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Blood, 1 August 2001, Vol. 98, No. 3, pp. 714-720
IMMUNOBIOLOGY
The tropism of organ involvement in primary systemic
amyloidosis: contributions of Ig VL germ line
gene use and clonal plasma cell burden
Raymond L. Comenzo,
Yana Zhang,
Carmen Martinez,
Keren Osman, and
Guillermo A. Herrera
From the Division of Hematologic Oncology, Department
of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; the
Hospital Clinic of Barcelona, Catalonia, Spain; and the Department of
Pathology, Medicine and Cell Biology and Anatomy, Louisiana State
University Health Sciences Center, Shreveport.
Primary systemic amyloidosis (AL) is a protein conformation
disorder in which monoclonal immunoglobulin light chains produced by
clonal plasma cells are deposited as amyloid in the kidneys, heart,
liver, or other organs. Why patients with AL present with amyloid
disease that displays such organ tropism is unknown. This study tested
the hypothesis that both the light-chain variable region (Ig
VL) germ line genes used by AL clones and the
plasma cell burden influenced AL organ tropism. To assess the renal
tropism of some light chains, an in vitro renal mesangial cell model of amyloid formation was used. With reverse transcription-polymerase chain
reaction, Ig VL genes were sequenced from 60 AL
patients whose dominant involved organs were renal (52%), cardiac
(25%), hepatic (8%), peripheral nervous system (8%), and soft tissue and other (7%). Patients with clones derived from the 6a
V VI germ line gene were more likely to
present with dominant renal involvement, whereas those with clones
derived from the 1c, 2a2, and 3r
V genes were more likely to present with
dominant cardiac and multisystem disease. Patients with
V clones were more likely to have dominant
hepatic involvement and patients who met the Durie criteria for myeloma
(38%, 23 of 60) were more likely to present with dominant cardiac
involvement independent of germ line gene use. In the in vitro model,
unlike all other AL light chains tested,  VI light chains formed
amyloid rapidly both with and without amyloid-enhancing factor. These
data support the hypothesis that germ line gene use and plasma cell
burden influence the organ tropism of AL.
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