Jason D Theis

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (48)303.43 Total impact

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    ABSTRACT: Prognostication and treatment selection for cardiac amyloidosis requires accurate amyloid typing. Study aimed to investigate the utility of histomorphology to predict type. Autopsy cases with cardiac amyloidosis (1998-2010) were typed by mass spectrometry-based proteomics. Deposition patterns were correlated with amyloid type. Among 108 decedents (mean age 75 years; 69% men), 107 had a single type, including ATTR (60 cases), AL (32 λ, 12 κ), AA (2), and AApoAIV (1). Interstitial deposition was more extensive with AL versus ATTR (odds ratio [OR]=6.8, p=0.0004). Histomorphologic patterns of interstitial deposition were mixed in 61% of AL and 61% of ATTR cases, but diffuse pericellular deposits favored AL (OR=10.7, p=0.0001), nodular deposits favored ATTR (OR=3.1, p= 0.0229), and discrete pericellular deposits tended to partially favor ATTR (OR=1.7, p=0.1970). Arterial and venous deposits each favored AL (OR ranging from 9.3 to 192.0, p=0.0022 to <0.0001), and were severe in AL. Endocardial deposits favored AL (OR=46.3, p<0.0001) and were also more severe in AL. Extent and distribution of cardiac amyloidosis strongly correlate with amyloid type, suggesting fundamental differences in the pathobiology of deposition. The tendency for mixed patterns to occur limits the practicality and accuracy of using histopathology for amyloid typing. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Histopathology 07/2015; DOI:10.1111/his.12793 · 3.30 Impact Factor
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    ABSTRACT: Immunoglobulin light chain (LC) amyloidosis (AL) is caused by deposition of clonal LCs produced by an underlying plasma cell neoplasm. The clonotypic LC sequences are unique to each patient and they cannot be reliably detected by either immunoassays or standard proteomic workflows that target the constant regions of LCs. We addressed this issue by developing a novel sequence template-based workflow to detect LC variable (LCV) region peptides directly from AL amyloid deposits. The workflow was implemented in a CAP/CLIA compliant clinical laboratory dedicated to proteomic subtyping of amyloid deposits extracted from either formalin-fixed paraffin-embedded tissues or subcutaneous fat aspirates. We evaluated the performance of the workflow on a validation cohort of 30 AL patients, whose amyloidogenic clone was identified using a novel proteogenomics method, and 30 controls. The recall and negative predictive value of the workflow, when identifying the gene family of the AL clone, was 93% and 98%, respectively. Application of the workflow on a clinical cohort of 500 AL amyloidosis samples highlighted a bias in the LCV gene families used by the AL clones. We also detected similarity between AL clones deposited in multiple organs of systemic AL patients. In summary, AL proteomic data sets are rich in LCV region peptides of potential clinical significance that are recoverable with advanced bioinformatics.
    Journal of Proteome Research 03/2015; 14(4). DOI:10.1021/acs.jproteome.5b00015 · 5.00 Impact Factor
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    ABSTRACT: Amyloidosis is caused by deposition in tissues of abnormal protein in a characteristic fibrillar form. There are many types of amyloidosis, classified according to the soluble protein precursor from which the amyloid fibrils are derived. Accurate identification of amyloid type is critical in every case since therapy for systemic amyloidosis is type specific. In ∼20-25% cases, however, immunohistochemistry (IHC) fails to prove the amyloid type and further tests are required. Laser microdissection and mass spectrometry (LDMS) is a powerful tool for identifying proteins from formalin-fixed paraffin-embedded tissues. We undertook a blinded comparison of IHC, performed at the UK National Amyloidosis Centre, and LDMS, performed at the Mayo Clinic, in 142 consecutive biopsy specimens from 38 different tissue types. There was 100% concordance between positive IHC and LDMS, and the latter increased diagnostic accuracy from 76% to 94%. LDMS in expert hands is a valuable tool for amyloid diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Journal of Clinical Pathology 01/2015; 68(4). DOI:10.1136/jclinpath-2014-202722 · 2.55 Impact Factor
