Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: Macrophage harbingers of disease severity
Teresa Greenwell-Wild
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland
Ms Greenwell-Wild and Dr. N. M. Moutsopoulos contributed equally to this work.
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
Search for more papers by this authorNiki M. Moutsopoulos
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland
Ms Greenwell-Wild and Dr. N. M. Moutsopoulos contributed equally to this work.
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
Search for more papers by this authorMaria Gliozzi
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland
Search for more papers by this authorEfstathia Kapsogeorgou
National University of Athens Medical School, Athens, Greece
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
Search for more papers by this authorZoila Rangel
Center for Information Technology, NIH, Bethesda, Maryland
Search for more papers by this authorPeter J. Munson
Center for Information Technology, NIH, Bethesda, Maryland
Search for more papers by this authorHaralampos M. Moutsopoulos
National University of Athens Medical School, Athens, Greece
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
Search for more papers by this authorCorresponding Author
Sharon M. Wahl
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
National Institute of Dental and Craniofacial Research/NIH, Oral Infection and Immunity Branch, Building 30, Room 320, 30 Convent Drive, MSC 4352, Bethesda, MD 20892Search for more papers by this authorTeresa Greenwell-Wild
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland
Ms Greenwell-Wild and Dr. N. M. Moutsopoulos contributed equally to this work.
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
Search for more papers by this authorNiki M. Moutsopoulos
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland
Ms Greenwell-Wild and Dr. N. M. Moutsopoulos contributed equally to this work.
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
Search for more papers by this authorMaria Gliozzi
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland
Search for more papers by this authorEfstathia Kapsogeorgou
National University of Athens Medical School, Athens, Greece
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
Search for more papers by this authorZoila Rangel
Center for Information Technology, NIH, Bethesda, Maryland
Search for more papers by this authorPeter J. Munson
Center for Information Technology, NIH, Bethesda, Maryland
Search for more papers by this authorHaralampos M. Moutsopoulos
National University of Athens Medical School, Athens, Greece
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
Search for more papers by this authorCorresponding Author
Sharon M. Wahl
National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland
Ms Greenwell-Wild and Drs. N. M. Moutsoploulos, Kapsogeorgou, H. M. Moutsopoulos, and Wahl have submitted a provisional application to patent the use of highly conserved chitinase-like glycoproteins CHI3L1/YKL-40 and CHIT1 as Sjögren's syndrome diagnostics.
National Institute of Dental and Craniofacial Research/NIH, Oral Infection and Immunity Branch, Building 30, Room 320, 30 Convent Drive, MSC 4352, Bethesda, MD 20892Search for more papers by this authorMs Greenwell-Wild and Dr. N. M. Moutsopoulos contributed equally to this work.
Abstract
Objective
Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology that targets salivary and lacrimal glands and may be accompanied by multiorgan systemic manifestations. To further the understanding of immunopathology associated with SS and identify potential therapeutic targets, we undertook the present study comparing the gene expression profiles of salivary glands with severe inflammation versus those of salivary glands with mild or no disease.
Methods
Using microarray profiling of salivary gland tissue from patients with SS and control subjects, we identified target genes, which were further characterized in tissue, serum, and cultured cell populations by real-time polymerase chain reaction and protein analysis.
Results
Among the most highly expressed SS genes were those associated with myeloid cells, including members of the mammalian chitinase family, which had not previously been shown to be associated with exocrinopathies. Both chitinase 3–like protein 1 and chitinase 1, highly conserved chitinase-like glycoproteins (one with enzymatic activity and one lacking enzymatic activity), were evident at the transcriptome level and were detected within inflamed tissue. Chitinases were expressed during monocyte-to-macrophage differentiation and their levels augmented by stimulation with cytokines, including interferon-α (IFNα).
Conclusion
Because elevated expression of these and other macrophage-derived molecules corresponded with more severe SS, the present observations suggest that macrophages have potential immunopathologic involvement in SS and that the tissue macrophage transcription profile reflects multiple genes induced by IFNα.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
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