Immunoglobulin light chain alters mesangial cell calcium homeostasis

1997 ◽  
Vol 272 (3) ◽  
pp. F319-F324 ◽  
Author(s):  
L. Zhu ◽  
G. A. Herrera ◽  
C. R. White ◽  
P. W. Sanders
Keyword(s):  
Calcium Homeostasis ◽  
Light Chain ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Calcium Influx ◽  
Light Chains ◽  
Kappa Light Chain ◽  
Immunoglobulin Light Chains ◽  
Acetoxymethyl Ester ◽  
Cell Calcium

This study examined the hypothesis that certain immunoglobulin light chains directly altered mesangial cell calcium homeostasis. Intracellular Ca2+ concentration (intracellular [Ca2+]) signaling was determined in suspensions of rat mesangial cells using the acetoxymethyl ester of fura 2 with a calcium removal/replacement protocol. Pretreatment of cultured rat mesangial cells with a glomerulopathic kappa-light chain (gle) produced reversible dose- and time-dependent attenuation of ATP- and thrombin-evoked [Ca2+] transients (189 +/- 24 vs. 126 +/- 10 nM, P < 0.05 with ATP; 198 +/- 5 vs. 117 +/- 3 nM, P < 0.05 with thrombin) and capacitative calcium influx (199 +/- 14 vs. 142 +/- 17 nM, P < 0.05 for ATP; 252 +/- 19 vs. 198 +/- 18 nM, P < 0.05 for thrombin). Mesangial cells treated with gle and supplemented with myo-inositol (450 microM) did not demonstrate the attenuation of the ATP-evoked [Ca2+] transient and capacitative calcium influx. Gle also decreased mean [Ca2+] transient (80 +/- 7 vs. 56 +/- 1 nM, P < 0.05) and capacitative calcium influx (306 +/- 10 vs. 241 +/- 4 nM, P < 0.05) in response to thapsigargin, a Ca2+-adenosinetriphosphatase inhibitor. This inhibition was not reversed by exogenous myo-inositol. Another kappa-light chain (10 microg/ml) did not affect mesangial cell calcium signaling. Deranged mesangial cell calcium homeostasis by certain light chains may play a central pathogenetic role in glomerulosclerosis associated with deposition of immunoglobulin light chains.

scholarly journals Complete Primary Sequences of Two λ Immunoglobulin Light Chains in Myelomas with Nonamyloid (Randall-Type) Light Chain Deposition Disease

1998 ◽  
Vol 153 (1) ◽  
pp. 313-318 ◽  
Author(s):  
Catherine Decourt ◽  
Guy Touchard ◽  
Jean-Louis Preud'homme ◽  
Ruben Vidal ◽  
Hélène Beaufils ◽  
...  
Keyword(s):  
Light Chain ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Light Chain Deposition

scholarly journals Stabilization of amyloidogenic immunoglobulin light chains by small molecules

2019 ◽  
Vol 116 (17) ◽  
pp. 8360-8369 ◽  
Author(s):  
Gareth J. Morgan ◽  
Nicholas L. Yan ◽  
David E. Mortenson ◽  
Enrico Rennella ◽  
Joshua M. Blundon ◽  
...  
Keyword(s):  
Small Molecules ◽  
Light Chain ◽  
Cardiac Involvement ◽  
Plasma Cells ◽  
Full Length ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
X Ray ◽  
Tissue Degeneration ◽  
Dimerization Interface

In Ig light-chain (LC) amyloidosis (AL), the unique antibody LC protein that is secreted by monoclonal plasma cells in each patient misfolds and/or aggregates, a process leading to organ degeneration. As a step toward developing treatments for AL patients with substantial cardiac involvement who have difficulty tolerating existing chemotherapy regimens, we introduce small-molecule kinetic stabilizers of the native dimeric structure of full-length LCs, which can slow or stop the amyloidogenicity cascade at its origin. A protease-coupled fluorescence polarization-based high-throughput screen was employed to identify small molecules that kinetically stabilize LCs. NMR and X-ray crystallographic data demonstrate that at least one structural family of hits bind at the LC–LC dimerization interface within full-length LCs, utilizing variable-domain residues that are highly conserved in most AL patients. Stopping the amyloidogenesis cascade at the beginning is a proven strategy to ameliorate postmitotic tissue degeneration.

IgD myeloma protein with "unreactive" light chain determinants.

