Figure 2. Lipid Reactivity of Immunoglobulin in Sporadic Gammopathy.
Panel A shows the results of SPEP analysis, LGL1-specific blotting, and control blotting (with the use of human albumin as the control antigen) on serum specimens obtained from patients with monoclonal gammopathy, showing lipid reactivity or no lipid reactivity, and from healthy controls. Panel B shows the results of lysophosphatidylcholine (LPC)–specific blotting, which was performed on serum specimens obtained from the same patients and healthy controls. Panel C shows the results of SPEP analysis, followed by LGL1, cardiolipin, lipid A, and diacylglycerol (DAG)–specific blotting on purified immunoglobulin obtained from patients with monoclonal gammopathy without Gaucher’s disease (sporadic monoclonal gammopathy), patients with Gaucher’s disease– associated monoclonal gammopathy, and healthy controls. Panel D shows the ligand-dependent enrichment of clonal immunoglobulin. Serum specimens obtained from three patients with lipid-reactive monoclonal gammopathy and three patients with lipid-nonreactive monoclonal gammopathy were incubated with control (C) or sphingosine (S)–coated sepharose beads; the bead-binding fraction was analyzed for the presence of clonal immunoglobulin by Western blot. The bottom panels show densitometric quantitation of bands performed with the use of ImageJ software. Panel E shows the ligand-dependent depletion of clonal immunoglobulin. Serum specimens from three patients with lipid-reactive monoclonal gammopathy and three patients with lipid-nonreactive monoclonal gammopathy were incubated with control or sphingosine-coated sepharose beads. The flow-through fraction was analyzed for M-spike depletion by means of SPEP. The bottom panels show densitometric quantitation of bands performed with the use of ImageJ software. The bar graph in Panel F shows the percent reduction in anti-LGL1 antibodies in serum specimens obtained from GBA1−/− mice after treatment with eligulstat (test diet), as compared with mice that received the control diet. Data are means; T bars indicate standard errors. The bar graph in Panel G shows the percent reduction in the M-spike intensity in serum specimens obtained from GBA1−/− mice after treatment with the test diet, as compared with mice that received the control diet. Data are means; T bars indicate standard errors.