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    ABSTRACT: To determine the impact of amyloid on the prognosis of patients with hypertrophic cardiomyopathy (HC), we reviewed outcomes of patients who underwent septal myectomy for HC from March 7, 1996, to October 9, 2012, with amyloid deposits identified in operative specimens. Amyloid subtypes were differentiated by mass spectrometry-based proteomics. The survival rate was compared with that of an age-matched population (2:1) without amyloid who underwent septal myectomy for HC. Sixteen patients (mean age ± SD 71 ± 8 years; 12 men) met study criteria. All 16 had intraventricular peak systolic gradients reduced intraoperatively from 105 ± 53 mm Hg to 3 ± 7 mm Hg (p <0.001). Amyloid deposits in specimens ranged from minimal to mild. Nine patients had senile (transthyretin-type) amyloidosis, 4 had immunoglobulin-associated amyloidosis, 2 had apolipoprotein A4 amyloidosis type, and 1 had serum amyloid A type. There were no deaths before 30 days. Twelve patients had New York Heart Association class III or IV function preoperatively, and at last follow-up (median 3 years), class I or II. Only 1 patient received postoperative amyloidosis treatment. The postoperative survival rate at 2 and 4 years was 100% (n = 11 at risk) and 91% (n = 6 at risk), respectively, similar to that of the age-matched population with HC without amyloid who underwent myectomy (p = 0.13). Patients undergoing septal myectomy for HC who have histologic evidence of mild amyloidosis have early outcomes and midterm survival similar to those of patients with HC without amyloidosis who undergo myectomy. In conclusion, although longer follow-up is necessary, small amounts of amyloid, regardless of subtype, do not confer a poor prognosis on patients with HC who undergo septal myectomy.
    The American Journal of Cardiology 08/2014; 114(9). DOI:10.1016/j.amjcard.2014.07.058 · 3.43 Impact Factor
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    ABSTRACT: Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. In this study, we describe development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid positive (n=43) and negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We implemented the assay as a clinical test, and analyzed 366 amyloid positive subcutaneous fat aspirates in a 4 year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), lysozyme (1%) were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. Mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for clinical diagnosis and typing of systemic amyloidosis. The assay reveals underlying pathogenesis by identifying variable gene usage in immunoglobulin light chain and the variant peptides in hereditary amyloidosis.
    Haematologica 04/2014; 99(7). DOI:10.3324/haematol.2013.102764 · 5.87 Impact Factor
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    ABSTRACT: Shotgun proteomics of hereditary amyloid deposits generates all the information necessary to identify pathogenic mutant peptides and proteins. However, these mutant peptides are invisible to traditional database search strategies. We developed a two-pronged informatics workflow for detecting both known and novel amyloidogenic mutations from clinical proteomics data sets. We implemented the workflow in a CAP/CLIA certified clinical laboratory dedicated for proteomic subtyping of amyloid deposits extracted from formalin-fixed paraffin-embedded specimens. Performance of the workflow was characterized on a validation cohort of 49 hereditary amyloid samples, with confirmed mutations, and 85 controls. The sensitivity, specificity, positive predictive value and negative predictive value of the known mutation detection workflow were determined to be 92%, 100%, 100% and 96%, respectively. For novel mutation detection workflow, these performance parameters were 82%, 99%, 99%and 90%, respectively. Validated workflow was applied to detect amyloidogenic mutations from a clinical cohort of 150 amyloid samples. The known mutation detection workflow detected rare frame shift mutations in apolipoprotein A1 and fibrinogen alpha amyloid deposits. The novel mutation detection workflow uncovered unanticipated mutations (W22G and C71Y) of the serum amyloid A4 protein present in patient amyloid deposits. In summary, clinical amyloid proteomics data sets contain mutant peptides of clinical significance that are recoverable with improved bioinformatics.
