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I N Targoff

Publications and source records attributed to I N Targoff.

At least 19 recordsLinked to original sources
PubMed1992

Antibodies to glycyl-transfer RNA synthetase in patients with myositis and interstitial lung disease.

OBJECTIVE: We have previously described anti-EJ antibodies, and provided evidence that these antibodies react with glycyl-transfer RNA (gly-tRNA) synthetase. The aim of the present study was to identify patients with anti-EJ antibodies and describe the clinical associations of the antibody, in particular, whether it is associated with the syndrome of myositis and interstitial lung disease (ILD) that has been previously associated with autoantibodies to the aminoacyl-tRNA synthetases for histidine, threonine, and alanine. METHODS: Sera from patients with suspected or proven polymyositis or dermatomyositis (DM), sera with anticytoplasmic patterns, and control sera were tested for anti-EJ antibodies by immunoprecipitation (IPP). Positive sera and controls were tested for the ability to inhibit gly-tRNA synthetase by preincubation of the enzyme source with the serum. RESULTS: Anti-EJ antibodies were demonstrated in the sera of 5 patients, by IPP of characteristic tRNAs and protein. Original serum EJ and each of the new sera significantly inhibited the enzymatic activity of gly-tRNA synthetase but not histidyl-tRNA synthetase. All 5 of the new patients had inflammatory myopathy, a typical DM rash, and ILD. One, who had an overlap syndrome with systemic lupus erythematosus, had anti-EJ at least 4 months before the development of clinical myositis. Arthritis and Raynaud's phenomenon, other features associated with antisynthetases, were also seen. CONCLUSION: Anti-EJ is associated with the syndrome of myositis and lung disease that is seen in association with other antisynthetases. The finding of specific inhibition of gly-tRNA synthetase by all anti-EJ-positive sera strongly supports the identification of EJ antigen as gly-tRNA synthetase.

Adult↗
PubMed1992

Cloning of a complementary DNA coding for the 100-kD antigenic protein of the PM-Scl autoantigen.

Anti-PM-Scl antibodies are associated with polymyositis-scleroderma overlap or either disease alone. Among sera from 39 patients with anti-PM-Scl, 23 recognized the 100-kD band in immunoblot against HeLa cell extract, 16 of which also stained the 70-kD band. A human thymocyte lambda gt11 cDNA expression library was screened with anti-PM-Scl serum, and two clones were identified whose products reacted with 33 and 37 of 39 anti-PM-Scl sera, respectively, but none of 26 negative control sera. Affinity-purified antibody reacting specifically with plaques of the clone stained the 100-kD band on immunoblot, reacted with nucleoli of HEp-2 cells, and immunoprecipitated the PM-Scl protein complex. Partial sequences of both inserts were identical. One insert was fully sequenced, and additional 5' and 3' sequence was obtained using a gene-specific primer to form a cDNA with HeLa cell RNA as template followed by PCR. The complete nucleotide sequence included 2,739-bp coding for a predicted full-length protein of 98,088 D. There was no homology with the PM-Scl 75-kD protein and no significant homology with other proteins. A mixed-charge cluster was identified, with 22 charged amino acids of 37. In conclusion, the full-length cDNA sequence was determined coding for the PM-Scl 100-kD protein, the most commonly antigenic protein of the PM-Scl complex.

Amino Acid Sequence↗
PubMed1992

Autoantibodies in polymyositis.

A group of autoantibodies have been identified that are found almost exclusively in patients with polymyositis and dermatomyositis (myositis-specific antibodies). Most have been associated with characteristic clinical subgroups. Five of the myositis-specific antibodies are directed at aminoacyl-tRNA synthetases and have been associated with a similar clinical syndrome marked by myositis, interstitial lung disease, arthritis, and Raynaud's phenomenon (antisynthetase syndrome). Myositis-specific antibodies can help with patient diagnosis, subgroup classification, and possible prognosis. Their role in the pathogenesis of myositis remains to be defined, but their production is genetically influenced and appears to be linked to fundamental etiologic factors.

