Huge discrepancy between serum immunoglobulin concentration and proteinemia due to heavy chain disease.

Immunoassays are widely used in clinical laboratories because of their ease of use and low cost. These tests are based on antigen-antibody binding. However, clinicians and laboratory personnel may be confronted with immunoassay interference leading to difficulties in medical care. Here, we report a huge analytical discrepancy with IgG concentration higher than proteinemia in a 75-year-old man. Serum electrophoresis and immunofixation diagnosed γ-heavy chain disease. After investigation by different methods, the assay discrepancy was still present. We hypothesize that the interference is related to the truncated immunoglobulin secreted by the lymphoproliferative disorder.

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

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.

[Biological difficulties of a heavy chains disease diagnosis]. / Difficultés biologiques d'un diagnostic de maladie des chaînes lourdes.

Heavy chain diseases are rare gammopathies characterized by the production of a truncated heavy chain monoclonal immunoglobulin without associated light chain. These hemopathies, which are frequently associated with immunological or hematological disorders, are clinically closer to lymphomas than to myelomas. The case that we report illustrates the difficulty to characterize a heavy chain gammopathy discovered in an elderly woman admitted in the department of internal medicine for alteration of general condition.

Immunoglobulin A Heavy Chain Deposition Disease: A Case Report.

Monoclonal immunoglobulin deposition disease (MIDD) is a rare disease characterized by the non-fibrous deposition of monoclonal immunoglobulin molecules along the glomerular or tubular basement membrane in kidney. We report herein the details of one case of heavy chain deposition disease (HCDD) diagnosed by renal biopsy, a relatively rare subtype of MIDD. DOI: 10.52547/ijkd.6484.

Gamma heavy chain disease associated with rheumatoid arthritis: a case report.

BACKGROUND: Gamma heavy chain disease (γ-HCD) is a monoclonal gammopathy defined by an abnormal clonal and isolated production of incomplete heavy chain gamma (γ), unable to bind with light chains kappa or lambda. This disease is rare and remains poorly described. Its association to lymphoid neoplasm is well established, but exceptional forms of γ-HCD may also accompany auto-immune diseases. We report here a new case of γ-HCD characterized by an indolent course with a 4-year follow-up, and its association with quiescent rheumatoid arthritis (RA). CASE PRESENTATION: We report the case of a 85-year old French white man followed for quiescent anti-CCP+ rheumatoid arthritis treated by prednisolone 4 mg/day and hydroxychloroquine 200 mg/day since 10 years, and a monoclonal gammopathy of undetermined significance for 6 years, who was hospitalized for costal fractures after a fall. Serum protein electrophoresis showed a stable small monoclonal peak, and capillary electrophoresis/immunosubtraction technique identified an isolated clonal γ-heavy chain (HC). Bone marrow aspiration was normal and he had no other lymphoproliferation. The monoclonal peak remained stable after 4 years of follow-up. CONCLUSIONS: In case of monoclonal peak without complete monoclonal Ig on serum protein electrophoresis, the diagnosis of γ-HCD should be discussed and capillary electrophoresis/immune-subtraction is a mean to detect isolated monoclonal heavy chain (HC). Gamma-HC disease is rare, may be associated to RA, and may have an indolent course.

Gamma-heavy chain disease.

BACKGROUND: Gamma-heavy chain disease is a rare disease, described so far in approximately 150 cases. The aim of this work was laboratory dia-gnostics of immunoglobulin heavy chain disease. MATERIALS AND METHODS: A 60-year-old patient was referred to the University Hospital in Ostrava for suspected marginal zone lymphoma from gastric bio-psy. Staging examinations including bone marrow trepanobio-psy and PET/CT were added; special examinations required serum protein electrophoresis, immunofixation electrophoresis, determination of polyclonal immunoglobulins, free light chains, and immunoglobulin heavy/light chain pairs. Isoelectric focusing in agarose gel followed by affinity immunoblotting and SDS electrophoresis was added due to unclear findings. RESULTS: 0.1 % of plasma cells were found in the bone marrow, of which 87 % were clonal (pathological) plasma cells, followed by the cyt cytotype LAMBDA + CD38 + CD138 + CD45 + CD19 + CD56- CD27 + CD81- CD117-. Monoclonal heavy chains were found in the patients serum. No monoclonal immunoglobulin heavy or light chains were detected in urine. The PET/CT examination showed generalized lymphadenopathy, splenomegaly and inhomogeneous accumulation of fluorodeoxyglucose in axillary and appendicular skeleton, but without the presence of typical osteolytic lesions. CONCLUSION: Monoclonal heavy chains of immunoglobulins are a rare disease. In contrast to the detection of a complete paraprotein molecule, additional methods must be used to confirm them. The finding of monoclonal heavy chain gamma in the serum of the study patient is related to the presence of marginal zone lymphoma, which was proven from a gastric bio-psy. The study was supported by the project of MH CZ - DRO - FNOs /2017 (Biobank in Teaching Hospital Ostrava) The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Identification of gamma heavy chain disease using MALDI-TOF mass spectrometry.