    Journal of Proteome Research 03/2014; 13(5). DOI:10.1021/pr4011475 · 5.00 Impact Factor
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    ABSTRACT: Multiple myeloma is a disease characterized by a clonal expansion of plasma cells that secrete a monoclonal immunoglobulin also referred to as an M-protein. In the clinical laboratory, protein electrophoresis (PEL), immunofixation electrophoresis (IFE), and free light chain nephelometry (FLC) are used to monitor and quantify an M-protein. Here we present an alternative method based on monitoring a clonotypic (i.e. clone specific) peptide from the M-protein heavy chain variable region using LC-MS/MS. Tryptic digests were performed on IgG purified serum from 10 patients with a known IgG M-protein. Digests were analyzed by shot-gun LC-MS/MS and the results were searched against a protein database with the patient specific heavy chain variable region sequence found by gene sequencing added to the database. In all 10 cases, the protein database search matched multiple clonotypic peptides from each patient's heavy chain variable region. The clonotypic peptides were then used to quantitate the amount of M-protein in patient serum samples using selected reaction monitoring (SRM) on a triple quadrupole mass spectrometer. The response for the clonotypic peptide observed by SRM correlated with the response of the M-protein observed by PEL. In addition, the clonotypic peptide was clearly observed by SRM in samples that were negative by IFE and FLC. Monitoring clonotypic peptides using SRM has the capacity to redefine clinical residual disease due to its superior sensitivity and specificity compared to current analytical methods.
    Journal of Proteome Research 02/2014; 13(4). DOI:10.1021/pr5000544 · 5.00 Impact Factor
  • Biophysical Journal 01/2014; 106(2):1a–2a. DOI:10.1016/j.bpj.2013.11.034 · 3.97 Impact Factor
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    ABSTRACT: Amyloidosis derived from leukocyte chemotactic factor 2 (ALECT2) is a recently described disease. Here, we report the characteristics and outcome of 72 patients with renal ALECT2, which included 19 who had another kidney disease on biopsy. Ninety-two percent of patients were Hispanics and over half were elderly. Three had other organ, but not cardiac, amyloidosis involvement. All patients without concurrent disease, except three, presented with chronic renal insufficiency. Proteinuria was variable and absent in a third, whereas nephrotic syndrome and hematuria were rare. After a median follow-up of 26 months, one-third developed end-stage renal disease (ESRD). The median renal survival was 62 months. Independent predictors of renal survival were serum creatinine at diagnosis, with a value of 2.0 mg/dl being the best cutoff for predicting ESRD, percentage global glomerulosclerosis, and presence of diabetes. Only four patients died and four had received chemotherapy for an erroneous diagnosis of immunoglobulin light chain-derived amyloidosis. Five patients underwent kidney transplantation; none had graft loss but one had disease recurrence. Patient survival is superior to renal immunoglobulin light chain-derived amyloidosis and reactive amyloidosis largely due to the absence of cardiac involvement. Thus, renal ALECT2 mainly affects elderly Hispanics who typically present with chronic renal insufficiency and bland urine sediment, with or without proteinuria.Kidney International advance online publication, 22 January 2014; doi:10.1038/ki.2013.558.
    Kidney International 01/2014; 86(2). DOI:10.1038/ki.2013.558 · 8.52 Impact Factor
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    ABSTRACT: Abstract Protein and peptide drugs administered subcutaneously, such as insulin can be amyloidogenic and result in localized amyloid deposits at the sites of medication injections. These iatrogenic amyloidoses typically present as a localized subcutaneous nodule or skin reaction at the site of administration, and often pose diagnostic challenges. We have analyzed the amyloid proteome in 52 cases of insulin and enfuvirtide associated amyloidosis using laser microdissection/tandem mass spectrometry. We show that the deposits are composed of the drug, as well as other amyloid precursor proteins such as apolipoproteins A-I, A-IV, E and serum amyloid protein. Mass spectrometry-based amyloid sub-typing allows for accurate amyloid diagnosis with resultant therapeutic and prognostic implications. This insight into the amyloid proteome in drug-induced amyloidosis may help further understand pathogenesis of amyloid fibril formation.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 01/2014; 21. DOI:10.3109/13506129.2013.876984 · 2.51 Impact Factor
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    ABSTRACT: Using laser microdissection and mass spectrometry-based proteomics (MS) we subtyped amyloid deposits from 130 cases of hepatic amyloidosis. Although we confirmed that immunoglobulin light chain amyloidosis (AL) was the most frequent cause of hepatic amyloidosis, leukocyte cell-derived chemotaxin 2 (LECT2) amyloidosis (ALect2) accounted for 25% of cases. This novel finding was associated with Hispanic ancestry, incidental discovery of amyloid in liver specimens sampled for other unrelated conditions and a characteristic pattern of hepatic amyloid deposition. Although ALect2 patients had a common LECT2 polymorphism, pathogenic mutations were not discovered, suggesting that constitutive or compensatory LECT2 overexpression led to ALect2 deposition. These findings indicate that ALect2 is common cause of hepatic amyloidosis in the United States population, and subtyping hepatic amyloid deposits by an accurate analytic method such as MS is required for optimal clinical management of hepatic amyloidosis patients and to avoid incorrect and unnecessarily toxic therapies.
