ALH Amyloidosis: An Underrecognized Diagnostic Entity
L Kim, S Meehan, A Chang. University of Chicago, Chicago, IL
Background: In the renal biopsy workup of AL amyloidosis, variable IgG immunofluorescence (IF) staining of the amyloid deposits can be seen. We conducted the following study to determine the significance of this observation.
Design: Our pathology archives were reviewed from 2005 to 2008 and renal biopsies of AL (n=24) and AH (n=1) amyloidosis were identified of which were 11 biopsies had at least 1+ staining for IgG (DAKO). Direct IF microscopy using FITC-conjugated antibodies to IgG1, IgG2, IgG3, and IgG4 (Binding Site, San Diego, CA) was performed. The slides were scored semi-quantitatively from 0-4+.
IF staining resultsAbbreviations: SPEP - serum protein electrophoresis; N/A - not available
|1||2-3+||lambda 3-4+||0||0||0||0||IgG lambda|
|3||3+||lambda 3+||0||0||0||0||IgG lambda|
|4||trace-1+||kappa 1-2+||0||0||0||0||IgG kappa|
|5||1-2+||lambda 3+||0||0||0||0||lambda only|
|7||trace-1+||kappa 2+||0||0||0||0||IgG kappa|
Electron microscopy confirmed the presence of amyloid fibrils in all cases and did not show evidence of monoclonal immunoglobulin deposition disease. When the intensity of IgG IF staining of amyloid deposits was stronger than albumin but less than the corresponding monoclonal light chain, the absence of IgG isotype staining was interpreted as a non-specific finding. Two patients had circulating IgG lambda paraproteins with strong (3+) IF staining for both IgG and lambda light chains but no staining for IgG1, IgG2, IgG3, or IgG4. Overall, 20 biopsies (80%) of AL (15 lambda, 5 kappa light chain), 4 (16%) ALH, and 1 (4%) AH amyloidosis cases were identified.
Conclusions: Similar to light and heavy chain deposition disease, ALH amyloidosis is an appropriate term for amyloid deposits consisting of both a monoclonal heavy and light chain component. This diagnostic subtype of amyloidosis may be underrecognized. Additional antibodies to IgG1, IgG2, IgG3, and IgG4 should be studied to determine if discrepant IF staining results between pan-IgG and the IgG isotypes in select amyloidosis cases could be due to significant mutation of the heavy chain component, conformational change of the amyloidogenic heavy chain, stearic hindrance, or trapping of non-amyloidogenic heavy chains.
Category: Kidney (does not include tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 246, Wednesday Afternoon