Amino Acyl-tRNA Synthetases↗
PubMed1991

Distinct seasonal patterns in the onset of adult idiopathic inflammatory myopathy in patients with anti-Jo-1 and anti-signal recognition particle autoantibodies.

In idiopathic inflammatory myopathy (IIM; or, polymyositis/dermatomyositis), the myositis-specific autoantibodies anti-Jo-1 and anti-signal recognition particle (anti-SRP), appear to define clinically and immunogenetically distinct groups of patients. We show here that the month during which the onset of weakness occurs is not random in patients with anti-Jo-1 auto-antibodies (average month April, P less than 0.02) and in those with anti-SRP autoantibodies (average month November, P less than 0.02); both groups of patients also experience rapid onset of disease. By contrast, patients classified into the traditional categories of polymyositis and dermatomyositis do not have recognizable seasonal patterns and do not differ in the rate of onset of disease. These findings suggest that searches for seasonal patterns in the onset of autoimmune disorders characterized by disease-specific autoantibodies may provide useful clues to etiology.

Adult↗
PubMed1991

A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups.

The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy.

Adult↗
PubMed1991

Clinical, serologic, and immunogenetic studies in patients with dermatomyositis.

Dermatomyositis is a disease of unknown etiology characterized by progressive, symmetrical, proximal muscle weakness with accompanying compatible cutaneous findings. Thirty-nine patients with dermatomyositis from the Louisville, Kentucky area were enrolled in this study. Patients were grouped into those with or without a malignancy. Ten patients (26%) either had or have had a malignancy. Twenty-five Caucasian patients were HLA typed for the A, B, DR and DQ locus antigens, of whom 5 had an associated malignancy and 20 did not have a malignancy. We found that no single antigen had a significantly increased or decreased frequency as compared with our control population for the entire group, or for any clinical subset we examined. Serologic testing revealed 4 patients with anti-Mi-2 antibodies and 1 patient with anti-PM-SCL antibodies. No patient had a positive anti-Jo-1 antibody in this group. The results of serologic tests in this group did not correlate with any clinical subset or HLA antigen. Our findings were in agreement with the previous reports in which approximately 25% of patients with DM have an associated malignancy. Our findings also support the notion that untargeted malignancy searches are not warranted. Contrary to previous reports we did not observe an inverse relationship between cancer and pulmonary disease in the dermatomyositis patient. This study does not indicate that there are any HLA associations or clinical associations, other than age, that distinguish patients with dermatomyositis as running a greater risk of developing malignancy.

Dermatomyositis↗
PubMed1991

Polymyositis.

Explore the source record for details and available documents.

Animals↗
PubMed1990

Autoantibodies to aminoacyl-transfer RNA synthetases for isoleucine and glycine. Two additional synthetases are antigenic in myositis.

Autoantibodies to three of the aminoacyl-transfer RNA (tRNA) synthetases have been reported (for histidine, threonine, and alanine). Most patients with these autoantibodies have polymyositis, and the majority also have interstitial lung disease. This study examined the question of whether autoantibodies to other aminoacyl-tRNA synthetases occur in the sera of myositis patients. We tested sera from patients with myositis with unidentified anticytoplasmic antibodies that immunoprecipitate tRNA for the ability to inhibit the aminoacyl-tRNA synthetases for the remaining 17 amino acids. Three sera showed strong inhibitory activity for a synthetase. OJ and NJ sera (and IgG) significantly inhibited isoleucyl-tRNA synthetase activity, each with 94% inhibition at the screening dilution, whereas other test sera and controls all inhibited less than 50%. OJ and NJ sera immunoprecipitated identical patterns of tRNA, and identical, complex patterns of high m.w. polypeptides that were consistent with the multienzyme synthetase complex of which isoleucyl-tRNA synthetase is a part. EJ serum (and IgG) significantly inhibited glycyl-tRNA synthetase, and immunoprecipitated a unique pattern of transfer RNA, and a strong predominant protein band of 77 kDa. These data strongly suggest that OJ and NJ have autoantibodies to isoleucyl-tRNA synthetase, and that EJ has antibodies to glycyl-tRNA synthetase. The findings of signs of muscle involvement in all three patients, and severe interstitial lung disease in OJ, strengthens the association of antisynthetases with these conditions.

