Immunotactoid glomerulopathy: Clinicopathologic and proteomic study

Samih H. Nasr, Mary E. Fidler, Lynn D. Cornell, Nelson Leung, Fernando G Cosio, Salwa S. Sheikh, Abdulrazack A. Amir, Julie A. Vrana, Jason D. Theis, Ahmet Dogan, Sanjeev M Sethi

Research output: Contribution to journalArticle

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Abstract

BackgroundImmunotactoid glomerulopathy (ITG) is a rare glomerular disease. Here, we report the largest clinicopathologic series of ITG and define its proteomic profile.MethodsThe characteristics of 16 ITG patients who were identified from our pathology archives are provided between 1993 and 2011. We also performed laser microdissection and mass spectrometry (LMD/MS) in three cases.ResultsPresentation included proteinuria (100), nephrotic syndrome (69), renal insufficiency (50) and microhematuria (80). Hypocomplementemia was present in 46 and a serum M-spike in 63. Hematologic malignancy was present in 38, including chronic lymphocytic leukemia in 19, lymphoplasmacytic lymphoma in 13 and myeloma in 13. The pattern of glomerular injury was membranoproliferative (56), membranous (31) or proliferative (13) glomerulonephritis. The microtubular deposits were immunoglobulin light chain restricted in 69 and had a mean diameter of 31 nm (range 17-52). During an average of 48 months of follow-up for 12 patients, 50 had remission, 33 had persistent renal dysfunction and 17 progressed to end-stage renal disease. Proteomic analysis by LMD/MS revealed the presence of immunoglobulins, monotypic light chains, complement factors of the classical and terminal pathway and small amount of serum amyloid P-component.ConclusionsHematologic malignancy, particularly lymphoma, is not uncommon in ITG. ITG appears to have a better prognosis than other paraprotein-related renal lesions, with a half of patients expected to recover kidney function with immunosuppressive therapy or chemotherapy. The proteomic profile of ITG is consistent with deposition of monotypic immunoglobulins and activation of the classical and terminal pathway of complement.

Original languageEnglish (US)
Pages (from-to)4137-4146
Number of pages10
JournalNephrology Dialysis Transplantation
Volume27
Issue number11
DOIs
StatePublished - Nov 2012

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Proteomics
Immunoglobulin Light Chains
Microdissection
Kidney
Lymphoma
Mass Spectrometry
Lasers
Serum Amyloid P-Component
Classical Complement Pathway
Paraproteins
Nephrotic Syndrome
Hematologic Neoplasms
B-Cell Chronic Lymphocytic Leukemia
Immunosuppressive Agents
Rare Diseases
Glomerulonephritis
Proteinuria
Chronic Kidney Failure
Renal Insufficiency
Immunoglobulins

Keywords

  • dysproteinemia
  • glomerulonephritis
  • immunotactoid glomerulopathy
  • lymphoma

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Nasr, S. H., Fidler, M. E., Cornell, L. D., Leung, N., Cosio, F. G., Sheikh, S. S., ... Sethi, S. M. (2012). Immunotactoid glomerulopathy: Clinicopathologic and proteomic study. Nephrology Dialysis Transplantation, 27(11), 4137-4146. https://doi.org/10.1093/ndt/gfs348

Immunotactoid glomerulopathy : Clinicopathologic and proteomic study. / Nasr, Samih H.; Fidler, Mary E.; Cornell, Lynn D.; Leung, Nelson; Cosio, Fernando G; Sheikh, Salwa S.; Amir, Abdulrazack A.; Vrana, Julie A.; Theis, Jason D.; Dogan, Ahmet; Sethi, Sanjeev M.

In: Nephrology Dialysis Transplantation, Vol. 27, No. 11, 11.2012, p. 4137-4146.

