Immunoparesis defined by heavy/light chain pair suppression in smoldering multiple myeloma shows initial isotype specificity and involves other isotypes in advanced disease
Por:
Isola, I, Moreno, DF, Moga, E, Mena, MP, Tovar, N, Rodriguez-Lobato, LG, Oliver-Caldes, A, Salgado, MC, Braso-Maristany, F, Yague, J, Cibeira, MT, Prat, A, Rosinol, L, Blade, J, de Larrea, CF
Publicada:
1 dic 2021
Ahead of Print:
1 ago 2021
Resumen:
Smoldering multiple myeloma (SMM) is an asymptomatic and biologically heterogeneous plasma cell disorder, with a highly variable clinical course. Immunoparesis, defined by total immunoglobulin measurements, has been shown to be an independent risk factor for progression to symptomatic disease. The heavy/light chain (HLC) assay allows precise measurement of the polyclonal immunoglobulin of the same isotype, enabling the evaluation of isotype-matched immunoparesis (IMI). In this study, we prospectively characterized immunoparesis, as determined by HLC measurements, in 53 SMM patients. Severe IMI was present in 51% of patients, while severe IP of uninvolved isotypes (HLC IP) was present in 39%. Most of the patients with severe HLC IP presented with severe IMI, but not the other way around. Isotype specificity of immune suppression was suggested by lower relative values of isotype-matched HLC pairs, both for IgG and IgA SMM. Severe IMI was associated with other risk factors for progression while patients with severe IMI and severe HLC IP showed an even higher risk profile. Both severe IMI and severe IgM HLC IP showed a significantly shorter time to progression. Finally, gene expression analysis demonstrated differences in the bone marrow microenvironment between patients with IMI and IMI plus HLC IP, with an increased expression of genes associated with cytolytic cells. In conclusion, our data supports isotype specificity of early immunoglobulin suppression mechanisms. While suppression of both involved and uninvolved isotypes is associated with risk of progression, the later appears to develop with more advanced disease and could be mediated by different mechanisms.
Filiaciones:
Isola, I:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
Moreno, DF:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
Moga, E:
Univ Autonoma Barcelona, Hosp La Santa Creu & St Pau, Biomed Res Inst St Pau IIB St Pau, Dept Immunol, Barcelona, Spain
Mena, MP:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
Tovar, N:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
Rodriguez-Lobato, LG:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
Oliver-Caldes, A:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
Salgado, MC:
Hosp Clin Barcelona, Dept Biochem, Amyloidosis & Myeloma Unit, Barcelona, Spain
Braso-Maristany, F:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Dept Med Oncol,Translat Genom & Targeted Therapie, Barcelona, Spain
Yague, J:
Hosp Clin Barcelona, Dept Immunol, Amyloidosis & Myeloma Unit, Barcelona, Spain
Cibeira, MT:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
Prat, A:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Dept Med Oncol,Translat Genom & Targeted Therapie, Barcelona, Spain
Rosinol, L:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
Blade, J:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
de Larrea, CF:
Univ Barcelona, Hosp Clin Barcelona, August Pi I Sunyer Biomed Res Inst IDIBAPS, Amyloidosis & Myeloma Unit,Dept Hematol, Barcelona 08036, Spain
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