Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteinase-3 (PR-3) is a neutral serine proteinase present in the azurophil granules of human polymorphonuclear leukocytes. It degrades a variety of extracellular matrix proteins including elastin in vitro and causes emphysema when administered by tracheal insufflation to hamsters. It is identical to the target autoantigen (c-ANCA) associated with Wegener's granulomatosis and to myeloblastin, a serine proteinase first identified in HL-60 leukemia cells. In this study, the gene encoding PR-3 was cloned and sequenced. The gene spans approximately 6.5 kilobase pairs and consists of five exons and four introns. The genomic organization of PR-3 is similar to that of the other serine proteinases expressed in hemopoietic cells. Each residue of the catalytic triad of PR-3 is located on a separate exon, and the positions of the residues within the exons are similar to those in human leukocyte elastase and cathepsin G. The phase and placement of the introns in the PR-3 gene are also similar to those in human leukocyte elastase and cathepsin G. The 400-base pair (bp) 5'-flanking sequence of the PR-3 gene contains a TATA box at position 379. There is no CAAT box promoter element. The 3'-untranslated region is 200 bp, extending from a TGA stop codon to the site of polyadenylation 10 bp after the canonical AATAAA signal. Amplification of PR-3 from a human/hamster hybrid cell line localizes the gene to human chromosome 19. Evidence from Northern analysis suggests that PR-3 expression is primarily confined to the promyelocytic/myelocytic stage of bone marrow development.
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PMID:Structure, chromosomal assignment, and expression of the gene for proteinase-3. The Wegener's granulomatosis autoantigen. 140 Apr 30

Alpha1-antitrypsin (D,1AT) is the most abundant circulating protease inhibitor (Pi) in human plasma. It has central function in controlling tissue degradation by inhibiting a large number of proteases including neutrophil elastase and proteinase 3 (PR3). PR3, the Wegner's autoantigen, has been suggested to be involved in the pathogenesis of small-vessel systemic vasculitides. alpha1 AT deficiency (PiZ) is frequent in Caucasian populations, and its homozygous state (PiZZ) is known to predispose to lung emphysema and chronic liver disease. A strong correlation between heterozygous (PiZ) and homozygous (PiZZ) alpha1 AT deficiency and anti-neutrophil cytoplasmic autoantibodies (ANCA) associated systemic nocrotizing vasculitides has recently been reported in various populations. In this review the pathogenesis of small-vessel vasculitides is outlined, focusing on the role of alpha1 AT deficiency. alpha1 AT has been suggested to have a crucial role as a protective protein in ANCA-associated vasculitic syndromes.
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PMID:The role of alpha1 -antitrypsin Deficiency in the Pathogenesis of Antineutrophil Cytoplasmic Antibodies Associated Systemic Necrotizing Vasculitides. 1821 13

The role of autoimmune pathology in development and progression of chronic obstructive pulmonary disease (COPD) is becoming increasingly appreciated. In this study, we identified serum autoantibody reactivities associated with chronic bronchitis or emphysema, as well as systemic autoimmunity and associated lung disease. Using autoantigen array analysis, we demonstrated that COPD patients produce autoantibodies reactive to a broad spectrum of self-antigens. Further, the level and reactivities of these antibodies, or autoantibody profile, correlated with disease phenotype. Patients with emphysema produced autoantibodies of higher titer and reactive to an increased number of array antigens. Strikingly, the autoantibody reactivities observed in emphysema were increased over those detected in rheumatoid arthritis patients, and included similar reactivities to those associated with lupus. These findings raise the possibility that autoantibody profiles may be used to determine COPD risk, as well as provide a diagnostic and prognostic tool. They shed light on the heterogeneity of autoantibody reactivities associated with COPD phenotype and could be of use in the personalization of medical treatment, including determining and monitoring therapeutic interventions.
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PMID:COPD is associated with production of autoantibodies to a broad spectrum of self-antigens, correlative with disease phenotype. 2294 90