Amino Acyl-tRNA Synthetases↗
PubMed1990

HLA-D region genes associated with autoantibody responses to histidyl-transfer RNA synthetase (Jo-1) and other translation-related factors in myositis.

Myositis has been associated with HLA-B8 and DR3, especially in white patients with polymyositis and serum anti-Jo-1 antibodies. Twenty-eight patients with myositis and serum translation-related autoantibodies anti-Jo-1, anti-PL-7, anti-PL-12, anti-KJ, and anti-SRP were studied for HLA class II specificities by Southern blotting with HLA-DR beta, DQ beta, and DQ alpha probes. The association of HLA-DR3 (DRw17) with anti-Jo-1 antibodies in white myositis patients was confirmed (P = 0.003, relative risk 8.9). However, HLA-DRw52 haplotypes, regardless of subtype, were present in all of the white and black patients with serum anti-Jo-1 and other translation-related autoantibodies. Moreover, one anti-Jo-1 positive patient had HLA-DRw8, an HLA-DRw52 haplotype on which the DR beta 3 gene has been partially deleted. No HLA-DQ specificity or allele was common to all patients. The HLA-DR3, DR5, DRw6, and DRw8 haplotypes, which bear the HLA-DRw52 specificity, share the most homology in the DR beta 1 first hypervariable region at amino acid positions 9-13. Thus, this DR beta 1 region appears to be the most likely candidate "epitope" for translation-related autoimmune responses in inflammatory myositis.

Alleles↗
PubMed1990

Antibody to signal recognition particle in polymyositis.

Using immunoprecipitation, we identified 13 patients with antibodies to the signal recognition particle (SRP) from a collection of sera representing 265 polymyositis/dermatomyositis (PM/DM) patients. Antibody reactivity with SRP was confirmed by enzyme-linked immunosorbent assay and immunoprecipitation with isolated dog pancreas SRP. The antibody was present in the serum of 4% of PM/DM patients, and 18% of PM/DM patients with anticytoplasmic antibodies other than anti-Jo-1, but not in patients with other conditions who had anticytoplasmic antibodies. Anti-SRP was associated with classic adult PM, and some of these cases were unusually severe and/or of rapid onset; it was not found in patients with overlap syndromes or with DM involvement. Unlike patients with antibodies to aminoacyl-transfer RNA synthetases, patients with anti-SRP had a low frequency of pulmonary fibrosis, as well as of arthritis and Raynaud's phenomenon. Anti-SRP antibodies may serve as a marker for a second, distinct subgroup of adult PM.

Adult↗
PubMed1990

Clinical manifestations in patients with antibody to PL-12 antigen (alanyl-tRNA synthetase).

