The sensitivity and specificity of the routine kidney biopsy immunofluorescence panel are inferior to diagnosing renal immunoglobulin-derived amyloidosis by mass spectrometry

Maria L. Gonzalez Suarez, Pingchuan Zhang, Samih H. Nasr, Insara Jaffer Sathick, Wonngarm Kittanamongkolchai, Paul J. Kurtin, Mariam P Alexander, Lynn D. Cornell, Mary E. Fidler, Joseph Peter Grande, Loren P. Herrera Hernandez, Samar M. Said, Sanjeev M Sethi, Angela Dispenzieri, Morie Gertz, Nelson Leung

Research output: Contribution to journalArticle

Abstract

Immunoglobulin light chain amyloidosis is the most frequent type of renal amyloidosis in the United States, accounting for 81% of cases. Accurate typing is crucial for early diagnosis and treatment of immunoglobulin-derived amyloidosis and to avoid treating other amyloidoses with potentially toxic chemotherapy. Immunofluorescence is the first step to type renal immunoglobulin-derived amyloidosis but the performance characteristics of this method are largely unknown. Here, we establish the sensitivity and specificity of immunofluorescence for diagnosing immunoglobulin-derived amyloidosis in patients whose amyloid typing was performed by the current gold standard of laser microdissection/mass spectrometry. Renal biopsy pathology reports originating from several institutions with a diagnosis of amyloidosis and which had amyloid typing by laser microdissection/mass spectrometry performed at our center were reviewed. Reported immunofluorescence staining for kappa or lambda of 2+ or more, with weak or no staining for the other light chain was considered positive for light chain amyloidosis by immunofluorescence. Based on microdissection/mass spectrometry results, of the 170 cases reviewed, 104 cases were typed as immunoglobulin-derived amyloidosis and 66 were typed as non-immunoglobulin-derived amyloidosis. Immunofluorescence sensitivity for diagnosing immunoglobulin-derived amyloidosis was 84.6%. The remaining 16 cases could not be diagnosed by immunofluorescence due to reported weak staining for all antigens or reported lack of preferential staining for one antigen. Immunofluorescence specificity was 92.4%. Five cases, all amyloid A amyloidosis, were misdiagnosed as immunoglobulin-derived amyloidosis by immunofluorescence. Immunofluorescence failed to accurately differentiate immunoglobulin-derived from non-immunoglobulin-derived amyloidosis in 12.3% of cases of renal amyloidosis. Relying on immunofluorescence alone for determining immunoglobulin-derived vs. non-immunoglobulin-derived amyloidosis may lead to misdiagnosis. Thus, immunofluorescence has inferior sensitivity and specificity compared with laser microdissection/mass spectrometry in the typing of immunoglobulin-derived amyloidosis.

Original languageEnglish (US)
JournalKidney international
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Amyloidosis
Fluorescent Antibody Technique
Immunoglobulins
Mass Spectrometry
Kidney
Biopsy
Sensitivity and Specificity
Microdissection
Amyloid
Staining and Labeling
Lasers
Diagnostic Errors
Immunoglobulin Light Chains
Light
Antigens
Poisons

Keywords

  • immunofluorescence
  • mass spectrometry
  • renal amyloidosis

ASJC Scopus subject areas

  • Nephrology

Cite this

The sensitivity and specificity of the routine kidney biopsy immunofluorescence panel are inferior to diagnosing renal immunoglobulin-derived amyloidosis by mass spectrometry. / Gonzalez Suarez, Maria L.; Zhang, Pingchuan; Nasr, Samih H.; Sathick, Insara Jaffer; Kittanamongkolchai, Wonngarm; Kurtin, Paul J.; Alexander, Mariam P; Cornell, Lynn D.; Fidler, Mary E.; Grande, Joseph Peter; Herrera Hernandez, Loren P.; Said, Samar M.; Sethi, Sanjeev M; Dispenzieri, Angela; Gertz, Morie; Leung, Nelson.

In: Kidney international, 01.01.2019.