Research output: Contribution to journalArticle

Nasr, SH, Fidler, ME, Cornell, LD, Leung, N, Cosio, FG, Sheikh, SS, Amir, AA, Vrana, JA, Theis, JD, Dogan, A & Sethi, SM 2012, 'Immunotactoid glomerulopathy: Clinicopathologic and proteomic study', Nephrology Dialysis Transplantation, vol. 27, no. 11, pp. 4137-4146. https://doi.org/10.1093/ndt/gfs348
Nasr SH, Fidler ME, Cornell LD, Leung N, Cosio FG, Sheikh SS et al. Immunotactoid glomerulopathy: Clinicopathologic and proteomic study. Nephrology Dialysis Transplantation. 2012 Nov;27(11):4137-4146. https://doi.org/10.1093/ndt/gfs348
Nasr, Samih H. ; Fidler, Mary E. ; Cornell, Lynn D. ; Leung, Nelson ; Cosio, Fernando G ; Sheikh, Salwa S. ; Amir, Abdulrazack A. ; Vrana, Julie A. ; Theis, Jason D. ; Dogan, Ahmet ; Sethi, Sanjeev M. / Immunotactoid glomerulopathy : Clinicopathologic and proteomic study. In: Nephrology Dialysis Transplantation. 2012 ; Vol. 27, No. 11. pp. 4137-4146.
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abstract = "BackgroundImmunotactoid glomerulopathy (ITG) is a rare glomerular disease. Here, we report the largest clinicopathologic series of ITG and define its proteomic profile.MethodsThe characteristics of 16 ITG patients who were identified from our pathology archives are provided between 1993 and 2011. We also performed laser microdissection and mass spectrometry (LMD/MS) in three cases.ResultsPresentation included proteinuria (100), nephrotic syndrome (69), renal insufficiency (50) and microhematuria (80). Hypocomplementemia was present in 46 and a serum M-spike in 63. Hematologic malignancy was present in 38, including chronic lymphocytic leukemia in 19, lymphoplasmacytic lymphoma in 13 and myeloma in 13. The pattern of glomerular injury was membranoproliferative (56), membranous (31) or proliferative (13) glomerulonephritis. The microtubular deposits were immunoglobulin light chain restricted in 69 and had a mean diameter of 31 nm (range 17-52). During an average of 48 months of follow-up for 12 patients, 50 had remission, 33 had persistent renal dysfunction and 17 progressed to end-stage renal disease. Proteomic analysis by LMD/MS revealed the presence of immunoglobulins, monotypic light chains, complement factors of the classical and terminal pathway and small amount of serum amyloid P-component.ConclusionsHematologic malignancy, particularly lymphoma, is not uncommon in ITG. ITG appears to have a better prognosis than other paraprotein-related renal lesions, with a half of patients expected to recover kidney function with immunosuppressive therapy or chemotherapy. The proteomic profile of ITG is consistent with deposition of monotypic immunoglobulins and activation of the classical and terminal pathway of complement.",
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AU - Cosio, Fernando G

AU - Sheikh, Salwa S.

AU - Amir, Abdulrazack A.

AU - Vrana, Julie A.

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AU - Sethi, Sanjeev M

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N2 - BackgroundImmunotactoid glomerulopathy (ITG) is a rare glomerular disease. Here, we report the largest clinicopathologic series of ITG and define its proteomic profile.MethodsThe characteristics of 16 ITG patients who were identified from our pathology archives are provided between 1993 and 2011. We also performed laser microdissection and mass spectrometry (LMD/MS) in three cases.ResultsPresentation included proteinuria (100), nephrotic syndrome (69), renal insufficiency (50) and microhematuria (80). Hypocomplementemia was present in 46 and a serum M-spike in 63. Hematologic malignancy was present in 38, including chronic lymphocytic leukemia in 19, lymphoplasmacytic lymphoma in 13 and myeloma in 13. The pattern of glomerular injury was membranoproliferative (56), membranous (31) or proliferative (13) glomerulonephritis. The microtubular deposits were immunoglobulin light chain restricted in 69 and had a mean diameter of 31 nm (range 17-52). During an average of 48 months of follow-up for 12 patients, 50 had remission, 33 had persistent renal dysfunction and 17 progressed to end-stage renal disease. Proteomic analysis by LMD/MS revealed the presence of immunoglobulins, monotypic light chains, complement factors of the classical and terminal pathway and small amount of serum amyloid P-component.ConclusionsHematologic malignancy, particularly lymphoma, is not uncommon in ITG. ITG appears to have a better prognosis than other paraprotein-related renal lesions, with a half of patients expected to recover kidney function with immunosuppressive therapy or chemotherapy. The proteomic profile of ITG is consistent with deposition of monotypic immunoglobulins and activation of the classical and terminal pathway of complement.

AB - BackgroundImmunotactoid glomerulopathy (ITG) is a rare glomerular disease. Here, we report the largest clinicopathologic series of ITG and define its proteomic profile.MethodsThe characteristics of 16 ITG patients who were identified from our pathology archives are provided between 1993 and 2011. We also performed laser microdissection and mass spectrometry (LMD/MS) in three cases.ResultsPresentation included proteinuria (100), nephrotic syndrome (69), renal insufficiency (50) and microhematuria (80). Hypocomplementemia was present in 46 and a serum M-spike in 63. Hematologic malignancy was present in 38, including chronic lymphocytic leukemia in 19, lymphoplasmacytic lymphoma in 13 and myeloma in 13. The pattern of glomerular injury was membranoproliferative (56), membranous (31) or proliferative (13) glomerulonephritis. The microtubular deposits were immunoglobulin light chain restricted in 69 and had a mean diameter of 31 nm (range 17-52). During an average of 48 months of follow-up for 12 patients, 50 had remission, 33 had persistent renal dysfunction and 17 progressed to end-stage renal disease. Proteomic analysis by LMD/MS revealed the presence of immunoglobulins, monotypic light chains, complement factors of the classical and terminal pathway and small amount of serum amyloid P-component.ConclusionsHematologic malignancy, particularly lymphoma, is not uncommon in ITG. ITG appears to have a better prognosis than other paraprotein-related renal lesions, with a half of patients expected to recover kidney function with immunosuppressive therapy or chemotherapy. The proteomic profile of ITG is consistent with deposition of monotypic immunoglobulins and activation of the classical and terminal pathway of complement.

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KW - glomerulonephritis

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