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Immunoglobulin heavy chain gene rearrangement in heavy chain deposition disease suggests it is a plasma cell disease: a case report.

ABSTRACT: Heavy chain deposition disease (HCDD) is characterized by the deposition of truncated monoclonal immunoglobulin heavy chains along glomerular basement membranes. Truncated heavy chains are thought to be associated with plasma cell disease (PCD), but previous bone marrow cytology tests showed that only 30% of HCDD cases are related to PCDs. We report the first known use of immunoglobulin heavy chain (IGH) gene rearrangement to diagnose a patient with γ3-HCDD, although bone marrow morphology test identified no abnormalities. Our findings provide strong evidence for a correlation between PCDs and HCDD, which could help understand the genetic background underlying abnormal heavy chains and assess disease prognosis. Further, concordant with previous findings, bortezomib-based chemotherapy had a good therapeutic effect in our patient. We summarize the experience of diagnosing and treating a case of HCDD, and combine this with a literature review to further explore the correlation between PCDs and HCDD, which has important clinical value.

SUBMITTER: Rao Q

PROVIDER: S-EPMC8943313 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Immunoglobulin heavy chain gene rearrangement in heavy chain deposition disease suggests it is a plasma cell disease: a case report.

Rao Qingqing Q Xu Ricong R Wan Qijun Q

The Journal of international medical research 20220301 3

Heavy chain deposition disease (HCDD) is characterized by the deposition of truncated monoclonal immunoglobulin heavy chains along glomerular basement membranes. Truncated heavy chains are thought to be associated with plasma cell disease (PCD), but previous bone marrow cytology tests showed that only 30% of HCDD cases are related to PCDs. We report the first known use of immunoglobulin heavy chain (IGH) gene rearrangement to diagnose a patient with γ3-HCDD, although bone marrow morphology test ...[more]

PMID: 35301906

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Project description:BackgroundLight and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry.Case presentationWe report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain.ConclusionsThis is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.

Project description:PurposesEvidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement of immunoglobulin (Ig) gene in the circulating tumor DNA (ctDNA) is highly valuable in predicting the prognosis of patients with diffuse large B cell lymphoma (DLBCL). In this study, we investigated the role of both Ig heavy chain (IGH) and Ig kappa light chain (IGK) gene rearrangements detected in ctDNA samples in predicting DLBCL progression.MethodsNext-generation sequencing (NGS) was used to identify the dominant V(D)J clonotypic rearrangement in tissue samples of 33 DLBCL patients. Minimal residual disease (MRD) was monitored at the interim and end of the treatment, as well as the follow-up time by tracking the dominant V(D)J clonotypic rearrangement (defined as the "NGS MRD" method) in the peripheral blood (PB) ctDNA samples. The nomogram was established to predict the 12-month and 24-month progression-free survival (PFS) probability.ResultsPrior to treatment, the dominant clones identified in the tissue samples could be retrieved in tissue-matched PB of 26 (78.8%, 26/33) patients. The addition of IGK clones to IGH clones increased the MRD detection rate from 42.9% to 58.0% in the total series. NGS MRD and imaging scans showed poor concordance at the interim of treatment (Kappa = 0.24) and the follow-up time (Kappa = 0.28), and fair concordance at the end of treatment (Kappa = 0.46). However, we confirmed that the interim NGS MRD monitoring demonstrated improved prognostic performance compared to imaging scans, and both NGS MRD monitoring and imaging scans served as valuable prognostic factors for PFS at the end of treatment. Notably, NGS MRD monitoring predicted disease relapse in 3 patients prior to imaging scans. Furthermore, we found that both the faster IGH and IGK clone clearance rates were associated with favorable prognosis. The nomogram model identified IGH and IGK clone clearance rates, together with the interim NGS MRD result were the important predictors of 12-month and 24-month progression of DLBCL.ConclusionsMRD monitoring via NGS of Ig for both IGH and IGK is a promising noninvasive tool for prognosis prediction and early relapse prediction of DLBCL patients.

Dataset Information

Immunoglobulin heavy chain gene rearrangement in heavy chain deposition disease suggests it is a plasma cell disease: a case report.

Publications

Immunoglobulin heavy chain gene rearrangement in heavy chain deposition disease suggests it is a plasma cell disease: a case report.

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