Laser Microdissection and Proteomic Analysis of Amyloidosis, Cryoglobulinemic GN, Fibrillary GN, and Immunotactoid Glomerulopathy

Sethi, Sanjeev; Theis, Jason D.; Vrana, Julie A.; Fervenza, Fernando C.; Sethi, Anjali; Qian, Qi; Quint, Patrick; Leung, Nelson; Doğan, Ahmet; Nasr, Samih H.

doi:10.2215/cjn.07030712

Cited by 82 publications

(52 citation statements)

References 14 publications

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“…It is often present in deposits with a fibrillary substructure. 26 In this case as well, a vague fibrillary substructure was noted on electron microscopy. To confirm the LMD/MS findings, we then stained the paraffin-embedded kidney biopsy material for IgD, which showed intense glomerular and tubular basement membrane staining for IgD.…”

Section: Lmd/msmentioning

confidence: 55%

“…24 It has found great use in the diagnosis and typing of amyloidosis, including detection of novel types of amyloidosis. [25][26][27][28][29] Recently, the technique has also been used to determine the composition of deposits in proliferative GN, including immune complex-mediated GN and complement-mediated GN. 2,30,31 Because conventional immunofluorescence microscopy was not helpful, we used LMD/MS to determine the composition of the deposits in our patient, and to our surprise, we found very large spectra numbers for IgD.…”

Section: Lmd/msmentioning

confidence: 99%

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IgD Heavy-Chain Deposition Disease

Royal

Quint²,

Leblanc

et al. 2015

Journal of the American Society of Nephrology

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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...

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Section: Lmd/msmentioning

confidence: 55%

Section: Lmd/msmentioning

confidence: 99%

IgD Heavy-Chain Deposition Disease

Royal

Quint²,

Leblanc

et al. 2015

Journal of the American Society of Nephrology

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“…Im Unterschied zur morphologisch und immunhistologisch sehr ähn-lichen immunotaktoiden GN ist eine Assoziation mit monoklonalen Ablagerungen sehr viel seltener [5,14,20]. Eine vor Kurzem erschienene Arbeit von Sethi und Mitarbeitern [23] untersuchte verschiedene renale Ablagerungserkrankungen (ALAmyloidose, kryoglobulinämische GN, fibrilläre GN, immunotaktoide GN) mittels Lasermikrodissektion und anschließen-der Proteomanalyse und konnte teilweise deutliche Unterschiede in den Spektren verschiedener Strukturproteine zwischen den 4 Erkrankungen zeigen. So wurde z.…”

Section: Fibrilläre Glomerulonephritisunclassified

Seltene renale Ablagerungserkrankungen

Büttner‐Herold

Amann

2015

Nephrologe

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“…However, the important concern is on the limitation of the electron microscope to differentiate the deposits seen in nephropathy. There are many diseases with similar deposits to CN such as amyloidosis and immunotactoid glomerulopathy [4]. The sole use of electron microscope is not enough.…”

mentioning

confidence: 99%

“…The sole use of electron microscope is not enough. It usually requires additional analysis such as immunological test, histological study or proteomic analysis for differential diagnosis [4,5].…”

mentioning

confidence: 99%