks of albumin on serum protein electrophoresis. It reflects the presence of a normal albumin and a modified albumin in the same individual. This condition can be either hereditary or acquired. Bisalbuminemias are more frequently encountered when serum protein electrophoresis is performed with capillary technique, because this offers better resolution compared to the conventional gel electrophoresis. There are very few case reports available in the literature, showing the presence of a bifid albumin peak along with a distinct paraprotein peak in the globulin region in serum protein electrophoresis...

The purpose of this article is to evaluate the course of paraproteinemic keratopathy (PPK) in patients undergoing systemic therapy for the underlying hematological disease. Baseline and follow-up examinations included hematological work-up, best-corrected visual acuity, slit-lamp biomicroscopy, and in vivo confocal laser scanning microscopy (IVCM). We included 22 patients with bilateral PPK (aged 68 ± 10.4 years, 11 males). Ten patients with multiple myeloma (MM) underwent on-label systemic therapy. During follow-up, we observed a regression of corneal opacities in three patients under slit-lamp examination and under IVCM, while PPK remained unchanged in seven patients...

BACKGROUND: Multiple myeloma (MM) is an incurable hematological malignancy of the plasma cells. The maintenance of protein homeostasis is critical for MM cell survival. Elevated levels of paraproteins in MM cells are cleared by proteasomes or lysosomes, which are independent but inter-connected with each other. Proteasome inhibitors (PIs) work as a backbone agent and successfully improved the outcome of patients; however, the increasing activity of autophagy suppresses the sensitivity to PIs treatment...

BACKGROUND/AIM: Waldenström's macroglobulinemia (WM) is a rare slow-growing B-cell lymphoma that is characterized by lymphoplasmacytic bone marrow infiltration and the production of monoclonal immunoglobulin M (IgM) paraprotein. In 5-10% of patients, WM undergoes transformation into diffuse large B-cell lymphoma (DLBCL), which is more aggressive, with poor prognosis and a low survival rate. CASE REPORT: Α 69-year-old woman was diagnosed with WM in 2009...