Immunoglobulin and free light chain abnormalities in Gaucher disease type I: data from an adult cohort of 63 patients and review of the literature

Abstract

Gaucher disease type I, the most common lysosomal storage disorder, is associated with immunoglobulin abnormalities. We studied the prevalence, risk factors, pathogenesis, and effect of enzyme relation therapy (ERT) on gammopathies in an adult Gaucher disease type I cohort (N = 63) and related the results to a review of the currently available literature. Polyclonal gammopathies and monoclonal gammopathy of undetermined significance (MGUS) in our adult GD I cohort were found in 41% and 19% of patients. These results are similar to the data from the literature and correspond to the increased risk of multiple myeloma (MM) that has been described. The prevalence of MGUS in our cohort increased with age but was not associated with disease severity or exposure time. The serum levels of free light chains of immunoglobulins were measured and were not found predictive for the development of MGUS or MM. Levels of pro- as well as anti-inflammatory cytokines, growth factors, and chemokines, especially those involved in inflammation and B-cell function, are disturbed in GD I, with the most impressive and consisting elevations for interleukin-10 and pulmonary and activation-regulated chemokine. A beneficial effect of ERT on the occurrence and progression of gammopathies was suggested from longitudinal data.

Fig. 1

FLC levels in Gaucher disease type I patients without a monoclonal gammopathy with mild disease (SSI ≤ 8) and severe disease (SSI ≥ 9) (a). FLC levels in Gaucher disease patients with a monoclonal gammopathy and matched Gaucher disease controls (b). MG Monoclonal gammopathy. The normal range for κ was 6.2–30.2 mg/l and for λ was 9.1–40 mg/l. The normal ratio for κ/λ was 0.3–1.57

Fig. 2

Baseline levels of IL-6, IL-10, PARC, and HGF in Gaucher disease patients with a monoclonal gammopathy and matched Gaucher disease controls. Patients with multiple myeloma and/or amyloidosis are marked by an arrow. Dotted lines reflect the upper limit of the normal range. IL Interleukin, HGF hepatocyte growth factor, PARC pulmonary and activation-regulated chemokine, MG monoclonal gammopathy

Fig. 3

Longitudinal changes in plasma levels of immunoglobulin heavy and free light chains, IL-6, IL-10, and PARC. Dotted lines reflect the normal range. Numbers reflect Gaucher disease patients with a monoclonal gammopathy as described in Table 1 (#1–13) and matched Gaucher disease controls (#co1–co13) without a monoclonal gammopathy. IL Interleukin, PARC pulmonary and activation-regulated chemokine

Fig. 4

Bone marrow aspirate showing plasma cells surrounding a Gaucher cell in a patient with Gaucher disease type I and multiple myeloma