AL amyloidosis with non-amyloid forming monoclonal immunoglobulin deposition; a case mimicking AHL amyloidosis

Shun Manabe,Michiyasu Hatano,Kosaku Nitta,Michio Nagata,Masahide Yazaki,Fuyuki Kametani,Chihiro Iwasaki

doi:10.1186/s12882-018-1050-y

Abstract

BackgroundImmunoglobulin heavy-and-light-chain amyloidosis (AHL amyloidosis) is a newly established disease entity where both the immunoglobulin heavy-chain and light-chain compose amyloid fibrils. The immunoglobulins responsible for the amyloid fibrils are generally identified by immunostaining and/or laser microdissection-liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS). However, both techniques do not biochemically differentiate immunoglobulins that formed amyloid fibrils from non-responsible immunoglobulins.Case presentationWe herein report a case of 67-year-old female patient with renal amyloidosis due to lymphoplasmacytic lymphoma secreting monoclonal immunoglobulin M (IgM)-kappa. Renal immunostaining monotypically positive for IgM-kappa and LMD-LC-MS/MS identification of mu heavy-chain and kappa light-chain were consistent with the diagnosis of AHL amyloidosis. In order to confirm that both the immunoglobulin heavy-chain and light-chain were forming amyloid fibrils, we performed LC-MS/MS of renal amyloid fibrils isolated by the traditional amyloid purification method. The additional LC-MS/MS identified kappa light-chain only without any heavy-chain component. These results were suggestive that amyloid fibrils were composed by kappa light-chain only and that the mu heavy-chain identified by immunostaining and LMD-LC-MS/MS was derived from the non-specific co-deposition of monoclonal IgM-kappa.ConclusionThe case was AL amyloidosis with non-amyloid forming monoclonal immunoglobulin deposition. While immunostaining and LMD-LC-MS/MS are irreplaceable techniques to classify amyloidosis, confident exclusion of the present condition should be required to diagnose AHL amyloidosis.

Highlights

Immunoglobulin heavy-and-light-chain amyloidosis (AHL amyloidosis) is a newly established disease entity where both the immunoglobulin heavy-chain and light-chain compose amyloid fibrils
In large-scale studies classifying renal amyloidosis by immunostaining and laser microdissection (LMD)-LC-MS/MS [2, 3], the amyloidosis with monotypic immunoglobulin light-chain and heavy-chain deposition were described as AHL amyloidosis
The additional LC-MS/MS only identified immunoglobulin light-chains as the component of amyloid fibrils. This case demonstrated “AL amyloidosis with non-amyloid forming monoclonal immunoglobulin deposition” that might be diagnosed as AHL amyloidosis by immunostaining and LMD-LC-MS/MS

Summary

Conclusion

We demonstrated “AL amyloidosis with non-amyloid forming monoclonal Ig deposition” disguised as AHL amyloidosis. The extraction was solubilised in 10 mM Tris/1 mM EDTA/0.002% Zwittergent buffer and digested overnight with trypsin. The resultant pellet was solubilised in 6 M guanidine/0.5 M Tris-buffered saline, after which it was centrifuged and the supernatant was dialysed against distilled water. Ethics approval and consent to participate This study was granted an exemption from requiring ethics approval from research ethics committee of Yokohama Rosai Hospital because this is a case report on an already described treatment and secondary analysis. Author details 1Kidney and Vascular Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Background

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