    Blood 01/2014; 123(10). DOI:10.1182/blood-2013-07-517938 · 10.43 Impact Factor
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    ABSTRACT: Individuals heterozygous for the V122I mutation in transthyretin (TTR) tend to develop cardiac amyloidosis, often after the seventh decade of life. Although homozygotes have been reported, these have typically been single case reports. We report a cohort of 13 V122I homozygotes. TTR gene sequencing results from the Mayo Clinic Molecular Genetics Laboratory between September 2004 and January 2013 were reviewed; 177 heterozygotes and 13 homozygotes for the V122I alteration were identified. Detailed clinical history was available for the 24 heterozygotes seen at Mayo Clinic. We compared age at onset of disease for this group to homozygotes, both alone and pooled with the 11 homozygotes from the literature. Individuals with homozygous V122I manifested symptoms a mean of 10 years earlier than heterozygotes (63.8 ± 5.7 versus 72 ± 8.1 yrs, P = 0.0002). Further, males were significantly overrepresented in both heterozygous and homozygous individuals. There was a trend for an even higher male bias in the homozygous group. All 24 homozygotes were African American, whereas four of the heterozygotes were reported as white. Two novel V122I compound heterozygotes were also identified, with clinical presentation in the late fifth or early sixth decade of life. This study is the largest homozygous V122I cohort reported and demonstrates association with earlier age at onset. It also highlights the uncertain penetrance, particularly with respect to sex.
    The Journal of molecular diagnostics: JMD 10/2013; 16(1). DOI:10.1016/j.jmoldx.2013.08.001 · 3.96 Impact Factor
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    ABSTRACT: Monoclonal gammopathy is increasingly recognized as a common cause of membranoproliferative glomerulonephritis (MPGN); however, establishing this diagnosis can be challenging. We report the case of a 58-year-old asymptomatic woman who presented with proteinuria with protein excretion of 5,000mg/d, microscopic hematuria, and normal kidney function. Kidney biopsy was consistent with MPGN pattern of injury. Immunofluorescence studies were positive for nonspecific segmental immunoglobulin M (IgM) and C3 staining. Electron microscopy showed subendothelial, subepithelial, and mesangial electron-dense deposits. The workup excluded an infectious or autoimmune disease, but IgG κ monoclonal protein was detected in serum at a concentration of 0.4mg/dL. Because there was a mismatch between the serum monoclonal protein (IgG κ) and immunofluorescence staining pattern (nonspecific IgM, no light chain restriction), laser microdissection and mass spectrometry were performed on the kidney biopsy tissue. This identified the deposits as monoclonal IgG κ, thereby leading to the diagnosis of monoclonal gammopathy-associated MPGN. Our case emphasizes the importance of searching for an underlying cause of MPGN, reviews the technique of laser microdissection-mass spectrometry, and highlights its application as a pathology tool for the evaluation of monoclonal gammopathy-related glomerulonephritis.
    American Journal of Kidney Diseases 10/2013; 63(2). DOI:10.1053/j.ajkd.2013.09.007 · 5.76 Impact Factor
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    ABSTRACT: The field of proteomics has long promised to deliver tools that positively impact patient care and clinical outcomes. Shotgun proteomics, in particular, with its capability for characterizing thousands of proteins in complex clinical samples has been a leading tool in the search for biomarkers and proteomic-based diagnostic tests. In the Special Feature, Jason Theis and co-workers at Mayo Clinic in Rochester, MN provide a first-hand perspective of challenges encountered to develop and implement a shotgun proteomics-based diagnostic assay for sub-typing forms of amyloidoisis. Using shotgun proteomics to identify amyloid proteins from microdissected biopsy tissue the diagnostic is able to characterize more than 20 subtypes of amyloidosis. Developing the assay is only one step to clinical acceptance and the authors and discuss how they have been able to make this key transition.