We describe the use of MALDI-TOF mass spectrometry in the analysis of a suspected case of gamma heavy chain disease. The patient had an abnormal serum immunofixation result where a monoclonal gamma heavy chain band was present without a corresponding light chain. Analysis by MALDI-TOF mass spectrometry revealed large peaks in the spectrum following IgG-specific purification. The m/z values of the peaks were outside the expected range for normal heavy chains or light chains. Corresponding peaks were not present in mass spectra of the kappa- or lambda-specific purifications. MALDI-TOF MS confirmed the presence of a truncated heavy chain without associated light chains. This case report demonstrates the value of mass spectrometry in interpreting challenging cases such as the identification of heavy chain disease.

Cutis laxa for diagnosis of γ1-heavy-chain deposition disease: Report of four cases.

Heavy-chain deposition disease (HCDD) is characterized by tissue deposits of a truncated monoclonal immunoglobulin heavy-chain (HC) on basement membranes. Diagnosis is usually made on kidney biopsy, showing nodular glomerulosclerosis with HC deposits which can be missed, resulting in delay in diagnosis. We report four γ1-HCDD patients presenting with cutis laxa, hypocomplementemia and hypoalbuminemia. In two patients, unsuspected HCDD was revealed by cutis laxa and diagnosis was made on skin biopsy. In all patients, serum albumin and complement represented surrogate markers for disease monitoring. In γ-HCDD, extrarenal manifestations such as cutis laxa may precede renal injury and are precious tools for an early diagnosis, which is crucial to avoid progression of irreversible renal and elastic tissue damage.

Gamma heavy-chain disease accompanied with follicular lymphoma: a case report.

Heavy chain diseases (HCD) are B-cell lymphoprolipherative disorders characterized by the production of monoclonal heavy chains without associated light chains. Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm. The monoclonal component is not always detectable by serum electrophoresis, and often an immunofixation procedure is necessary to detect this component. Prognosis is variable, and no established guidelines for follow-up are available. We describe a case of a challenging diagnosis of γ-HCD due to the absence of clinical signs frequently reported in the disease (anaemia and palatal oedema among others). Haematological malignancy was the first suspicion but bone marrow examination was negative. In addition, the presence of an autoimmune bicytopenia and a Klinefelter syndrome complicated the clinical context of the patient. A thoracoabdominal computed tomography reported many small adenopathies whose pathological and immunohystochemical study revealed a follicular lymphoma. Shortly after, serum inmunofixation secondary to an abnormal electrophoretic pattern revealed a gamma paraprotein without light chains. Eventually, γ-HCD in association with follicular lymphoma was the final diagnosis. This is the first case reporting this association.

Long-term renal survival of γ3-heavy chain deposition disease: a case report.

BACKGROUND: Monoclonal immunoglobulin deposition disease (MIDD) is characterized by the non-amyloid deposition of monoclonal immunoglobulin fragments in the basement membranes. Heavy chain deposition disease (HCDD) is a type of MIDD. HCDD is an extremely rare disease, and only three cases have been reported in Japan up to the present. The prognosis of HCDD is very poor, and optimal treatment has not been established. Only a few cases of HCDD with favorable long-term renal prognosis have been reported to date. CASE PRESENTATION: The authors describe a 61-year-old woman who presented with massive proteinuria, progressive kidney impairment, and hypocomplementemia. Kidney biopsy was performed for a precise diagnosis. On light microscopy, glomerules were lobulated and presented with nodular sclerosing glomerulopathy with membranoproliferative glomerulonephritis-like features. Immunofluorescence studies were positive for IgG, C3, and C1q within the mesangial nodules and in a linear distribution along the capillary walls without associated deposition of light chains. Staining for IgG showed the presence of linear deposits along tubular basement membranes. The analysis of the IgG subclass stain demonstrated intense positivity for IgG3 only. Electron microscopy revealed non-organized electron-dense deposits in the expanded mesangial area and inner aspect of the glomerular basement membranes. In accordance with the histological findings, we diagnosed γ3-HCDD. There was no evidence of plasma cell dyscrasia as a result of bone marrow aspiration. Serum and urine monoclonal proteins were not detected by immunoelectrophoresis and immunofixation electrophoresis. The serum free light chain ratio was within normal range. At first, prednisolone was administrated at a dose of 40 mg/day. However, a therapeutic effect was not observed. Urinary protein was not decreased and renal function further deteriorated. Therefore, melphalan plus prednisolone (MP) therapy was initiated. After 4 courses of MP therapy, the clinical parameters, including proteinuria, serum creatinine, albumin, and complement level (C3 and C4) were ameliorated. To date, the patient has been followed for 28 months, and long-term renal survival has been observed. CONCLUSIONS: In this case, hematologic disease such as multiple myeloma was not detected; however, MP therapy was effective. Recently, the novel concept of monoclonal gammopathy of renal significance (MGRS) has been reported. MIDD, which includes HCDD, is one category of MGRS. In MGRS, aggressive chemotherapy may induce favorable renal outcomes.

