title: Gamma-delta T lymphocytes and 25-hydroxy vitamin D levels as key factors in autoimmunity and inflammation: the case of zoledronic acid-induced acute phase reaction.
abstract: Zoledronic acid (ZA) infusion for osteoporosis is frequently associated with the onset of an acute phase reaction (APR) secondary to the activation of γδ T cell receptor (TCR) lymphocytes (γδ T cells) and to low vitamin D levels, similar to what is observed in chronic inflammation and autoimmunity. In this study we investigated whether the phenotype of γδ T cells is associated with APR and 25-OH vitamin D (25-OHvD) levels. For flow-cytometry analysis, peripheral blood samples were obtained from 52 osteoporotic women prior to 5 mg ZA intravenous infusion and from nine women (five with APR) one week later. Twenty-six/52 (50%) patients reported APR and APR+ cases had a higher percentage of central memory Th1-like γδ T cells. One week after ZA infusion, APR was associated with a decreased percentage of central memory Th1-like γδ T cells, an increase in the percentage and activation of effector memory Th1-like γδ T cells, and an increase in Th17-like γδ T cells. Lower 25-OHvD levels were significantly associated with APR, but no correlation was found between 25-OHvD level and γδ T cell percentage or subsets. In conclusion, patients experiencing APR related to ZA infusion have lower 25-OHvD levels and we suggest that the higher percentage of central memory Th1-like γδ T cells and the expansion of effector memory Th1-like and Th17-like γδ T cells are associated with the occurrence of APR.
authors: Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy BIOMETRA Department, University of Milan, Italy carlo.selmi@unimi.it.
authors: M
authors: M
authors: De Santis
authors: Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy BIOMETRA Department, University of Milan, Italy.
authors: F
authors: F
authors: Cavaciocchi
authors: Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy BIOMETRA Department, University of Milan, Italy.
authors: A
authors: A
authors: Ceribelli
authors: Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy.
authors: C
authors: C
authors: Crotti
authors: Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy.
authors: E
authors: E
authors: Generali
authors: Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy.
authors: G
authors: G
authors: Fabbriciani
authors: Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy Division of Rheumatology, Allergy, and Clinical Immunology, University of California, USA carlo.selmi@unimi.it.
authors: C
authors: C
authors: Selmi
authors: Rheumatology and Clinical Immunology, Humanitas Research Hospital, Rozzano, Italy.
authors: M
authors: M
authors: Massarotti
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced* / Q000276:immunology; D000368:Aged; D000369:Aged, 80 and over; D015551:Autoimmunity; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014807:Vitamin D; D000077211:Zoledronic Acid; C104450:25-hydroxyvitamin D
keywords: Osteoporosis; adverse event; bisphosphonate; bone loss; zoledronate