Research output: Contribution to journalArticle

Gonzalez Suarez, Maria L. ; Zhang, Pingchuan ; Nasr, Samih H. ; Sathick, Insara Jaffer ; Kittanamongkolchai, Wonngarm ; Kurtin, Paul J. ; Alexander, Mariam P ; Cornell, Lynn D. ; Fidler, Mary E. ; Grande, Joseph Peter ; Herrera Hernandez, Loren P. ; Said, Samar M. ; Sethi, Sanjeev M ; Dispenzieri, Angela ; Gertz, Morie ; Leung, Nelson. / The sensitivity and specificity of the routine kidney biopsy immunofluorescence panel are inferior to diagnosing renal immunoglobulin-derived amyloidosis by mass spectrometry. In: Kidney international. 2019.
@article{87dfe2b2317a4176a06d17e04da193c8,
title = "The sensitivity and specificity of the routine kidney biopsy immunofluorescence panel are inferior to diagnosing renal immunoglobulin-derived amyloidosis by mass spectrometry",
abstract = "Immunoglobulin light chain amyloidosis is the most frequent type of renal amyloidosis in the United States, accounting for 81{\%} of cases. Accurate typing is crucial for early diagnosis and treatment of immunoglobulin-derived amyloidosis and to avoid treating other amyloidoses with potentially toxic chemotherapy. Immunofluorescence is the first step to type renal immunoglobulin-derived amyloidosis but the performance characteristics of this method are largely unknown. Here, we establish the sensitivity and specificity of immunofluorescence for diagnosing immunoglobulin-derived amyloidosis in patients whose amyloid typing was performed by the current gold standard of laser microdissection/mass spectrometry. Renal biopsy pathology reports originating from several institutions with a diagnosis of amyloidosis and which had amyloid typing by laser microdissection/mass spectrometry performed at our center were reviewed. Reported immunofluorescence staining for kappa or lambda of 2+ or more, with weak or no staining for the other light chain was considered positive for light chain amyloidosis by immunofluorescence. Based on microdissection/mass spectrometry results, of the 170 cases reviewed, 104 cases were typed as immunoglobulin-derived amyloidosis and 66 were typed as non-immunoglobulin-derived amyloidosis. Immunofluorescence sensitivity for diagnosing immunoglobulin-derived amyloidosis was 84.6{\%}. The remaining 16 cases could not be diagnosed by immunofluorescence due to reported weak staining for all antigens or reported lack of preferential staining for one antigen. Immunofluorescence specificity was 92.4{\%}. Five cases, all amyloid A amyloidosis, were misdiagnosed as immunoglobulin-derived amyloidosis by immunofluorescence. Immunofluorescence failed to accurately differentiate immunoglobulin-derived from non-immunoglobulin-derived amyloidosis in 12.3{\%} of cases of renal amyloidosis. Relying on immunofluorescence alone for determining immunoglobulin-derived vs. non-immunoglobulin-derived amyloidosis may lead to misdiagnosis. Thus, immunofluorescence has inferior sensitivity and specificity compared with laser microdissection/mass spectrometry in the typing of immunoglobulin-derived amyloidosis.",
keywords = "immunofluorescence, mass spectrometry, renal amyloidosis",
author = "{Gonzalez Suarez}, {Maria L.} and Pingchuan Zhang and Nasr, {Samih H.} and Sathick, {Insara Jaffer} and Wonngarm Kittanamongkolchai and Kurtin, {Paul J.} and Alexander, {Mariam P} and Cornell, {Lynn D.} and Fidler, {Mary E.} and Grande, {Joseph Peter} and {Herrera Hernandez}, {Loren P.} and Said, {Samar M.} and Sethi, {Sanjeev M} and Angela Dispenzieri and Morie Gertz and Nelson Leung",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.kint.2019.05.027",
language = "English (US)",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - The sensitivity and specificity of the routine kidney biopsy immunofluorescence panel are inferior to diagnosing renal immunoglobulin-derived amyloidosis by mass spectrometry

AU - Gonzalez Suarez, Maria L.

AU - Zhang, Pingchuan

AU - Nasr, Samih H.

AU - Sathick, Insara Jaffer

AU - Kittanamongkolchai, Wonngarm

AU - Kurtin, Paul J.

AU - Alexander, Mariam P

AU - Cornell, Lynn D.

AU - Fidler, Mary E.

AU - Grande, Joseph Peter

AU - Herrera Hernandez, Loren P.

AU - Said, Samar M.

