Prevalence of Monoclonal Gammopathy in Patients With Primary Hyperparathyroidism

Arnulf, Bertrand; Bengoufa, Djaouïda; Sarfati, E.; Toubert, Marie‐Elisabeth; Meignin, Véronique; Brouet, Jean‐Claude; Fermand, Jean‐Paul

doi:10.1001/archinte.162.4.464

Cited by 49 publications

(48 citation statements)

References 26 publications

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“…24 Hyperproduction of the parathyroid hormone, which results in high IL-6 production in the BM, might also favor the emergence of a PC proliferation. 25 Alternatively, instead of being involved in the early step of the MM emergence, IL-6 overproduction by MSCs might result from transforming effect of the myeloma cells that would persist in remission favoring the occurrence of a subsequent relapse. In order to solve these issues, longitudinal studies of patients at different steps of their disease course are ongoing.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma

et al. 2006

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Section: Discussionmentioning

confidence: 99%

Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma

et al. 2006

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“…Evaluation of T reg cells at various stages in MGUS may provide further insight into the development and progression of MGUS to MM. Additionally, MM is reported to be associated with a number of autoimmune disorders, such as thyroid abnormalities, 27 rheumatoid arthritis, 28 and renal complications. 29 It will be intriguing to study whether these conditions are the cause or the effect of dysfunctional T reg cells in MM.…”

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confidence: 99%

Dysfunctional T regulatory cells in multiple myeloma

Prabhala

Neri

Bae

et al. 2006

Blood

217

172

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IntroductionT regulatory (T reg ) cells play an important role in the maintenance of self-tolerance, control of auto-immunity, and regulation of T-cell homeostasis, and they modulate overall immune responses against infectious agents and tumor cells. 1 Natural T reg cells develop during normal T-cell maturation in the thymus and represent 5% to 10% of the CD4 ϩ cell compartment in the peripheral blood. 2 These cells express CD4 and CD25 surface antigens as well as CTLA-4, GITR, CD103, CD62L, CD69, CD134, CD71, CD54, and CD45RA. 3 The suppressive activity of T reg cells is associated with the overexpression of FOXP3, a member of the forkhead/winged helix family, which acts as a transcriptional repressor. 4 T reg cells suppress CD25 Ϫ CD4 ϩ T-cell proliferation on the basis of cell-cell contact and suppress immune responses by secreting immunosuppressive cytokines such as IL-10 and TGF-␤. 5 A significant impairment of T-cell function is observed in patients with multiple myeloma (MM) and patients with monoclonal gammopathy of undetermined significance (MGUS). Although phenotypic and functional aberrations in CD4 and CD8 cells have been described in MM and MGUS, 6-9 the biologic basis for these abnormalities remains unclear. Because T reg cells play an important role in modulating normal immune responses, the abnormal T reg -cell activity in myeloma patients could contribute to immune dysfunction in MM and could provide a new target to enhance immune responses. Therefore, in this study we evaluated natural T reg -cell number and function in patients with MGUS and MM and compared them with those of healthy donors. Study design Phenotypic characterizationCD4 ϩ CD25 ϩ T reg -cell numbers were analyzed by flow cytometric analyses in peripheral-blood mononuclear cells (PBMCs) collected from healthy donors, patients with MGUS, and patients with newly diagnosed MM. Approval for these studies was obtained from the institutional review board of the Dana-Farber Cancer Institute and the Veterans Administration (VA) Boston Healthcare System. Informed consent was provided according to the Declaration of Helsinki. Measurement of FOXP3 expressionAs FOXP3 is specifically expressed by T reg cells and is required for their suppressive activity, we analyzed the proportion of PBMCs expressing intracellular FOXP3 using anti-FOXP3 antibody (eBiosciences, San Diego, CA) using dual-color flow cytometry and multiphoton microscopy. Level of protein expression was quantitated by Western blotting and by real-time reverse transcription-polymerase chain reaction (RT-PCR) using previously described methods. 10 Suppressive activity of T regulatory cellsTo evaluate the function of T reg cells, PBMCs were first depleted of CD25 ϩ T cells (which contain T reg cells) by positive selection using anti-CD25-coated microbeads (Miltenyi Biotech, Auburn, CA), according to the manufacturer's instructions. 11 PBMCs depleted of CD25 ϩ cells and control PBMCs containing CD25 ϩ cells were stimulated with anti-CD3 antibody for 3 days, and proliferation was measu...

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“…5 Alguns trabalhos sugerem que a frequência de hiperparatireoidismo primário (HP) está aumentada em neoplasias, ampliando o espectro da etiologia da hipercalcemia nesses pacientes. 4 Apesar de rara, a associação de hiperparatireoidismo primário e gamopatia monoclonal não é excepcional e, apesar de ainda não esclarecida, acredita-se que esta associação se deva ao fato de que a imunoglobulina monoclonal pode atuar como um fator de crescimento para as células da paratireoide, de forma semelhante ao que acontece na estimulação de células da tireoide por imunoglobulina G na doença de Basedow Graves. 6,7 Por outro lado, alguns autores sugerem que o aumento do paratormônio sérico estimula células osteoblásticas estromais a secretarem interleucina 6 (IL6) e essa interleucina seria responsável pelo desenvolvimento de células plasmáticas clonais.…”

Section: Discussionunclassified

“…3 O HP parece ter frequência aumentada em neoplasias tanto benignas quanto malignas. 4 Assim, a associação de HP e GMSI deve ser lembrada em casos de hipercalcemia. Devido à raridade dessa associação, apresenta-se aqui um relato de caso de paciente da Enfermaria de Clínica Médica do Hospital Universitário Lauro Wanderley -Universidade Federal da Paraíba.…”

Section: Introductionunclassified

Unknown significance monoclonal gammopathy (USMG) and primary hyperparathyroidism (PH) on diferential diagnosis of hypercalcemia - Case Report

Alexandre¹,

Beltrão²,

Filho³

et al. 2012

Jornal Brasileiro De Nefrologia

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Prevalence of Monoclonal Gammopathy in Patients With Primary Hyperparathyroidism

Cited by 49 publications

References 26 publications

Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma

Phenotypic and functional characterization of bone marrow mesenchymal stem cells derived from patients with multiple myeloma

Dysfunctional T regulatory cells in multiple myeloma

Unknown significance monoclonal gammopathy (USMG) and primary hyperparathyroidism (PH) on diferential diagnosis of hypercalcemia - Case Report

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