Antibodies to a nuclear/nucleolar antigen in patients with polymyositis overlap syndromes

Reichlin, Morris; Maddison, Peter J.; Targoff, Ira N.; Bunch, Thomas W.; Arnett, Frank C.; Sharp, Gordon C.; Treadwell, Edward L.; Tan, Eng M.

doi:10.1007/bf00915286

Cited by 175 publications

(76 citation statements)

References 8 publications

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“…The estimated molecular masses of the proteins found in these studies were 110, 90, 80, 39,37,33,30,27,26,22, and 20 kDa. Comparison of these molecular masses with those of the proteins characterized in the present study suggested that hRrp40, hRrp41 and hRrp46 correspond to the 30-, 27-, and 26-kDa proteins, respectively.…”

Section: Cloning Of Human Homologues Of Yeast Rrp40pmentioning

confidence: 65%

“…This complex, initially designated as the polymyositis/scleroderma (PM/Scl) 1 overlap syndrome particle and herein referred to as the human exosome, was reported to contain 11 (25) to 16 (26) subunits ranging from 20 to 110 kDa. Two proteins of this complex were identified as autoantigens, which are targeted by autoantibodies present in the serum of patients suffering from myositis, scleroderma, or PM/Scl overlap syndrome (27). All tested anti-PM/Scl-positive sera recognize a nuclear protein, known as PM/Scl-100, while some also recognize a protein migrating at about 75 kDa (PM/ Scl-75) in SDS-polyacrylamide gel electrophoresis (28 -30).…”

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confidence: 99%

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Three Novel Components of the Human Exosome

Brouwer

Allmang

Raijmakers

et al. 2001

Journal of Biological Chemistry

101

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The yeast exosome is a complex of 3 3 5 exoribonucleases. Sequence analysis identified putative human homologues for exosome components, although several were found only as expressed sequence tags. Here we report the cloning of full-length cDNAs, which encode putative human homologues of the Rrp40p, Rrp41p, and Rrp46p components of the exosome. Recombinant proteins were expressed and used to raise rabbit antisera. In Western blotting experiments, these decorated HeLa cell proteins of the predicted sizes. All three human proteins were enriched in the HeLa cells nucleus and nucleolus, but were also clearly detected in the cytoplasm. Size exclusion chromatography revealed that hRrp40p, hRrp41p, and hRrp46p were present in a large complex. This cofractionated with the human homologues of other exosome components, hRrp4p and PM/ Scl-100. Anti-PM/Scl-positive patient sera coimmunoprecipitated hRrp40p, hRrp41p, and hRrp46p demonstrating their physical association. The immunoprecipitated complex exhibited 3 3 5 exoribonuclease activity in vitro. hRrp41p was expressed in yeast and shown to suppress the lethality of genetic depletion of yeast Rrp41p. We conclude that hRrp40p, hRrp41p, and hRrp46p represent novel components of the human exosome complex.In both bacteria and eukaryotes, the processing and degradation of many RNA species involves multiprotein complexes (reviewed in Refs. 1-4). The Escherichia coli degradosome includes the endoribonuclease E (RNase E), the 3Ј 3 5Ј exonuclease polynucleotide phosphorylase, the DEAD box RNA helicase RhlB, and several additional proteins whose role is unclear (5-7). Related complexes are implicated in RNA processing in chloroplasts and mitochondria (8 -10). The yeast exosome contains at least 11 components, which are known or predicted to be 3Ј 3 5Ј exoribonucleases (11,12). Ten of these (Rrp4p, Rrp40 -46p, Mtr3p, and Csl4p) have been demonstrated to be encoded by essential genes. These 10 components were found in both cytoplasmic and nuclear complexes, whereas the nonessential RRP6 gene product was detected only in the nucleus (11, 13).The 3Ј processing of many RNAs is affected by the absence or mutation of exosome components. The nuclear exosome is implicated in the processing of ribosomal RNA (rRNA), spliceosomal small nuclear RNAs, and small nucleolar RNAs, as well as the degradation of pre-rRNA spacers and unspliced pre-mRNAs (12-22). The cytoplasmic exosome complex is involved in the 3Ј 3 5Ј pathway of mRNA degradation (22). The activity of the exosome complex may be regulated by cofactors including, for example, the putative ATP-dependent DEVH box RNA helicases Dob1p and Ski2p (23,24).Human cells also contain a multiprotein complex that is related to the yeast exosome (11). This complex, initially designated as the polymyositis/scleroderma (PM/Scl) 1 overlap syndrome particle and herein referred to as the human exosome, was reported to contain 11 (25) to 16 (26) subunits ranging from 20 to 110 kDa. Two proteins of this complex were identified as autoantigens, which are tar...

