Evidence for Transition From Light Chain Deposition Disease by Immunofluorescence-Only to Classic Light Chain Deposition Disease.
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ABSTRACT:
SUBMITTER: Nasr SH
PROVIDER: S-EPMC8116763 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Light and heavy chain deposition disease (LHCDD) is a rare complication of monoclonal gammopathy. In all documented cases, LHCDD is the association of deposits of a monoclonal light chain with a normal heavy chain, especially in the kidneys. We describe here a 78-year-old woman whose renal biopsy showed nodular glomerulosclerosis, initially diagnosed as diabetic nephropathy. Detailed kidney biopsy immunofluorescence study corrected the diagnosis to ?1-?-LHCDD. Advanced immunoblot analysis showed deletion of CH1 in the both blood and kidney heavy chain. We report here, to our knowledge, the first case of ?1 LHCDD associated with a deletion of CH1.
| S-EPMC4370302 | biostudies-literature
Project description:Light-chain deposition disease (LCDD) is characterized by tissue deposition of the immunoglobulin light chains in multiple organs. These deposits appear similar to amyloid on routine sections, but differ in their staining properties and ultrastructural appearance. The deposits of LCCD are non -Congophilic and do not exhibit a fibrillar ultrastructure; while, the proteinaceous substance seen in primary amyloidosis is Congo red positive and fibrillar. One of the most common organs to be involved in LCDD is the kidney. Earlier reports on cases of LCDD have mostly shown simultaneous liver and renal involvement, there are very few cases in the literature describing LCDD of the liver without renal involvement. This report describes a patient who presented with severe cholestatic jaundice and liver cell failure with normal renal function.
| S-EPMC3282131 | biostudies-other
Project description:Patients with plasma cell dyscrasias produce free abnormal monoclonal Ig light chains that circulate in the blood stream. Some of them, termed glomerulopathic light chains, interact with the mesangial cells and trigger, in a manner dependent of their structural and physicochemical properties, a sequence of pathological events that results in either light chain-derived (AL) amyloidosis (AL-Am) or light chain deposition disease (LCDD). The mesangial cells play a key role in the pathogenesis of both diseases. The interaction with the pathogenic light chain elicits specific cellular processes, which include apoptosis, phenotype transformation, and secretion of extracellular matrix components and metalloproteinases. Monoclonal light chains associated with AL-Am but not those producing LCDD are avidly endocytosed by mesangial cells and delivered to the mature lysosomal compartment where amyloid fibrils are formed. Light chains from patients with LCDD exert their pathogenic signaling effect at the cell surface of mesangial cells. These events are generic mesangial responses to a variety of adverse stimuli, and they are similar to those characterizing other more frequent glomerulopathies responsible for many cases of end-stage renal disease. The pathophysiologic events that have been elucidated allow to propose future therapeutic approaches aimed at preventing, stopping, ameliorating, or reversing the adverse effects resulting from the interactions between glomerulopathic light chains and mesangium.
| S-EPMC7609979 | biostudies-literature
Project description:BackgroundIgD multiple myeloma (MM) is a rare subtype of MM and light chain deposition disease (LCDD) outside the kidney is also a rare and has scarcely been reported. We report herein the details of the first reported case of LCDD involving the kidney and liver co-occurring with IgD myeloma.Case presentationA 66-year-old female with IgD MM presented with rapidly progressive acute renal failure, ascites and pleural effusion. Immunofluorescent study of revealed the characteristic linear deposition of Ig? light chain along the glomerular and tubular basement membrane in kidney. Electron microscopy showed the powdery electron-dense deposits along the tubular and glomerular basement membrane consistent with the diagnosis of LCDD. Laser microdissection followed by mass spectrometry identified only Ig? light chain with more than 95% probability confirm the diagnosis of ?-LCDD but not heavy/light chain deposition disease. Liver biopsy with immunofluorescence study revealed the linear deposition of Ig? chain along the perisinusoidal space indicating the hepatic involvement of ?-LCDD. The patient was successfully treated with combination therapy with bortezomib, cyclophosphamide, dexamethasone, and daratumumab.ConclusionsThis report emphasizes that prompt biopsy of affected organs and initiation of clone directed therapy led to the correct diagnosis and favorable outcome in patient with LCDD who has extrarenal involvement.
| S-EPMC7824927 | biostudies-literature
Project description:BackgroundThis work aims to add evidence and provide an update on the classification and diagnosis of monoclonal immunoglobulin deposition disease (MIDD) and primary central nervous system low-grade lymphomas. MIDD is characterized by the deposition of light and heavy chain proteins. Depending on the spatial arrangement of the secreted proteins, light chain-derived amyloidosis (AL) can be distinguished from non-amyloid light chain deposition disease (LCDD). We present a case of an extremely rare tumoral presentation of LCDD (aggregoma) and review the 3 previously published LCDD cases and discuss their presentation with respect to AL.Case presentationA 61-year-old woman presented with a 3½-year history of neurologic symptoms due to a progressive white matter lesion of the left subcortical parieto-insular lobe and basal ganglia. 2 former stereotactic biopsies conducted at different hospitals revealed no evidence of malignancy or inflammation; thus, no therapy had been initiated. After performing physiological and functional magnetic resonance imaging (MRI), the tumor was removed under intraoperative monitoring at our department. Histological analysis revealed large amorphous deposits and small islands of lymphoid cells.ConclusionLCCD is a very rare and obscure manifestation of primary central nervous system low-grade lymphomas that can be easily misdiagnosed by stereotactic biopsy sampling. If stereotactic biopsy does not reveal a definite result, a "wait-and-see" strategy can delay possible therapy for this disease. The impact of surgical removal, radiotherapy and chemotherapy in LCDD obviously remains controversial because of the low number of relevant cases.