AU - Sethi, Sanjeev M

AU - Dispenzieri, Angela

AU - Gertz, Morie

AU - Leung, Nelson

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Immunoglobulin light chain amyloidosis is the most frequent type of renal amyloidosis in the United States, accounting for 81% of cases. Accurate typing is crucial for early diagnosis and treatment of immunoglobulin-derived amyloidosis and to avoid treating other amyloidoses with potentially toxic chemotherapy. Immunofluorescence is the first step to type renal immunoglobulin-derived amyloidosis but the performance characteristics of this method are largely unknown. Here, we establish the sensitivity and specificity of immunofluorescence for diagnosing immunoglobulin-derived amyloidosis in patients whose amyloid typing was performed by the current gold standard of laser microdissection/mass spectrometry. Renal biopsy pathology reports originating from several institutions with a diagnosis of amyloidosis and which had amyloid typing by laser microdissection/mass spectrometry performed at our center were reviewed. Reported immunofluorescence staining for kappa or lambda of 2+ or more, with weak or no staining for the other light chain was considered positive for light chain amyloidosis by immunofluorescence. Based on microdissection/mass spectrometry results, of the 170 cases reviewed, 104 cases were typed as immunoglobulin-derived amyloidosis and 66 were typed as non-immunoglobulin-derived amyloidosis. Immunofluorescence sensitivity for diagnosing immunoglobulin-derived amyloidosis was 84.6%. The remaining 16 cases could not be diagnosed by immunofluorescence due to reported weak staining for all antigens or reported lack of preferential staining for one antigen. Immunofluorescence specificity was 92.4%. Five cases, all amyloid A amyloidosis, were misdiagnosed as immunoglobulin-derived amyloidosis by immunofluorescence. Immunofluorescence failed to accurately differentiate immunoglobulin-derived from non-immunoglobulin-derived amyloidosis in 12.3% of cases of renal amyloidosis. Relying on immunofluorescence alone for determining immunoglobulin-derived vs. non-immunoglobulin-derived amyloidosis may lead to misdiagnosis. Thus, immunofluorescence has inferior sensitivity and specificity compared with laser microdissection/mass spectrometry in the typing of immunoglobulin-derived amyloidosis.

AB - Immunoglobulin light chain amyloidosis is the most frequent type of renal amyloidosis in the United States, accounting for 81% of cases. Accurate typing is crucial for early diagnosis and treatment of immunoglobulin-derived amyloidosis and to avoid treating other amyloidoses with potentially toxic chemotherapy. Immunofluorescence is the first step to type renal immunoglobulin-derived amyloidosis but the performance characteristics of this method are largely unknown. Here, we establish the sensitivity and specificity of immunofluorescence for diagnosing immunoglobulin-derived amyloidosis in patients whose amyloid typing was performed by the current gold standard of laser microdissection/mass spectrometry. Renal biopsy pathology reports originating from several institutions with a diagnosis of amyloidosis and which had amyloid typing by laser microdissection/mass spectrometry performed at our center were reviewed. Reported immunofluorescence staining for kappa or lambda of 2+ or more, with weak or no staining for the other light chain was considered positive for light chain amyloidosis by immunofluorescence. Based on microdissection/mass spectrometry results, of the 170 cases reviewed, 104 cases were typed as immunoglobulin-derived amyloidosis and 66 were typed as non-immunoglobulin-derived amyloidosis. Immunofluorescence sensitivity for diagnosing immunoglobulin-derived amyloidosis was 84.6%. The remaining 16 cases could not be diagnosed by immunofluorescence due to reported weak staining for all antigens or reported lack of preferential staining for one antigen. Immunofluorescence specificity was 92.4%. Five cases, all amyloid A amyloidosis, were misdiagnosed as immunoglobulin-derived amyloidosis by immunofluorescence. Immunofluorescence failed to accurately differentiate immunoglobulin-derived from non-immunoglobulin-derived amyloidosis in 12.3% of cases of renal amyloidosis. Relying on immunofluorescence alone for determining immunoglobulin-derived vs. non-immunoglobulin-derived amyloidosis may lead to misdiagnosis. Thus, immunofluorescence has inferior sensitivity and specificity compared with laser microdissection/mass spectrometry in the typing of immunoglobulin-derived amyloidosis.

KW - immunofluorescence

KW - mass spectrometry

KW - renal amyloidosis

UR - http://www.scopus.com/inward/record.url?scp=85070883089&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070883089&partnerID=8YFLogxK

U2 - 10.1016/j.kint.2019.05.027

DO - 10.1016/j.kint.2019.05.027

M3 - Article

JO - Kidney International

JF - Kidney International

SN - 0085-2538

ER -