    Journal of Mass Spectrometry 10/2013; 48(10):i. DOI:10.1002/jms.3193 · 2.71 Impact Factor
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    ABSTRACT: Shotgun proteomics technology has matured in the research laboratories and is poised to enter clinical laboratories. However, the road to this transition is sprinkled with major technical unknowns such as long-term stability of the platform, reproducibility of the technology and clinical utility over traditional antibody-based platforms. Further, regulatory bodies that oversee the clinical laboratory operations are unfamiliar with this new technology. As a result, diagnostic laboratories have avoided using shotgun proteomics for routine diagnostics. In this perspectives article, we describe the clinical implementation of a shotgun proteomics assay for amyloid subtyping, with a special emphasis on standardizing the platform for better quality control and earning clinical acceptance. This assay is the first shotgun proteomics assay to receive regulatory approval for patient diagnosis. The blueprint of this assay can be utilized to develop novel proteomics assays for detecting numerous other disease pathologies. Copyright © 2013 John Wiley & Sons, Ltd.
    Journal of Mass Spectrometry 10/2013; 48(10):1067-1077. DOI:10.1002/jms.3264 · 2.71 Impact Factor
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    ABSTRACT: Amyloidosis affecting lymph nodes (LN) may occur in the setting of systemic amyloidosis or as an entity localized to the site of production (peritumoral). Why some LN amyloid remains peritumoral is unknown. We speculated that the composition of amyloid in these two presentations differs. We analyzed the amyloid proteome in LN amyloid samples to identify differences between the systemic and peritumoral subtypes. In immunoglobulin-derived LN amyloidosis (N=26), 70% had heavy chain amyloid (AH or mixed AH/AL). True localized lymph node amyloidosis was rare, with only 2 patients without a monoclonal protein component. Nineteen patients (73%) had typical amyloid syndromes (100% of AL vs 67% of AH/AL, p 0.02). A trend to improved survival for the AH/AL group in comparison to AL (median 5-year survival 48 vs 19 months, p 0.06) was seen. Mass spectrometric amyloid analysis is a powerful tool for characterizing amyloid and may provide additional prognostic information.
    American Journal of Hematology 07/2013; 88(7). DOI:10.1002/ajh.23456 · 3.48 Impact Factor
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    ABSTRACT: Background and objectivesThe kidney is the organ most commonly involved in systemic amyloidosis. This study reports the largest clinicopathologic series of renal amyloidosis.Design, setting, participants, & measurementsThis study provides characteristics of 474 renal amyloidosis cases evaluated at the Mayo Clinic Renal Pathology Laboratory from 2007 to 2011, including age, sex, serum creatinine, proteinuria, type of amyloid, and tissue distribution according to type.ResultsThe type of amyloid was Ig amyloidosis in 407 patients (85.9%), AA amyloidosis in 33 (7.0%), leukocyte chemotactic factor 2 amyloidosis in 13 (2.7%), fibrinogen A chain amyloidosis in 6 (1.3%), Apo AI, Apo AII, or Apo AIV amyloidosis in 3 (0.6%), combined AA amyloidosis/Ig heavy and light chain amyloidosis in 1 (0.2%), and unclassified in 11 (2.3%). Laser microdissection/mass spectrometry, performed in 147 cases, was needed to determine the origin of amyloid in 74 of the 474 cases (16%), whereas immunofluorescence failed to diagnose 28 of 384 light chain amyloidosis cases (7.3%). Leukocyte chemotactic factor 2 amyloidosis and Apo AI, Apo AII, or Apo AIV amyloidosis were characterized by diffuse interstitial deposition, whereas fibrinogen A chain amyloidosis showed obliterative glomerular involvement. Compared with other types, Ig amyloidosis was associated with lower serum creatinine, higher degree of proteinuria, and amyloid spicules.Conclusions In the authors' experience, the vast majority of renal amyloidosis cases are Ig derived. The newly identified leukocyte chemotactic factor 2 amyloidosis form was the most common of the rarer causes of renal amyloidosis. With the advent of laser microdissection/mass spectrometry for amyloid typing, the origin of renal amyloidosis can be determined in >97% of cases.