| S-EPMC3751626 | biostudies-literature
Project description:Cardiac amyloidosis results in an infiltrative restrictive cardiomyopathy, with a number of characteristic features: biventricular hypertrophy, abnormal myocardial global longitudinal strain with relative apical sparing, biatrial dilation, and small pericardial effusion along with conduction abnormalities. Amyloid deposits leading to hemodynamically significant valvular heart disease are very rare. We describe a rare case of concomitant moderately severe tricuspid and mitral valve stenosis because of ongoing amyloid deposition in a patient with progressive multiple myeloma and fat pad biopsy-proven light chain amyloidosis. Worsening infiltrative cardiomyopathy and valvulopathy despite evidence-based chemotherapy and heart failure pharmacotherapy led to end-stage disease and death. Valvular involvement in cardiac amyloidosis requires early recognition of the underlying disease condition to guide directed medical therapy and prevent its progression. In this instance, valvuloplasty or valve replacement is not a viable option.
| S-EPMC7261535 | biostudies-literature
Project description:Acute on chronic renal failure is a common but notably broad diagnosis. We present a 64-year-old man with a history of diastolic heart failure and chronic kidney disease, admitted for an elevated creatinine. History and physical examination were suggestive of decompensated heart failure; however, the careful interpretation of urinalysis rendered the diagnosis of multiple myeloma. On renal biopsy, the patient was found to have light chain deposition disease with cast nephropathy. Combination lesions in multiple myeloma are rare and require diligent histopathology for detection, including light microscopy, immunofluorescence and electron microscopy. These patients portray different demographics, renal manifestations, oncologic characteristics and outcomes, and hence, further studies isolating these combined lesions are warranted. Abbreviations: CKD: chronic kidney disease; CN: cast nephropathy; CT: computerized tomography; EDD: electron-dense deposits; EM: electron microscopy; IF: immunofluorescence; FLC: free light chain; LC: light chain; LCDD: light chain deposition disease; MIDD: monoclonal immunoglobulin deposition disease; MM: multiple myeloma; LM: light microscopy; NGS: nodular glomerulosclerosis; ?: kappa; ?: lambda.
| S-EPMC6737722 | biostudies-literature
Project description:That structural abnormalities may be responsible for nonamyloid immunoglobulin (Ig) light chain deposition disease (LCDD) is suggested by previous results of Ig biosynthesis studies, but this hypothesis was not documented at the molecular level. We report on the first complete primary sequence deduced from cDNA analysis of a kappa light chain responsible for LCDD associated with an apparently nonsecretory myeloma. Bone marrow myeloma cells contained intracellular kappa chains and no heavy chains by immunofluorescence. Kidney biopsy showed typical nonamyloid PAS-positive kappa chain deposits. SDS-PAGE analysis of material extracted from a kidney biopsy specimen and of Ig produced by the myeloma cells revealed kappa chains of abnormally high apparent molecular mass (30,000). Comparison of the NH2-terminal aminoacid sequence of the kappa chain deposited in the kidney and of the complete sequence of several identical kappa cDNA clones from bone marrow cells showed the identity of the tissue deposited and plasma cell kappa chain. The kappa mRNA had an overall normal structure and corresponded to the V kappa IV gene rearranged to J kappa 1 and followed by a normal constant exon of the Km(3) allotype. The variable sequence differed from the V kappa IV germline gene by nine point mutations, including an Asp----Asn substitution at position +70 resulting in a potential N-glycosylation site. In vitro biosynthesis experiments and treatment with N-glycosidase provided evidence for the intracellular glycosylation of the monoclonal kappa chain. The peculiar sequence and the glycosylation of a kappa chain of the rare V kappa IV subgroup might be responsible for structural abnormalities leading to tissue deposition.
| S-EPMC296978 | biostudies-other
Project description:B cells reactive toward phosphatidylcholine (PtC) are enriched in the B1 B cell subset, and express predominantly one of two VH/Vk combinations to confer this specificity: VH12/Vk4/5H and VH11/Vk9. Studies of transgenic mice expressing the VH12 heavy chain (VH12 mice) suggest two major checkpoints for light chain expression in this system: the first involves selection of V-J rearrangements which encode a “permissive” light chain that can functionally pair with the VH12 heavy chain; the second involves receptor editing to salvage non-PtC reactive B cells to acquire a permissive light chain that confers PtC reactivity. If this model is correct, impairing receptor editing should reduce the frequency of PtC-reactive B1 B cells in VH12 mice. To test this possibility, we bred VH12 mice to transgenic mice expressing a catalytically inactive form of RAG1 (dnRAG1 mice) which show a defect in receptor editing. Interestingly, dnRAG1 expression in VH12 mice enforces development of PtC-reactive B1 B cells, rescuing the loss of splenic B cells observed in VH12 mice. These data suggest receptor editing normally functions to remove a large portion of PtC-specific B cells in VH12 mice. Deep sequencing of the expressed light chain repertoire of PtC-reactive and non-reactive B cells in VH12 mice revealed that PtC-reactive B cells predominantly expressed the Vk4/5H (IGKV4-91) light chain gene, whereas PtC-non-reactive B cells expressed a broader, yet restricted, set of light chain genes. This analysis also revealed a low frequency of in-frame hybrid light chain genes appearing to originate via Type 2 gene replacement, which we show can originate from template switching during PCR.
2022-06-01 | GSE165776 | GEO
Project description: Not available
| S-EPMC6278990 | biostudies-literature