1979 ◽  
Vol 25 (8) ◽  
pp. 1495-1498 ◽  
Author(s):  
J Cejka ◽  
K Kithier
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Light Chains ◽  
Precipitation Reaction ◽  
Immunoglobulin Light Chains ◽  
Myeloma Protein ◽  
Monoclonal Protein ◽  
Immunofixation Electrophoresis ◽  
Intact Molecule

Abstract Serum from a patient with multiple myeloma showed a monoclonal protein, classified by immunoelectrophoresis as IgD. Immunofixation electrophoresis and immunoelectrophoresis failed to demonstrate a precipitation reaction between the paraprotein and antisera to immunoglobulin light chains. The light chains of the monoclonal protein, immunologically inaccessible in the intact molecule, reacted with anti-lambda chain antisera only after reduction and alkylation of the paraprotein. Moreover, interpretation of the immunoelectrophoretic patterns was hampered by the presence in patient's serum of free lambda chains having about the same mobility as that of the paraprotein.

High-Dose Melphalan and Autologous Stem Cell Transplantation in Unusual Non-Amyloid Light Chain Deposition Disorders.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5476-5476
Author(s):  
Karin I. Weichman ◽  
David C. Seldin ◽  
Karen Quillen ◽  
Michael Rosenzweig ◽  
Laura M. Dember ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cell ◽  
Light Chain ◽  
Light Chains ◽  
Plasma Cell Dyscrasia ◽  
High Dose ◽  
Kappa Light Chain ◽  
Light Chain Deposition

Abstract Light chain deposition disease (LCDD) is caused by a clonal plasma cell disorder in which fragments of monoclonal immunoglobulin light chains, usually with a kappa genotype, are deposited in various tissues in a globular form resulting in organ dysfunction. Crystal-storing histiocytosis (CSH) is another light chain deposition disorder in which monoclonal light chains form intracytoplasmic crystalline deposits. Both LCDD and CSH are uncommon diseases, for which there is limited treatment experience. However, conventional anti-plasma cell chemotherapy with oral melphalan as is used in multiple myeloma has been tried in LCDD with little benefit. Between 1999–2005, five patients with LCDD and one patient with CSH have been treated at Boston University Medical Center with high-dose intravenous melphalan (IVM) followed by autologous peripheral blood stem cell transplantation (SCT). Patients have been treated with either 200mg/m2 of IVM (n=5) or 140 mg/m2 (n=1) depending on age and clinical status and subsequently have been assessed for hematologic responses and for improvements in organ function at 3, 6 and 12 months, and annually thereafter. The median age of patients at the time of treatment has been 45 years (range 34–51). Four patients with LCDD had kappa light chain deposition involving the kidneys and 1 of these patients had extrarenal involvement of the heart on electron microscopy of endomyocardial biopsy as well. One patient with LCDD had lambda deposition involving kidneys only. The patient with CSH had only renal involvement, with kappa light chain plasma cell dyscrasia. All except 1 patient had impaired renal function with creatinine clearance ranging from 21 – 64 ml/min. All treated patients are alive and well at a median follow up of 13.6 months (range 5–24 months). Median survival has not yet been reached. No treatment-related deaths were noted, and treatment-related toxicities were manageable and reversible. All evaluable patients (n=4) have achieved a hematologic complete response of the underlying plasma cell dyscrasia after IVM/SCT. In conclusion, this experience indicates that IVM/SCT is a safe, feasible, and effective modality for the treatment of these unusual light chain deposition disorders.

Aggressive Light Chain Amyloidosis Cases have Unstable Immunoglobulin Light Chains

2004 ◽  
pp. 55-57
Author(s):  
L. A. Sikkink ◽  
E. M. Baden ◽  
S. R. Vance ◽  
K. J.-L. Riley ◽  
A.T. Moch ◽  
...  
Keyword(s):  
Light Chain ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
Light Chain Amyloidosis

Light chain proximal tubulopathy with cast nephropathy in monoclonal gammopathy of renal significance

2020 ◽  
Vol 13 (6) ◽  
pp. e234361
Author(s):  
Rebaika Chopra ◽  
Rosalba Santana de Roberts ◽  
Ibrahim Batal ◽  
Sachin Batra ◽  
Belinda Jim
Keyword(s):  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Fanconi Syndrome ◽  
Cell Damage ◽  
Biochemical Properties ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
Cast Nephropathy ◽  
Proximal Tubulopathy ◽  
Light Chain Proximal Tubulopathy

