acid-phosphatase and Lupus-Erythematosus--Systemic

Type I interferon (IFN-I) is strongly implicated in the pathogenesis of systemic lupus erythematosus (SLE). Here, we focus on new developments in pathways of IFN-I stimulation, the role of IFN-I in syndromes associated with lupus-like diseases, the utility of IFN-I signatures as biomarkers, and the progress of therapeutic agents targeting IFN-I pathways in SLE.. Immune complexesimmune complex are a dominant driver of IFN-I production by activating toll-like receptors (TLRs) in plasmacytoid dendritic cells (pDC) in SLE. The level of IFN-I production is attenuated by C1q in immune complexes and enhanced by natural killer (NK) cells as well as by activated platelets that express CD40L. In addition to immune complexs, cell-intrinsic activation pathways utilize recently described non-TLR RNA and DNA sensors. Some modules or clusters of IFN-I stimulated genes or proteins correlate with disease activity, whereas IFN-I biomarkers of disease flare or specific clinical manifestations need further study. IFN-I blocking studies have reached phase II clinical trials.. Significant progress has been made in defining both TLR as well as non-TLR mediated stimulation of IFN-I. This has helped elucidate the mechanisms of several mutations and common genetic variations in predisposing to SLE. Challenges remain in the establishing the utility of biomarkers and the role of IFN-I blockade in the clinical management of patients with this disease.

Topics: Acid Phosphatase; Antigen-Antibody Complex; Biomarkers; Blood Platelets; Complement C1q; Exodeoxyribonucleases; Humans; Immunity, Innate; Interferon Type I; Isoenzymes; Killer Cells, Natural; Lupus Erythematosus, Systemic; Neutrophils; Phosphoproteins; Signal Transduction; Tartrate-Resistant Acid Phosphatase; Toll-Like Receptors

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Antibodies, Antinuclear; Antigen-Antibody Reactions; Antigens, Neoplasm; Antigens, Viral; Arthus Reaction; Catalase; Catechol Oxidase; Chorionic Gonadotropin; Cytochrome c Group; Enzymes; Epitopes; Glucose Oxidase; Gonadotropins, Pituitary; Histocytochemistry; Humans; Immunity, Cellular; Immunochemistry; Immunoglobulin Fragments; Lupus Erythematosus, Systemic; Peroxidases; Proinsulin

We studied ten individuals from eight families showing features consistent with the immuno-osseous dysplasia spondyloenchondrodysplasia. Of particular note was the diverse spectrum of autoimmune phenotypes observed in these individuals (cases), including systemic lupus erythematosus, Sjögren's syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud's disease and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13, and linkage analysis yielded a combined multipoint log(10) odds (LOD) score of 3.6. Sequencing of ACP5, encoding tartrate-resistant acid phosphatase, identified biallelic mutations in each of the cases studied, and in vivo testing confirmed a loss of expressed protein. All eight cases assayed showed elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type I interferon in the genesis of autoimmunity.

Topics: Acid Phosphatase; Animals; Autoimmunity; Bone Diseases, Developmental; Cattle; Chromosomes, Human, Pair 19; Female; Gene Expression Regulation; Humans; Inflammation; Interferon Type I; Isoenzymes; Lupus Erythematosus, Systemic; Male; Models, Molecular; Mutation; Mutation, Missense; Phenotype; Sclerosis; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Alleles; Autoantibodies; Autoimmune Diseases; Autoimmunity; Brain; Genes, Recessive; HLA Antigens; Humans; Isoenzymes; Lupus Erythematosus, Systemic; Mutation; Osteochondrodysplasias; Osteopontin; Phosphorylation; Risk; Syndrome; Tartrate-Resistant Acid Phosphatase

The aim of this study was to assess the skeletal metabolism in a murine model of systemic lupus erythematosus (SLE). MRL/n and MRL/l mice (respectively representing a benign and a malignant form of the disease) were observed from 1.5 to 6.5 months of life. The monthly follow-up included: biochemical and histomorphometrical studies of the femoral bone, serum biochemistry, immunoglobulins and osteocalcin, and histological evaluation of the kidney tissue. The results showed a higher femoral weight (+11.5%), calcium (+4.4%) and protein bone content (+11.4%) and a significantly higher (+77%) phosphorus bone content in the MRL/n group; significantly lower (-48.9%) bone alkaline phosphatase enzymatic activity, lower bone alkaline/acid phosphatase enzymatic activities ratio (-40.8%) and lower (-38.4%) serum osteocalcin values in the MRL/l group (which might suggest reduced bone formation in these animals); markedly smaller trabecular bone volume (BV/TV) in the femoral head (-36.2%) and femoral neck (-39.8%), and smaller cortical and femoral areas in the mid-femoral shaft (-38.8% and -38.1% respectively) in the MRL/l group; higher serum immunoglobulins, increased serum blood urea nitrogen (BUN) and creatinine and a higher index of activity in the kidney histology in the MRL/l group, indicating increased activity of the disease in this substrain. The MRL mice, through their two substrains, may serve as a valuable laboratory animal model for study of the skeletal changes in SLE and of the influence of the disease activity on the skeletal metabolism.

