Abstract
Monoclonal gammopathies (MG) constitute a spectrum of disorders starting from a monoclonal gammopathy of undetermined significance (MGUS) to active disease requiring therapy such as multiple myeloma. MG are characterized by proliferation of clonal plasma cells (PC) secreting a monoclonal protein either as intact immunoglobulin or free kappa or lambda free light chains (FLC). We hypothesized that a polyclonal elevation of serum FLC may indicate an inflammatory state that precedes development of MG. We studied 15,630 individuals from Olmsted county, who did not have MGUS based on baseline screening studies. At a median follow-up of 18.1 years, 264 patients had developed a clonal PC disorder; 252 with MGUS, 1 with SMM, 8 with MM, and 3 with amyloidosis, translating to an annual incidence of development of a MG of 0.1%. We examined the baseline polyclonal ΣFLC (kappa + lambda FLC) from the initial screening and grouped them into deciles. The highest decile group had a 2.6-fold (95% CI; 1.8, 3.7) increase in the risk of developing a MG, P < 0.001. We demonstrate for the first time, the increased risk of developing MG in patients with elevated serum FLC, suggesting that an underlying inflammatory state may play an etiologic role.
Highlights
Monoclonal gammopathy of undetermined significance (MGUS) is a relatively common abnormality in the older individuals, characterized by clonal proliferation of mature plasma cells in the bone marrow, with small numbers of these cells observed in the peripheral blood.[1]
We examined if increased polyclonal ΣFLC levels in the highest decile were associated with an increase in the risk of MGUS and related disorders including smoldering multiple myeloma (SMM), MM, and immunoglobulin light chain amyloidosis compared with patients in the lower 9 deciles
Much has been learned in terms of the risk factors for progression from MGUS to smoldering multiple myeloma and active multiple myeloma
Summary
Monoclonal gammopathy of undetermined significance (MGUS) is a relatively common abnormality in the older individuals, characterized by clonal proliferation of mature plasma cells in the bone marrow, with small numbers of these cells observed in the peripheral blood.[1]. Large epidemiological studies of MGUS from various parts of the globe have estimated this risk to be ~1% per year, with no change in risk over the years. While much has been studied regarding the risk of progression from MGUS, there is limited information regarding the risk factors for development of MGUS.[7] There are clearly genetic and environmental factors that predisposes one to the development of monoclonal gammopathies. Increased risk of MGUS have been found among the first degree relatives of those with a diagnosis of myeloma, and genetic loci have been identified that are associated with an increased risk of development of myeloma.[8] Environmental factors such as exposure to ionizing radiation, petroleum products, and pesticides
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