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Myelomas

Peripheral Blood Dendritic Cell Subsets from Patients with Monoclonal Gammopathies Show an Abnormal Distribution and Are Functionally Impaired

^aServicio de Citometría & Departamento de Medicina, University of Salamanca, Salamanca, Spain; ^bInstituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer (CSIC-USAL), Salamanca, Spain; ^cService of Hematology, Hospital Clínico de Valladolid, Valladolid, Spain; ^dService of Hematology, Hospital del Bierzo, Ponferrada, Spain; ^eService of Hematology, Hospital Virgen Blanca, León, Spain; ^fService of Hematology, Hospital Virgen del Puerto, Plasencia, Spain; ^gService of Hematology, Hospital Rio Carrión, Palencia, Spain; ^hService of Hematology, Hospital Nstra Sra Sonsoles, Ávila, Spain; ⁱServicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain

Key Words. Circulating dendritic cell subsets • Monoclonal gammopathies • Multiple myeloma • MGUS Plasma cell leukemia

Correspondence: Correspondence: Alberto Orfao, M.D., Ph.D., Servicio de Citometría, Centro de Investigación del Cáncer, Campus Miguel de Unamuno, 37007-Salamanca. Spain. Telephone: 34-923-29-4811; Fax: 34-923-29-4795; e-mail: orfao{at}usal.es

Disclosure: No potential conflicts of interest were reported by the authors, planners, reviewers, or staff managers of this article.

Objectives. The information currently available about dendritic cells (DCs) in patients with different types of monoclonal gammopathy (MG) is limited and frequently controversial. In the present study, we analyzed the ex vivo distribution as well as the phenotypic and functional characteristics of peripheral blood (PB) DCs from different types of MG.

Methods. For this purpose, 61 untreated patients in total with MG were analyzed—MG of undetermined significance (MGUS), 29 cases; multiple myeloma (MM), 28 cases; and plasma cell leukemia (PCL), 4 cases—in comparison with a group of 10 healthy controls.

Results. Our results show an absolute overall higher number of all subsets of PB DCs in PCL, together with lower numbers of myeloid DCs in MM patients. From a phenotypic point of view, PB DC subsets from all types of MG expressed significantly higher levels of HLA molecules and altered patterns of expression of the CD2, CD11c, CD16, CD22, CD62L, and CD86 molecules, in association with altered patterns of secretion of inflammatory cytokines.

Conclusion. In summary, we show the existence of significant abnormalities in the distribution, phenotype, and pattern of secretion of inflammatory cytokines by different subsets of PB DCs from patients with MGs, which could reflect a potentially altered homing of DCs, together with a greater in vivo activation and lower responsiveness of PB DCs, which are already detectable in MGUS patients.