Light chain crystal deposition as a manifestation of plasma cell dyscrasias: The role of immunoelectron microscopy

2003 ◽  
Vol 34 (3) ◽  
pp. 270-277 ◽  
Author(s):  
Xin Gu ◽  
Roberto Barrios ◽  
Joiner Cartwright ◽  
Ramon L. Font ◽  
Luan Truong ◽  
...  
Keyword(s):  
Immunoelectron Microscopy ◽  
Plasma Cell ◽  
Light Chain ◽  
Crystal Deposition ◽  
Plasma Cell Dyscrasias

The role of CD81 for plasma cell dyscrasias

2014 ◽  
Vol 38 (3) ◽  
pp. 292-293 ◽  
Author(s):  
Mascha Binder ◽  
Ulrike Bacher
Keyword(s):  
Plasma Cell ◽  
Plasma Cell Dyscrasias

Infiltrative Nonamyloidotic Monoclonal Immunoglobulin Light Chain Cardiomyopathy: An Underappreciated Manifestation of Plasma Cell Dyscrasias

Cardiology ◽  
2000 ◽  
Vol 93 (4) ◽  
pp. 220-228 ◽  
Author(s):  
Joel N. Buxbaum ◽  
Elizabeth M. Genega ◽  
Piotr Lazowski ◽  
Asok Kumar ◽  
Paul A. Tunick ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Immunoglobulin Light Chain ◽  
Monoclonal Immunoglobulin ◽  
Plasma Cell Dyscrasias

Kidney disease and plasma cell dyscrasias: ambiguous cases solved by serum free light chain dimerization analysis

2019 ◽  
Vol 23 (6) ◽  
pp. 763-772
Author(s):  
Olga Kukuy ◽  
Batia Kaplan ◽  
Sizilia Golderman ◽  
Alexander Volkov ◽  
Adrian Duek ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Plasma Cell Dyscrasias

scholarly journals NK cells and CD38: Implication for (Immuno)Therapy in Plasma Cell Dyscrasias

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 768 ◽  
Author(s):  
Renato Zambello ◽  
Gregorio Barilà ◽  
Sabrina Manni ◽  
Francesco Piazza ◽  
Gianpietro Semenzato
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Immune System ◽  
Nk Cells ◽  
Plasma Cell ◽  
Potential Role ◽  
Myeloma Cell ◽  
Initial Reduction ◽  
Plasma Cell Dyscrasias

Immunotherapy represents a promising new avenue for the treatment of multiple myeloma (MM) patients, particularly with the availability of Monoclonal Antibodies (mAbs) as anti-CD38 Daratumumab and Isatuximab and anti-SLAM-F7 Elotuzumab. Although a clear NK activation has been demonstrated for Elotuzumab, the effect of anti-CD38 mAbs on NK system is controversial. As a matter of fact, an initial reduction of NK cells number characterizes Daratumumab therapy, limiting the potential role of this subset on myeloma immunotherapy. In this paper we discuss the role of NK cells along with anti-CD38 therapy and their implication in plasma cell dyscrasias, showing that mechanisms triggered by anti-CD38 mAbs ultimately lead to the activation of the immune system against myeloma cell growth.

scholarly journals Kidney disease associated with plasma cell dyscrasias

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1397-1404 ◽  
Author(s):  
Eliot C. Heher ◽  
Nelson B. Goes ◽  
Thomas R. Spitzer ◽  
Noopur S. Raje ◽  
Benjamin D. Humphreys ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Cell ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Light Chains ◽  
Free Light Chains ◽  
Monoclonal Immunoglobulin ◽  
Plasma Cell Dyscrasias ◽  
Made In

Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Paraproteins can cause a remarkably diverse set of pathologic patterns in the kidney and recent progress has been made in explaining the molecular mechanisms of paraprotein-mediated kidney injury. Other recent advances in the field include the introduction of an assay for free light chains and the use of novel antiplasma cell agents that can reverse renal failure in some cases. The role of stem cell transplantation, plasma exchange, and kidney transplantation in the management of patients with paraprotein-related kidney disease continues to evolve.