    Clinical Journal of the American Society of Nephrology 05/2013; 8(9). DOI:10.2215/CJN.10491012 · 5.25 Impact Factor
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    ABSTRACT: We report a 12-year-old boy with nephrotic syndrome due to renal AA amyloidosis. The AA amyloidosis was associated with a 3-year history of systemic-onset juvenile idiopathic arthritis. The presence of serum amyloid A protein was confirmed by laser microdissection of Congo Red-positive glomeruli and vessels followed by liquid chromatography and tandem mass spectrometry; this analysis excluded hereditary and familial amyloidosis. Aggressive management of the systemic-onset juvenile idiopathic arthritis resulted in improvement in clinical and laboratory parameters. The case represents an unusual cause of nephrotic syndrome in children. Early diagnosis of renal amyloidosis and management of systemic-onset juvenile idiopathic arthritis is paramount to preventing progression of kidney disease.
    American Journal of Kidney Diseases 05/2013; 62(4). DOI:10.1053/j.ajkd.2013.02.377 · 5.76 Impact Factor
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    ABSTRACT: PURPOSE OF REVIEW: Laser microdissection (LMD) and mass spectrometry (MS) is a new technique that consists of dissection of glomeruli, tryptic digestion of dissected material, analysis by MS and generation of a protein profile using different algorithms. The review focuses on the use of this methodology as an ancillary technique in a clinical laboratory for the diagnosis of kidney diseases. RECENT FINDINGS: LMD/MS is used in the diagnosis and typing of kidney diseases with organized deposits such as amyloidosis. Uncommon and familial forms of renal amyloidosis are diagnosed and typed on the basis of the presence of specific amyloidogenic proteins. LMD/MS is used to confirm and identify immunoglobulins and complement factors in immune complex mediated and complement-mediated proliferative glomerulonephritis, respectively. In particular, LMD/MS can detect monoclonal immunoglobulins in cases of equivocal immunofluorescence studies in monoclonal immunoglobulins-associated glomerulonephritis. LMD/MS can detect specific complement factors of the alternative pathway and terminal pathway in complement-mediated glomerulonephritis. SUMMARY: LMD/MS is currently used for diagnosis and typing of amyloidosis. In addition, LMD/MS is useful in determining the type of immunoglobulins and complement factors in immune complex and complement-mediated glomerulonephritis, respectively.
    Current opinion in nephrology and hypertension 03/2013; 22(3). DOI:10.1097/MNH.0b013e32835fe37c · 3.96 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVES: Organized deposits are present in amyloidosis, fibrillary GN, and immunotactoid glomerulopathy. However, the constituents of the deposits are not known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Laser microdissection of glomeruli followed by mass spectrometry was performed to determine the composition of the deposits. The results were compared with cryoglobulinemic GN. RESULTS: The results are divided into four major groups: amyloidogenic proteins, structural/other proteins, complement proteins, and Igs. With regards to amyloidogenic proteins, large spectra numbers of apolipoprotein E are noted in amyloidosis (41.8±20.9) compared with fibrillary (15.6±12.5) and immunotactoid (12.3±12) glomerulopathy. Apolipoprotein E was absent in cryoglobulinemic GN. Serum amyloid P component is present in large spectra numbers in amyloidosis (14.1±6.7) and small spectra numbers in immunotactoid glomerulopathy, but it is absent in fibrillary and cryoglobulinemic GN. However, large spectra numbers of Ig γ-1 chain C region are present in immunotactoid glomerulopathy (47.3±34.6) compared with fibrillary (16.25±19.7) and cryoglobulinemic (13.3±4.9) GN. All cases of Ig light chain-associated amyloidosis showed spectra for the respective Ig light-chain C region (mean=10±1.7). CONCLUSIONS: Based on the spectra numbers, the study shows that the relative amount of apolipoprotein E to Ig light-chain C region/amyloidogenic proteins or Ig γ-1 chain C region is associated with the organization of the deposits in amyloidosis, fibrillary GN, and immunotactoid glomerulopathy. However, the absence of apolipoprotein E correlates with the lack of fibrillar deposits in cryoglobulinemic GN.
    Clinical Journal of the American Society of Nephrology 02/2013; 8(6). DOI:10.2215/CJN.07030712 · 5.25 Impact Factor