Background: Axial spondyloarthritis (AxSpA) is a chronic rheumatic disease characterized by spine inflammation, abnormal bone growth, and paradoxically osteoporosis and vertebral fractures. The pathogenesis of skeletal deficits in this disease is poorly understood.
Purpose: We sought to evaluate volumetric bone mineral density (vBMD) and bone microarchitecture in patients with AxSpA and to identify disease-related factors associated with skeletal abnormalities.
Purpose Of Review: Osteoporosis in axial spondyloarthritis may be modified by therapy. The purpose of this systematic review is to describe (i) the effect of TNFi on BMD, (ii) the effect of secukinumab on BMD, and (iii) the effect of secukinumab on radiographic disease progression in axSpA.
Recent Findings: We searched PubMed, Embase, and Cochrane using the following retrieval languages: spondyloarthritis, ankylosing spondylitis, TNF, IL-17, x-rays, and osteoporosis.
Semin Arthritis Rheum
April 2017
Objective: Gout patient self-management knowledge and adherence to treatment regimens are poor. Our objective was to assess the feasibility and acceptability of a multidisciplinary team-based pilot program for the education and monitoring of gout patients.
Methods: Subjects completed a gout self-management knowledge exam, along with gout flare history and compliance questionnaires, at enrollment and at 6 and 12 months.
Objective: To examine the ability of mature dendritic cells (DCs) or macrophages intentionally exposed to lipopolysaccharide or apoptotic or necrotic cells to break tolerance in normal mice.
Methods: We adoptively transferred into C57BL/6 mice a variety of syngeneic myeloid antigen-presenting cell populations exposed to different activation stimuli as well as to meals of necrotic and apoptotic cells. We studied expression of autoimmunity in the immunized mice by serologic evaluation of autoantibody production, subclass analysis of Ig production, clinical evidence of kidney disease, glomerular immune complex deposition, and renal pathology.
T cell-specific adaptor protein (TSAd) is a T lineage-restricted signaling adaptor molecule that is thought to participate in the assembly of intracellular signaling complexes in T cells. Previous studies of TSAd-deficient mice have revealed a role for TSAd in the induction of T cell interleukin 2 secretion and proliferation. We now show that TSAd-deficient mice are susceptible to lupus-like autoimmune disease.
View Article and Find Full Text PDFImmunoregulation of lymphocytes and macrophages in the peripheral immune system is achieved in part by activation-induced cell death. Members of the TNF receptor family including Fas (CD95) are involved in the regulation of activation-induced cell death. To determine whether activation-induced cell death plays a role in regulation of dendritic cells (DCs), we examined interactions between Ag-presenting murine DCs and Ag-specific Th1 CD4+ T cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 1995
The Fas/APO-1 cytotoxic pathway plays an important role in the regulation of peripheral immunity. Recent evidence indicates that this regulatory function operates through deletion of activated T and B lymphocytes by CD4+ T cells expressing the Fas ligand. Because macrophages play a key role in peripheral immunity, we asked whether Fas was involved in T-cell-macrophage interactions.
View Article and Find Full Text PDFMice defective in Fas-mediated apoptosis (lpr phenotype) have an intrinsic B cell abnormality that predisposes them to autoantibody production. To investigate potential roles for the Fas receptor (FasR) in B cell tolerance, FasR expression and function were evaluated at different stages of B cell development. FasR expression was very low or absent on pro- and pre-B cells, but was detected in early B cell lines and was up-regulated following IFN-gamma-induced maturation of the pre-B cell line 70-Z.
View Article and Find Full Text PDFWe have investigated the phenotypic and functional characteristics of murine pre-B cells obtained in semisolid and liquid culture with stem cell factor (SCF) and interleukin 7 (IL-7). Both serum-supplemented and serum-deprived culture conditions were used. The source of bone marrow cells was either normal mice (CD1 and C3H) or the lupus strain of mice MRL/lpr and its congenic strain MRL/+.
View Article and Find Full Text PDFThe ability of SCID mice to accept xenografts has been exploited to study the survival, function and potential of peripheral blood mononuclear cells (PBMC) from patients with autoimmune disorders to produce tissue injury in the mouse. Studies performed with PBMC obtained from patients with organ specific and multisystem autoimmune diseases indicate that human PBMC survive in SCID mice for several months, produce IgG and autoantibodies with the same specificities as are found in the donor. Tissue injury is not generally observed in the SCID mouse recipient.
View Article and Find Full Text PDFPeripheral blood mononuclear cells (PBMC) injected into severe combined immune deficiency (SCID) mice continue to secrete human immunoglobulin and respond to immunization with recall antigens. PBMC for patients with autoimmune diseases produce autoantibodies of the same specificities but at lower levels compared to the donor. SCID recipients of patients' PBMC fail to develop clinical disease although some histological lesions suggestive of autoimmunity have been reported.
View Article and Find Full Text PDFMRL/lpr (lpr) mice spontaneously develop a lupus-like illness as well as massive lymphadenopathy. Attempts to transfer autoimmunity by adoptive transfer or radiation bone marrow chimeras have been unsuccessful. Since severe combined immunodeficiency (SCID) mice have been engrafted with human and rat xenografts without apparent graft-versus-host disease (GVHD), we subjected SCID mice to low-dose irradiation and reconstituted the mice with spleen cells from young or old lpr mice or with lpr bone marrow.
View Article and Find Full Text PDFMice with SCID disease have previously been successfully engrafted with human peripheral blood mononuclear cells (PBMC) obtained from normal individuals and from patients with various diseases. To determine whether SCID mice engrafted with SLE PBMC produced autoantibodies with specificities similar to those in the SLE donor, and to investigate which variables influence autoantibody production in the SCID recipients, we injected PBMC from 16 SLE patients into SCID mice and tested the recipients for autoantibodies to DNA and to five recombinant autoantigens. Ten out of 16 (68%) lupus and six out of nine (67%) normal grafts were successful as determined by the presence of human IgG greater than or equal to 5 micrograms/ml of SCID serum post-transfer.
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