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Section: Cloning Of Human Homologues Of Yeast Rrp40pmentioning

confidence: 65%

mentioning

confidence: 99%

Three Novel Components of the Human Exosome

Brouwer

Allmang

Raijmakers

et al. 2001

Journal of Biological Chemistry

101

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“…None of the other specificities is primarily associated with DM. Anti-PM-Scl is seen with about equal frequency in PM and DM, although it is particularly associated with myositis-scleroderma overlap (2). Anti-Jo-1 is much more frequently seen in PM than in DM (3).…”

Section: Discussionmentioning

confidence: 99%

The association between Mi‐2 antibodies and dermatomyositis

Targoff¹,

Reichlin²

1985

Arthritis & Rheumatism

240

128

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Antibodies to Mi, an antigen in calf thymus extract, have been demonstrated by complement fixation inhibition in polymyositis (PM) and dermatomyositis (DM) sera but not in the sera of individuals without myositis. The original Mi reference serum defined 2 precipitating antibodies, using immunodiffusion (ID). Anti‐Mi‐1 was not active in complement fixation. We have now studied in further detail anti‐Mi‐2, which appears to be the antibody in Mi serum that fixes complement. Mi‐2 antigen was purified by immunoaffinity chromotography. An enzyme‐linked immunosorbent assay (ELISA) to measure Mi‐2 antibody, using this antigen, was used to test the sera of 139 myositis patients: 52 had DM and 87 had PM. Control sera from 35 normal subjects and 93 patients with other connective tissue diseases were also tested. Only 13 sera were considered definitely positive for anti‐Mi‐2. All were from patients who had myositis, 11 of whom had DM. Only DM sera had anti‐Mi‐2 by ID, and all sera with anti‐Mi‐2 by ID were positive by ELISA. A number of other sera, including many from patients with other connective tissue diseases and 2 from normal subjects (all without precipitating antibodies) had lower elevations which were of uncertain significance. Detection of anti‐Mi‐2 by ID as well as by ELISA was significantly more frequent in DM than in PM. Anti‐Mi‐2 appears to be closely linked to DM, and is the first specific serologic marker for this form of myositis.

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“…The followup period was <5 years in 85 patients, [5][6][7][8][9][10] years in 53 patients, and > 10 years in 75 patients. During the period of observation, 99 patients received corticosteroids (mean maximum dosage 33 mg of prednisone equivalent daily), 23 received D-penicillamine, and 16 received cytotoxic drugs (11 took azathioprine, 3 methotrexate, and 2 mizoribine).…”

Section: Methodsmentioning

confidence: 99%

Clinical and Prognostic Associations Based on Serum Antinuclear Antibodies in Japanese Patients with Systemic Sclerosis

Kuwana

Kaburaki

Okano

et al. 1994

Arthritis & Rheumatism

260

225

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Objective. To clarify the clinical features and prognosis of systemic sclerosis (SSc) based on serum antinuclear antibodies (ANA). Methods. We studied 275 consecutive Japanese patients newly diagnosed as having SSc, who were first evaluated during the period 1971—1990. Eight SSc–related ANA were identified using indirect immunofluorescence, double immunodiffusion, or immunoprecipitation assays. Clinical and prognostic features were retrospectively analyzed in patient groups, categorized by their serum ANA. Results. Cumulative survival rates at 10 years after diagnosis of SSc were 93% in patients with anticentromere antibodies (ACA), 72% in those with anti—U1 RNP, 66% in those with anti—DNA topoisomerase I (anti—topo I), and 30% in those with anti‐RNA polymerases I, II, and III (anti‐RNAP). Major organ involvement linked to cause of death included biliary cirrhosis in patients with ACA, isolated pulmonary arterial hypertension and cerebral hemorrhage in those with anti—U1 RNP, pulmonary interstitial fibrosis in those with anti—topo I, and cardiac and renal involvement in those with anti‐RNAP. Conclusion. Determinations of serum ANA in SSc patients are useful in predicting organ involvement and long‐term outcome.

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Antibodies to a nuclear/nucleolar antigen in patients with polymyositis overlap syndromes

Cited by 175 publications

References 8 publications

Three Novel Components of the Human Exosome

Three Novel Components of the Human Exosome

The association between Mi‐2 antibodies and dermatomyositis

Clinical and Prognostic Associations Based on Serum Antinuclear Antibodies in Japanese Patients with Systemic Sclerosis

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