IgD Heavy-Chain Deposition Disease

Abstract

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 77-year-old man of Eastern European descent presented with proteinuria and severe renal insufficiency 6 months ago. The patient had numerous comorbidities, which included chronic obstructive pulmonary disease associated with pulmonary hypertension and bronchiectasis, coronary artery disease, mild aortic stenosis, arterial hypertension, and dyslipidemia.At presentation, the patient complained of fatigue, weight loss, and lower extremity swelling. His BP was normal, and other than the edema, the physical examination was unremarkable. His serum creatinine level was 2.2 mg/dl (194 mmol/L), with an eGFR of 29 ml/min. Additional evaluation showed nephrotic range proteinuria of 5.3 g/d. Microscopic examination of the urine revealed .100 red blood cells per high-power field. Other significant laboratory findings included a mild normocytic anemia with a hemoglobin concentration of 11.4 g/dl and a decreased serum albumin at 2.5 g/dl. Serum calcium level was normal. Serological studies for antinuclear antibody and antineutrophil cytoplasmic antibodies were negative, and complement levels (C3 and C4) were in the normal range.Serum protein electrophoresis showed no M spike on initial evaluation. However, the serum protein immunofixation studies revealed a monoclonal l-band. Serum l-free light-chain level was elevated at 2303 mg/L, with a k:l ratio of 0.02. A 24-hour urine collection revealed the presence of a monoclonal l-light chain. Bone studies did not show any lytic bone lesion.A bone marrow biopsy was performed, and it showed normal cellularity with a mild monoclonal plasmacytosis (5%) and a nega...

The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group

“…LC-MS can also be useful in the diagnosis of MGRSassociated lesions other than immunoglobulin amyloidosis when immunofluorescence studies are not available or have negative findings. An example of the latter situation is IgD heavy-chain deposition disease, which is generally missed by immunofluorescence studies because an IgD antibody is not included in the routine immunofluorescence panel 110 .…”

Characterization of glomerular extracellular matrix by proteomic analysis of laser-captured microdissected glomeruli

“…The combination of LCMD and mass spectrometry identified proteins responsible for glomerular amyloid deposits 18,19 , defined targets of autoantibodies in glomerular immune complexes from membranous nephropathy and lupus nephritis patients 20-22 , identified a patient with IgD heavy-chain disease 23 , and determined the components of the complement cascade in patients with C3 glomerulonephritis 24 .…”

The Complexity and Heterogeneity of Monoclonal Immunoglobulin–Associated Renal Diseases

“…LMD/MS is useful in the setting of patients with unusual cases of MIDD where the MIg is truncated or is not tested for by routine IF studies. For example, HCDD comprising d-heavy chains can be diagnosed using LMD/ MS. 77 4. In some patients with MPGN associated with MIg, in whom the lesions are chronic or the deposits are masked, the MIg may be undetectable by routine IF.…”