title: Disappearance of immunoglobulins from persistent renal amyloid deposits following stem cell transplantation for heavy-and light-chain amyloidosis.
abstract: BACKGROUND
  Immunoglobulin (Ig)-related amyloidosis is the most common type of systemic amyloidosis in the developed countries and involves the kidney in most cases. Clinical remission can be achieved with chemotherapy and/or autologous stem cell transplantation (ASCT). Previous case reports have showed persistence of renal amyloid mass in light-chain amyloidosis (AL) even in the setting of hematologic and renal response.
  
  
  METHODS
  We report a novel finding in two cases of heavy- and light-chain amyloidosis (AHL) in which monoclonal Ig but not serum amyloid P (SAP), apolipoprotein E (ApoE) or amyloid bulk in the kidney regressed after successful therapy.
  
  
  RESULTS
  In the pre-treatment renal biopsies, the amyloid deposits stained for one heavy and one light chains (IgG + λ in one case and IgA + κ in one case). Laser microdissection followed by mass spectrometry (LMD/MS) in both cases showed abundant spectra for Ig heavy and light chains, SAP and ApoE. Both patients achieved a hematologic response with disappearance of the monoclonal protein from serum and urine and normalization of serum-free light chain ratio, but renal response occurred in only one patient. Repeat kidney biopsies showed persistence of fibrillar amyloid deposits, but regression of Ig from the amyloid deposits based on immunofluorescence. LMD/MS on the repeat biopsy performed in one case also showed disappearance of Ig but not SAP or ApoE.
  
  
  CONCLUSIONS
  Our finding suggests that effective chemotherapy and/or ASCT in some patients with AHL not only eliminates the circulating pathogenic monoclonal Ig but also the Ig component of amyloid deposits, which may translate into renal response. This, however, may not lead to regression of amyloid deposits themselves. The latter may require more time or addition of therapeutic agents that target amyloid-associated proteins such as SAP, which are not commercially available.
authors: Divisions of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors: Sami
authors: S
authors: Safadi
authors: Divisions of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors: Ahmed
authors: A
authors: Saad
authors: Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors: Patrick S
authors: PS
authors: Quint
authors: Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors: Sanjeev
authors: S
authors: Sethi
authors: Divisions of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA Hematology, Mayo Clinic, Rochester, MN, USA.
authors: Nelson
authors: N
authors: Leung
authors: Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors: Paul
authors: P
authors: Kurtin
authors: Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
authors: Samih H
authors: SH
authors: Nasr
mesh_terms: D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D061346:Laser Capture Microdissection; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation
chemical_list: D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains
keywords: amyloid; laser microdissection; renal biopsy; stem cell transplant