Abstract
Background: Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma in virtually every case. However, only a small percentage will progress and at very different rates. In addition, recent data have suggested that MGUS is associated with other comorbidities including infections, suggesting impaired immune function in some MGUS patients. Therefore, we aimed at assessing the value of isotype-matched immunosuppression (IMI; e.g., suppression of an IgAκ in an IgAλ patient), a type of immunosuppression more specific than classical immunoparesis (IP; e.g., IgG and/or IgM suppression in an IgA patient), as a prognostic marker for MGUS progression.
Methods: The Hevylite assay was used to assess IMI and immunoglobulin ratios in 307 serum samples from a cohort of 248 MGUS patients. Follow-up clinical records were available for 154 individuals.
Results: A greater incidence of IMI (51%) over classical IP (37%) was observed, although both show a progressive increase with higher risk groups. Survival analysis of 154 patients showed that severe IMI (>50% suppression) differentiates 2 groups with significantly different time to progression (P = 0.024) while severe IP does not (P = 0.48). Also, a combination of severe IMI and involved monoclonal immunoglobulin >1.5g/dL by Hevylite (both variables found to be independent prognostic markers in multivariate analysis) identified a group of patients with a median time to progression 6-fold shorter than the remaining group (P < 0.0001).
Conclusions: These findings indicate a possible role for IMI in the malignant transformation of MGUS patients and a potential utility as a new risk factor.
Footnotes
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form.
Employment or Leadership: T.M Pais, N.M. Barbosa and M.L. Campos, The Binding Site, Spain. Consultant or Advisory Role: None declared.
Stock Ownership: None declared.
Honoraria: None declared.
Research Funding: None declared.
Expert Testimony: None declared.
Patents: None declared.
Role of Sponsor: The sponsor played a direct role in the preparation and final approval of the manuscript and the choice of enrolled patients.
- Received June 1, 2017.
- Accepted September 5, 2017.
- © 2017 American Association for Clinical Chemistry