Kidney tubular disorders due to monoclonal immunoglobulin light chains are common manifestations of B-cell neoplasm. Cast nephropathy (CN) is the most frequent type of these disorders and may present with acute kidney injury (AKI) due to the presence of excess light chains in the distal tubules. Light chain proximal tubulopathy (LCPT) is an uncommon form of renal disease and may present as Fanconi syndrome due to proximal tubular cell damage by intracellular deposition of light chains. The concomitant disorder of both CN and LCPT is rare given the inherent differences in the biochemical properties of the immunoglobulin light chains of each disorder. We report a 64-year-old man who presented with AKI and Fanconi syndrome who was discovered to have both CN and LCPT due to the underlying disorder of monoclonal gammopathy of renal significance and who has responded favourably with conventional chemotherapy. We also review the existing literature on this interesting subject.

Vasoactive agents affect mesangial cell adhesion

1986 ◽  
Vol 251 (4) ◽  
pp. C505-C511 ◽  
Author(s):  
J. I. Kreisberg ◽  
M. A. Venkatachalam
Keyword(s):  
Cell Adhesion ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Mesangial Cell ◽  
Cultured Cells ◽  
Mesangial Cells ◽  
Stress Fibers ◽  
Vasoactive Agents ◽  
Substrate Adhesion ◽  
Adhesive Contacts

The formation and maintenance of stress fibers in cultured mesangial cells is associated with myosin light chain phosphorylation [Kreisberg et al. Am. J. Physiol. 249 (Renal Fluid Electrolyte Physiol. 18): F227-F235, 1985], a biochemical indicator for activation of actin-myosin interactions. Agents that elevate intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) (e.g., isoproterenol) fragment stress fibers and cause myosin light chain dephosphorylation, whereas the addition of contractile agents such as arginine vasopressin (AVP) and prostaglandin E2 (PGE2) reverses these changes. Because stress fiber development in cultured cells is correlated with tight cell to substrate adhesion, we wanted to examine whether vasoactive agents have an effect on mesangial cell adhesion. Both isoproterenol and dibutyryl cAMP (DBcAMP) reduced mesangial cell adherence as measured by a trypsin assay (% detached cells: control 11 +/- 2.4%; isoproterenol plus isobutylmethylxanthine (IBMX) = 48.3 +/- 7.4%; DBcAMP = 29.3 +/- 3.7%; DBcAMP-IBMX = 73 +/- 4.4%). The areas of focal (adhesive) contacts between the cell and substratum as observed by interference-reflexion microscopy were also reduced, being replaced by areas of greater separation (% of the surface in contact with the substratum: control = 7.4 +/- 0.8%; isoproterenol-IBMX = 2.9 +/- 1.1%). Addition of PGE2 or AVP to the incubation medium containing the cAMP-elevating agents prevented the above changes. PGE2 or AVP alone increased mesangial cell adhesion (% detached cells: control 11 +/- 2.4%; PGE2 = 6.8 +/- 0.5%; AVP = 5.1 +/- 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatric and Perinatal Reference Intervals for Immunoglobulin Light Chains Kappa and Lambda

1992 ◽  
Vol 38 (4) ◽  
pp. 548-550 ◽  
Author(s):  
K R Herkner ◽  
H Salzer ◽  
A Böck ◽  
A Mühl ◽  
T Tsaka ◽  
...  
Keyword(s):  
Light Chain ◽  
Reference Intervals ◽  
Linear Increase ◽  
Light Chains ◽  
Serum Concentrations ◽  
Immunoglobulin Light Chains ◽  
Adult Type ◽  
Mean Values ◽  
Age Related ◽  
Chain Analysis

Abstract In routine analysis for immunoglobulin light chains in pediatric diagnostics, the age-related reference intervals for serum kappa (kappa) and lambda (lambda) light chains were evaluated in 1543 healthy subjects (newborns to age 16 years, including 168 premature infants). Light-chain analysis was performed by rate nephelometry. IgG, IgA, and IgM were measured simultaneously, and heavy- and light-chain differences were calculated for control purposes. Results for IgG, IgA, and IgM generally agreed with reference intervals reported in the literature. kappa showed age-related changes comparable with changes in IgG concentrations, whereas lambda showed moderate fluctuations. The kappa/lambda ratio showed an almost linear increase with age, starting with 0.97 at four months and reaching the highest value of 2.21 at 15 years (mean values). Preterm infants presented with markedly low serum concentrations of IgG and corresponding light chains but with adult-type kappa/lambda ratios because of the maternal-origin IgG.

Sign in / Sign up

Export Citation Format

Share Document