Restrictive usage of monoclonal immunoglobulin λ light chain germline in POEMS syndrome

Abstract

POEMS syndrome is a rare plasma cell disorder characterized by peripheral neuropathy, monoclonal gammopathy, and high levels of serum vascular endothelial growth factor, the pathogenesis of which remains unclear. A unique feature of this syndrome is that the proliferating monoclonal plasma cells are essentially -restricted.

Characterization of immunoglobulin λ light chain variable region (IGLV) gene and its relationship with clinical features in patients with POEMS syndrome

“…Our result is consistent with the finding from the previous three studies [4][5][6]. Combining results from all four studies, there are 57 cases to demonstrate that IGLV gene was strictly derived from either IGLV 1-40 or IGLV 1-44 gene in POEMS syndrome.…”

“…For example, Soubrier et al first reported that two POEMS patients had M protein derived from the IGLV 1-40 gene [4]. Abe et al found that IGLV genes were restricted to two genes in 11 patients-nine patients had IGLV 1-44 and two patients had IGLV 1-40 [5]. Dispenzieri et al also reported that IGLV genes were either IGLV 1-40 or IGLV 1-44 in 14 patients [6].…”

“…Although it is well known that M protein is essentially λ light chain, its role in the pathogenesis of POEMS syndrome is not yet fully understood. To date, three studies have reported that the immunoglobulin λ light chain variable region (IGLV) genes in patients with POEMS syndrome are highly restricted usage of limited two genes, which are IGLV1-40 and IGLV1-44 [4][5][6]. For example, Soubrier et al first reported that two POEMS patients had M protein derived from the IGLV 1-40 gene [4].…”

The repertoire of λ light chains causing predominant amyloid heart involvement and identification of a preferentially involved germline gene, IGLV1-44

“…1,2,27 Mutations are clearly relevant for destabilization of the LC molecule, a critical aspect related to amyloidogenicity. 1,2,27 In this view, it will be of interest to compare amyloid-forming IGVL1-44 LC with LC from POEMS syndrome, 28 a rare nonamyloid plasma cell disorder that is characterized by significant overuse of IGVL1-44 sequences, 29 to identify possible disease-related structural features. Unlike IGVL3-1 and IGVL6-57, IGVL1-44 is then clearly not exclusively associated with amyloidosis.…”

POEMS Syndrome: An Atypical Presentation

“…Table 1 -IMWG criteria for PEOMS syndrome Elevated VEGF levels in patients with POEMS syndrome is important as it is implicated in the pathogenesis of the syndrome itself 4 but we hadn't estimated its level in our patient because the development of polyneuropathy in POEMS syndrome is thought to be VEGF related. The presence of monoclonal plasma cell disorder is almost always present in POEMS and predominantly lambda type of light chain as seen in our patient 5 . It is known that the M Band on protein electrophoresis is usually seen in the Gamma region but patient showed the M band spike in the Beta-1 regions which is less common.…”