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Saposin C is a frequent target of paraproteins in Gaucher disease‐associated MGUS/multiple myeloma

Patients with Gaucher disease (GD) have an increased risk of monoclonal gammopathies for which antigenic targets might play a role in their pathogenesis. Here we report the identification of saposin C (sapC) as high‐titre (1:1 000 000) target structure of 7/16 GD‐associated paraproteins. Anti‐sapC immunoglobulin (Ig) showed identity with the paraprotein Ig type and subclass in each patient that showed anti‐sapC immunoreactivity. Absorption and depletion studies completely removed the paraprotein from the sera of GD patients. No immunoreactivity against sapC was detected in healthy donors and in other plasma cell dyscrasias, demonstrating that anti‐sapC reactivity is highly restricted to GD. Several uncharacterized forms of post‐translational modified sapC were detected but their role in the pathogenesis is not clear. We confirm the frequent presence of low‐titre (1:250) anti‐lysolipid reactivities in the sera of GD patients but we could show that this immunoreactivity is not mediated by the paraprotein and is not restricted to GD patients.