Discovery of a gamma heavy chain disease in a patient followed-up for a lymphoplasma cell proliferative disorder.

Gamma-heavy chains disease is a rare disease, with very few cases described in the literature. It is characterized by the presence of a monoclonal gamma-heavy chain without associated light chain. Its prevalence and prognosis are unknown. We report here the accidental discovery of a case of gamma-heavy chain disease during a pancytopenia exploration, performed in the hospital, in a patient known since 2002 for a lymphoplasmacytic type lymphoma first localized in bone marrow.

[A case of light and heavy chain deposition disease].

Monoclonal immunoglobulin deposition disease is rare in medical practice. The light and heavy chain deposition disease is characterized by deposition of monoclonal antibodies in the basement of membrane. Kidney is the most frequently involved organ. There was a male patient diagnosed as light and heavy chain deposition disease in department of Nephrology of the Second Xiangya Hospital, Central South University by renal biopsy. After treatment by oral prednisone, melphalan and thalidomide, the patient's proteinuria and serum creatinine decreased. The retrospective analysis of this case provides a guide for doctors to understand the light and heavy chain deposition disease. Early diagnosis and treatment could improve the prognosis.

IgD heavy-chain deposition disease: detection by laser microdissection and mass spectrometry.

Monoclonal Ig deposition disease (MIDD) is a rare complication of monoclonal gammopathy characterized by deposition of monoclonal Ig light chains and/or heavy chains along the glomerular and tubular basement membranes. Here, we describe a unique case of IgD deposition disease. IgD deposition is difficult to diagnose, because routine immunofluorescence does not detect IgD. A 77-year-old man presented with proteinuria and renal failure, and kidney biopsy analysis showed a nodular sclerosing GN with extensive focal global glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Immunofluorescence was negative for Ig deposits, although electron microscopy showed deposits in the glomeruli and along tubular basement membranes. Laser microdissection of glomeruli and mass spectrometry of extracted peptides showed a large spectra number for IgD, and immunohistochemistry showed intense glomerular and tubular staining for IgD. Together, these findings are consistent with IgD deposition disease. Bone marrow biopsy analysis showed 5% plasma cells, which stained for IgD. The patient was treated with bortezomib and dexamethasone, which resulted in improvement of hematologic parameters but no improvement of renal function. The diagnosis of IgD deposition disease underscores the value of laser microdissection and mass spectrometry in further evaluating renal biopsies when routine assessment fails to reach an accurate diagnosis.

A unique case of γ-heavy chain deposition disease characterized by concomitant deposition of γ2 and γ4 subclasses.

Heavy chain deposition disease (HCDD) is a rare entity. γ-HCDD is the predominant subtype and is characterized by glomerular and tubular deposition of a single γ-heavy chain subclass. To our knowledge, γ-HCDD with simultaneous deposition of two subclasses has not yet been described. A 39-year-old woman presented with hypertension, nephrotic syndrome, anemia, microscopic hematuria and progressive renal dysfunction. A light microscopic examination of renal biopsy specimens showed nodular glomerulosclerosis. Electron microscopy revealed electron-dense deposits along the glomerular and tubular basement membranes. Immunofluorescence microscopy showed positive glomerular and tubular staining for immunoglobulin G (IgG) and negative staining for κ and λ light chains. An analysis of the IgG subclass showed positive staining for both IgG2 and IgG4. We herein describe a unique case of γ-HCDD with concurrent deposition of two subclasses, presenting a new subtype to the disease spectrum.

The heavy chain diseases: clinical and pathologic features.

Heavy chain diseases are a family of rare, systemic syndromes typically associated with or representing a variant of a B-cell neoplasm. Their characteristic feature is production of a mutated immunoglobulin heavy chain incapable of either partnering with light chains in the formation of a full immunoglobulin molecule or of being degraded by the proteasome. The abnormal heavy chain is detected in urine and/or serum without an associated light chain, a pathognomonic finding. Depending on the subtype of the altered heavy chain, these conditions can be subclassified as alpha, gamma, or mu heavy chain disease. We discuss the clinical presentation; epidemiology; laboratory, radiologic, and pathologic features; and treatment options for each of the heavy chain diseases, emphasising the importance of an accurate pathologic diagnosis and correct interpretation of immunologic studies in their identification.