Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma

Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO-LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.

Biochemical profile of multiple myeloma about 50 cases

Multiple myeloma (MM) is a clonal proliferation of plasma cells invading the bone marrow and secreting monoclonal immunoglobulin. In order to study the epidemiological and biological and biochemical characteristics of MM, we carried out a retrospective work on a cohort of 50 cases collected at the Avicenna Military Hospital in Marrakesh, during a period of 5 years (from January 2013 to December 2017). Our study included 32 men (64%) and 18 women (36%), with an average age of 60.6 years, with extremes at 44 and 87 years. The circumstances of discovery were dominated by bone pain and alteration in general condition, which are revealing in more than 65% of cases. Biologically: the sedimentation rate was accelerated in 86% of cases, a monoclonal peak appearance was revealed on serum proteins electrophoresis in 88%of cases, most often located in the γ zone (64%), a predominance of the Ig G isotype (64%), and kappa light chains in 60% of cases, Bence Jones protein (BJP) was found in 7 patients, i.e. 14% of cases, and plasmacytosis over 10% was found on the myelograms in 90 % of cases.

Monoclonal Gammapathy of Renal Significance: Morphological Variants of Lesion

The article discusses the concept of monoclonal renal gammopathy, which combines various renal diseases caused by the deposition of monoclonal immunoglobulin and / or their components in the glomeruli and tubulointerstitium. This nosological group was identified within the group of monoclonal gammopathies of undetermined significance (in 2012). The data on the study of morphological kidney damage associated with monoclonal renal gammopathy are presented. The spectrum of renal diseases in monoclonal renal gammopathy is diverse, and its classification is based on the localization of renal lesions in the glomeruli, tubules, vascular interstitium and stroma, as well as the peculiarity of the deposition of immunoglobulins (organized and unorganized). Kidney biopsy is required in most cases to locate the lesion, assess its severity, and predict patient survival. Diagnostics requires the integration of morphological changes using light microscopy, immunofluorescence, electron microscopy, and in some cases, staining of monoclonal protein for Ig isotypes is used (staining with hematoxylin / eosin, Schiff stain (PAS reaction), Jones stain, Congo Red stain, Masson’s trichromal stain). Early diagnosis and timely prescription of clone-oriented therapy by a hematologist and / or a hematooncologist can stop the progression of the malignant process and kidney malfunction. A nephrologist should monitor the patient, interacting with the hematologist.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits associated with parvovirus B19

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is included in the group of dysproteinaemias causing renal disease. Only a minority of cases are associated with a haematological malignancy. Two cases have been linked to acute parvovirus B19 infections. We report a 36-year-old African-American woman who presented with renal dysfunction, proteinuria, haematuria and a kidney biopsy reported as PGNMID with IgG3-kappa deposits. Her evaluation for a haematological malignancy was unrevealing. Her parvovirus IgM and IgG levels were positive. The patient was initially treated with an ACE inhibitor and spontaneously remitted with minimal proteinuria after 1 month. Repeat parvovirus B19 serologies 6 months later showed persistent IgG and DNA by PCR positivity but IgM negativity. Given the clinical scenario, we believe that her PGNMID was induced by acute parvovirus B19 infection, which appeared to resolve once her acute infection abated. In this report, we describe our latest understanding of PGNMID.

De Novo Sequencing of Antibody Light Chain Proteoforms from Patients with Multiple Myeloma

<p>In multiple myeloma diseases, monoclonal immunoglobulin light chains (LC) are abundantly produced, with the consequence in some cases to form deposits affecting various organs, such as kidney, while in other cases to remain soluble up to concentrations of several g.L^-1 in plasma. The exact factors crucial for the solubility of light chains are poorly understood, but it can be hypothesized that their amino acid sequence plays an important role. Determining the precise sequences of patient-derived light chains is therefore highly desirable. We establish here a novel <i>de novo</i> sequencing workflow for patient-derived LCs, based on the combination of bottom-up and top-down proteomics without database search. This pipeline is then used for the complete <i>de novo</i> sequencing of LCs extracted from the urine of 10 patients with multiple myeloma. We show that for the bottom-up part, digestions with trypsin and Nepenthes fluid extract are sufficient to produce overlapping peptides able to generate the best sequence candidates. For the sequencing of intact LC proteoforms, combining activation methods is key to achieve single amino acid resolution.</p>

De Novo Sequencing of Antibody Light Chain Proteoforms from Patients with Multiple Myeloma

<p>In multiple myeloma diseases, monoclonal immunoglobulin light chains (LC) are abundantly produced, with the consequence in some cases to form deposits affecting various organs, such as kidney, while in other cases to remain soluble up to concentrations of several g.L^-1 in plasma. The exact factors crucial for the solubility of light chains are poorly understood, but it can be hypothesized that their amino acid sequence plays an important role. Determining the precise sequences of patient-derived light chains is therefore highly desirable. We establish here a novel <i>de novo</i> sequencing workflow for patient-derived LCs, based on the combination of bottom-up and top-down proteomics without database search. This pipeline is then used for the complete <i>de novo</i> sequencing of LCs extracted from the urine of 10 patients with multiple myeloma. We show that for the bottom-up part, digestions with trypsin and Nepenthes fluid extract are sufficient to produce overlapping peptides able to generate the best sequence candidates. For the sequencing of intact LC proteoforms, combining activation methods is key to achieve single amino acid resolution.</p>