Light Chain Variable Region Subgroups of Monoclonal Immunoglobulins in Amyloidosis AL

Abstract

We have reported previously that λ light chains of the VλVI subgroup are preferentially associated with amyloidosis AL(λ) — based on the finding that 5 of 20 λ Bence Jones proteins from such patients were classified serologically and chemically as members of this uncommon V region isotypic subgroup representing ∿10 percent of normal λ chains. Subsequently, using specific anti-λVI antisera, we have identified 6 additional λVI Bence Jones proteins and 1 IgGλVI protein, all of which were obtained from patients with histologically proven amyloidosis. We have determined the complete amino acid sequence of 3 λVI light chains and found that each protein contains a 2-residue V region insertion between positions 68 and 69 — a finding unique to proteins of this λ chain subgroup. The non-λVI chains were classified immunochemically as members of either the λI, λII, λIII, or λIV subgroup. Although monoclonal non-λVI proteins are found in patients with amyloidosis AL(λ), the striking association of a particular V region isotype with amyloidosis AL appears to be limited to λVI proteins. No such association has been evident in patients with amyloidosis AL(κ). Serological analyses with specific anti-κI, anti-κII, anti-κIII, and anti-κIV anti-sera of monoclonal Igκ from 34 such patients revealed that the frequence of distribution of the 4 κ chain V region subgroups approximates that found among non-amyloid associated κ-type proteins. Whether amyloid-associated light chains, especially λVI chains, possess distinct structural features that render them “amyloidogenic” or, alternatively, the light chain degradative process is abnormal in patients with amyloidosis AL remains to be established.