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Calcium; Disease Models, Animal; Femur; Lupus Erythematosus, Systemic; Magnesium; Mice; Mice, Inbred MRL lpr; Organ Size; Osteocalcin; Osteoporosis; Phosphorus

A simple immunohistological test has been developed to detect and to quantitate the presence of immune complexes (IC) on the surface of human polymorphonuclear neutrophils (PMN). The interaction between IC and PMN has been evaluated in several human IC diseases. High amounts of immunoglobulins (Ig) and C3 were detected on the PMN surface from these patients. The deposits of Ig and C3 were inversely related to the percentage of membrane-free receptors for Fc and C3.

Topics: Acid Phosphatase; Alkaline Phosphatase; Humans; Immune Complex Diseases; L-Lactate Dehydrogenase; Lupus Erythematosus, Systemic; Neutrophils; Phagocytosis; Polyethylene Glycols; Receptors, Antigen, B-Cell

Topics: Acid Phosphatase; Animals; Cathepsins; Chediak-Higashi Syndrome; Cyclic AMP; Dermatitis; Fabry Disease; Humans; Keratins; Lupus Erythematosus, Systemic; Lysosomes; Psoriasis; Skin; Ultraviolet Rays; Vacuoles; Vitamin A Deficiency

Topics: Acid Phosphatase; Adolescent; Adult; Cathepsins; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Female; Humans; Leukocytes; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic; Male; Middle Aged; Peroxidases

Topics: Acid Phosphatase; Amyloidosis; Glomerulonephritis; Glycerolphosphate Dehydrogenase; Humans; Lupus Erythematosus, Systemic; Lymphocytes; Nephrotic Syndrome; Succinate Dehydrogenase

Topics: Acid Phosphatase; Alkaline Phosphatase; Amyloidosis; Familial Mediterranean Fever; Glomerulonephritis; Histocytochemistry; Humans; Lupus Erythematosus, Systemic; Neutrophils; Peroxidases

Topics: Acid Phosphatase; Alkaline Phosphatase; Amyloidosis; Glomerulonephritis; Glycerolphosphate Dehydrogenase; Humans; Leukocytes; Lupus Erythematosus, Systemic; Nephrotic Syndrome; Neutrophils; Peroxidases; Purpura; Succinate Dehydrogenase

Topics: Acid Phosphatase; Acute Disease; Alkaline Phosphatase; Bacterial Infections; Carbon Isotopes; Citric Acid Cycle; Glucose; Glucosephosphate Dehydrogenase; Glutathione Reductase; Humans; Lupus Erythematosus, Systemic; Neoplasms; Neutrophils; Osteomyelitis; Oxygen Consumption; Peroxidases; Phosphogluconate Dehydrogenase; Pyruvate Kinase; Tetrazolium Salts; Tuberculosis, Pulmonary; Virus Diseases

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Animals; Antibody Formation; Antigens; Cholelithiasis; Female; Glucuronidase; Hexosaminidases; Histocytochemistry; Humans; Lupus Erythematosus, Systemic; Lymph Nodes; Lymphocytes; Male; Peroxidases; Plasma Cells; Rabbits; Rats; Sarcoidosis; Stomach Neoplasms; Stomach Ulcer; Tuberculosis

Topics: Acid Phosphatase; Adult; Aged; Arthritis, Rheumatoid; Collagen Diseases; Humans; Knee Joint; Lupus Erythematosus, Systemic; Middle Aged; Rheumatoid Factor; Synovial Fluid; Synovitis

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Rheumatoid; Collagen Diseases; Dermatomyositis; Humans; Lupus Erythematosus, Systemic; Nephritis; Neutrophils; Peroxidases; Prednisolone

Topics: Acid Phosphatase; Adolescent; Adult; Arthritis, Rheumatoid; Cell Membrane; Female; Histocytochemistry; Humans; Lupus Erythematosus, Systemic; Lymphocytes; Lysosomes; Male; Middle Aged; Osmotic Fragility