Knockdown of Pathologic Immuoglobulin Light Chain Protein by Small Interfering RNA Molecules.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4407-4407
Author(s):  
Jonathan E Phipps ◽  
James S Foster ◽  
Daniel P Kestler ◽  
Robert Donnell ◽  
Alan Solomon ◽  
...  
Keyword(s):  
Cell Line ◽  
Plasma Cell ◽  
Light Chain ◽  
Small Interfering Rna ◽  
Mrna Levels ◽  
Light Chain Deposition Disease ◽  
Rna Molecules ◽  
Plasma Cell Dyscrasias ◽  
Rpmi 8226 ◽  
Interfering Rna

Abstract Abstract 4407 Introduction A major contributing factor to the morbidity and mortality of patients with plasma cell dyscrasias (i.e., light chain deposition disease, light chain amyloidosis (AL), etc.) is the overproduction and deposition of immunoglobulin light chain (LC) protein. Accumulation of insoluble fibrillar or amorphous aggregates within vital organs, particularly the kidneys, contributes to progressive loss of function and failure. Recent reports have shown that reducing levels of precursor LC proteins by 50% correlated with improved prognosis in patients with AL. Current therapies to suppress the production of monoclonal free LC rely on conventional or high dose myeloablative chemotherapeutic intervention. These therapies carry inherent risk and may not be appropriate in every situation, thus there is a need to employ alternative or adjuvant therapeutic approaches. To this end, we have investigated the ability of small interfering RNA molecules to decrease production of LC mRNA and protein secretion in both a synthetic and naturally occurring myeloma cell line. We report here that exposure of these lines to small interfering RNA (siRNA) oligonucleotides inhibited LC production in a specific and non-cytotoxic manner. Methods SP2/O mouse myeloma cells were stably transfected with a construct encoding a human λ6 LC protein (Wil) and designated SP2/O-1 for this study. The human λ2 producing cell line RPMI 8226 was purchased from ATCC. For both lines, LC mRNA was sequenced and used to design siRNA molecules targeting the V-, J-, or C-region of the LC. Cells were cultured for 1-3 d with sequence-specific siRNA, sham siRNA, or with media alone after which time LC mRNA levels were assessed by real-time PCR, and cellular or secreted LC protein concentrations were measured using flow cytometry or ELISA, respectively. Results Treatment with siRNA was well tolerated and no significant reduction in cell viability was observed in either the SP2/O-1 or RPMI 8226 cells at any of the timepoints assayed. Exposure of either SP2/O-1 or 8226 cells to siRNAs targeting the LC resulted in reductions of mRNA as compared to sham siRNA-treated controls. Flow cytometric analysis of 8226 cells immunostained with anti-LC antibodies at 48 h post transfection, indicated that ∼63% and 83% of the total cell number contained reduced amounts of cytoplasmic LC following treatment with V-, or C- region-specific siRNA, respectively. The 8226 LC protein was also significantly reduced by 20-60% in culture supernatants over the 72h period in cells exposed to experimental siRNAs as compared with sham-treated cells. Similarly, treating the SP2/O-1 cells with siRNAs led to significant (20-52%; P < 0.05) reductions in secreted LC Wil over 72 h as compared to sham-siRNA treatments. Conclusions We demonstrate here that siRNA provides a viable option for preventing the synthesis and thus secretion of pathologic LC protein using two cell lines, and that this reduction is carried out in a specific and non-cytotoxic manner. These results provide support for the potential use of siRNA to decrease the secretion of pathologic LC proteins in patients diagnosed with plasma cell dyscrasias. Our future goal will be to evaluate the action of siRNAs on LC production in vivo using a murine model of the disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Is accuracy of serum free light chain measurement achievable?

2016 ◽  
Vol 54 (6) ◽  
Author(s):  
Joannes F.M. Jacobs ◽  
Jillian R. Tate ◽  
Giampaolo Merlini
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Clinical Consequence ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Quantitative Monitoring ◽  
Plasma Cell Disorders ◽  
Prognostic Stratification ◽  
Plasma Cell Dyscrasias

AbstractThe serum free light chain (FLC) assay has proven to be an important complementary test in the management of patients with monoclonal gammopathies. The serum FLC assay has value for patients with plasma cell disorders in the context of screening and diagnosis, prognostic stratification, and quantitative monitoring. Nonetheless, serum FLC measurements have analytical limitations which give rise to differences in FLC reporting depending on which FLC assay and analytical platform is used. As the FLC measurements are incorporated in the International Myeloma Working Group guidelines for the evaluation and management of plasma cell dyscrasias, this may directly affect clinical decisions. As new certified methods for serum FLC assays emerge, the need to harmonise patient FLC results becomes increasingly important. In this opinion paper we provide an overview of the current lack of accuracy and harmonisation in serum FLC measurements. The clinical consequence of non-harmonized FLC measurements is that an individual patient may or may not meet certain diagnostic, prognostic, or response criteria, depending on which FLC assay and platform is used. We further discuss whether standardisation of serum FLC measurements is feasible and provide an overview of the steps needed to be taken towards harmonisation of FLC measurements.

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