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Clonal immunoglobulin light chain variable region germline gene use in AL amyloidosis: association with dominant amyloid‐related organ involvement and survival after stem cell transplantation
Author(s) -
Comenzo Raymond L.,
Wally Jeremy,
Kica Geraldina,
Murray Jessica,
Ericsson Thomas,
Skinner Martha,
Zhang Yana
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01591.x
Subject(s) - immunoglobulin light chain , germline , al amyloidosis , transplantation , biology , tropism , amyloidosis , clone (java method) , antibody , immunology , pathology , gene , genetics , medicine , virus
AL (primary or immunoglobulin light chain) amyloidosis (AL) differs from myeloma per se in that tissue deposits of amyloid are found, typically in association with small numbers of clonal plasma cells producing λ light chains, and also in that AL patients typically present with a predominantly dysfunctional organ‐system. This constellation of features — fibrillar deposits comprised of light chains, λ light chain predominance, and organ‐system tropism and dysfunction — remains unexplained. Select patients with AL respond to haemopoietic stem cell transplantation (SCT) with clinical improvement and extended survival, particularly those who do not have cardiac involvement. In order to ascertain whether the organ‐system tropism of AL was associated with immunoglublin light chain variable region (Ig V L ) germline gene utilization, we attempted to clone, sequence and assign germline donors to the clonal Ig V L genes of 62 AL patients, all of whom were treated with SCT. We succeeded in 39 cases, identifying clonal AL genes derived from donors of the λI ( n = 10), λII ( n = 5), λIII ( n = 6), λVI ( n = 11) and KI ( n = 7) subtypes. The majority of the donors ( IGLV6S1, DPL5, DPL2, DPL23 and LFVK431 ) were genes that appear in the expressed repertoire <5% of the time, suggesting an intrinsic propensity to form amyloid under certain conditions. Patients whose clones derived from the λVI IGLV6S1 donor uniformly presented with dominant renal involvement while those with other V λ or unknown donors often had dominant cardiac or other organ involvement, particularly patients whose clones derived from the λI DPL2 donor. In addition, both early (<3 months) and overall post‐SCT survival were significantly better in λVI IGLV6S1 patients compared to patients with other V λ donors. These findings indicate that there are important associations in AL amyloidosis among Ig V L gene utilization, organ‐system tropism and post‐SCT survival.