PURPOSE: Anti-PL-12 antibody is directed at the enzyme alanyl-tRNA synthetase (ARS). Studies have clearly associated anti-Jo-1, also directed at an aminoacyl-tRNA synthetase (histidyl-tRNA synthetase), with a subgroup of myositis marked by a high frequency of interstitial lung disease (ILD) and arthritis. A similar syndrome has been reported in patients with antibodies to PL-12, but few patients have been studied. We describe the clinical manifestations in a new series of patients with antibody to PL-12. PATIENTS AND METHODS: Sera from patients with polymyositis and sera found to contain anticytoplasmic antibodies were screened for antibody to PL-12 by testing for inhibition of ARS enzymatic activity by serum, and by immunoprecipitation. RESULTS: Nine sera inhibited ARS. These nine plus two additional sera with anticytoplasmic antibodies immunoprecipitated an identical pattern of tRNAs and a polypeptide of 110 kd. Of the 10 patients that could be evaluated, eight had some evidence of myositis, including six that satisfied the criteria for myositis. Three of these six, all with dermatomyositis, had severe muscle involvement. Eight of the 10 patients had radiographic evidence of pulmonary fibrosis, and seven of the eight had clinical pulmonary impairment, including four with clinically severe ILD. Joint manifestations were found in five patients, and arthritis was the only clinical problem in one patient. CONCLUSION: We conclude that anti-PL-12, like anti-Jo-1 and anti-PL-7, was frequently associated with the "Jo-1 syndrome" of myositis with ILD. ILD was a major clinical problem in this group of patients.

Adult↗
PubMed1990

C4 null genes in American whites and blacks with myositis.

The frequencies of C4A and C4B alleles were determined in 66 adults with myositis in relation to HLA class I and II. In whites with myositis, the C4A*Q0 allele occurred in 13/31 (47%) as compared to 25/101 (25%) normal controls (p = 0.08, relative risk = 2.7). Only 11/35 (31%) of black patients with myositis had a C4A*Q0 allele compared to 11/55 (20%) of controls (p = NS, RR = 1.8). Thus, the MHC class III genes do not appear to be the primary genetic risk factors for myositis in adults.

Alleles↗
PubMed1989

Anti-KJ: a new antibody associated with the syndrome of polymyositis and interstitial lung disease.

Antibodies to aminoacyl-tRNA synthetases (anti-Jo-1, anti-PL-7, anti-PL-12) have been found in the serum of some patients with polymyositis (PM). Patients with these antibodies have an unusually high rate of interstitial lung disease (ILD) in association with their PM. Two patients (K.J. and B.T.) with severe ILD and PM were found to have antibodies to a cytoplasmic antigen, but tests to determine whether the antigen was an aminoacyl-tRNA synthetase were negative, including tests of KJ serum for inhibitory effects on the 20 synthetases. KJ immunoprecipitates did not contain tRNA, in contrast to antisynthetase sera. When IgG samples were added to a reticulocyte in vitro translation system at a concentration of 0.3 mg/ml, KJ IgG inhibited globin mRNA translation by 98%, while anti-Jo-1 IgG inhibited 62% and normal IgG had little effect. Thus, both anti-KJ and the antisynthetases are directed at antigens that are involved in translation and protein synthesis, and both are associated with the syndrome of lung disease and PM. This syndrome may be associated with antibodies to translation-related proteins in general, which may have implications for the link of PM and enteroviruses, which are mRNA viruses.

Adult↗
PubMed1988

Antibody to threonyl-transfer RNA synthetase in myositis sera.

The prevalence and clinical correlations of anti-threonyl-transfer RNA synthetase (anti-PL-7), as well as the relationship of anti-PL-7 to anti-histidyl-transfer RNA synthetase (anti-Jo-1) were studied in 109 sera from patients with myositis. Inhibition of threonine aminoacylation was used to screen for anti-PL-7. Sera from 3 patients, 2 with polymyositis and 1 with polymyositis-overlap syndrome, and a fourth serum from a patient with dermatomyositis, which was previously found to contain anti-PL-7, inhibited greater than 90% of activity (3.7% of 109 sera). All 4 sera reacted strongly in an enzyme-linked immunosorbent assay with enzyme that was either affinity purified with anti-PL-7 or was biochemically purified. There was no indication of cross-reactivity by aminoacylation inhibition or, for most sera, by enzyme-linked immunosorbent assay. Anti-PL-7 is an uncommon myositis-associated antibody that is independent of anti-Jo-1, but is directed at a functionally related enzyme.

Acylation↗