Antibodies to cytoplasmic antigens in lupus erythematosus

Seven patients with classic cutaneous lupus ery-thematosus are described. Three of these patients had features satisfying four of the American Rheumatism Association (ARA) preliminary criteria for the diagnosis of systemic lupus erythematosus (SLE). Their sera, however, lacked antinuclear antibodies but demonstrated precipitating antibodies reactive against cytoplasmic RNP (La) and non-nucleic acid (Ro) antigens. Four additional ANA-negative patients lacking significant skin disease but having a lupus-like multisystem disease were found to have antibodies to soluble cytoplasmic antigens. Thirty-three of 130 ANA-positive SLE patients, but none of 16 discoid lupus patients, possessed these anticytoplasmic antibodies. These findings suggest that antibodies to Ro and La may be a marker for systemic disease in ANA-negative patients with 1) cutaneous lupus and 2) a distinct sub-population of patients with a lupus-like syndrome without skin disease.     

Clinical associations of IgG antibodies to the ribonucleoprotein p67 polypeptide in patients with systemic lupus erythematosus.

The ribonucleoprotein (RNP) p67 antigen was purified from rabbit thymus and used in an enzyme linked immunosorbent assay (ELISA) with low interassay variability to detect IgG antibodies to p67 in patients with autoimmune connective tissue diseases. These antibodies were found in eight (80%) patients with a clinical diagnosis of mixed connective tissue disease (MCTD) but also in 27 (40%) patients with systemic lupus erythematosus (SLE). Sixty six per cent of the 12 patients with SLE with high levels of antibodies to p67 (> 50 U) had three or more features of MCTD, including myositis, fibrosing alveolitis, Raynaud's phenomenon, and sclerodactyly. Antibodies to the p67 RNP were not associated with the presence or absence of renal disease in the patients with SLE. This study suggests that antibodies against the p67 RNP are markers for clinical features of MCTD even in the context of SLE.     

Lupus-like presentation of parvovirus B19 infection

OBJECTIVES: To describe 2 cases of parvovirus B19 (B19) infection mimicking systemic lupus erythematosus (SLE) and to identify all cases of SLE imitated by and/or associated with B19 in the medical literature. METHODS: A computer-assisted (PubMed) search of the medical literature from 1975 to 2003 was performed using the following key words: parvovirus, B19, SLE, lupus, antibodies, auto-immunity. RESULTS: Thirty-eight patients were identified: 35 women, 3 men; mean age = 28.8 years. Clinical manifestations were as follows: fever (24 patients); articular involvement (36 patients); cutaneous lesions (28 patients); lymphadenopathy (9 patients); hepato- and/or splenomegaly (6 patients); serositis (6 patients); renal involvement (4 patients); cerebral impairment (10 patients). Cytopenia was observed in 23 cases. Antinuclear antibodies were detected in 34 patients, anti-double-stranded DNA antibodies in 20 patients, anti-Sm antibodies in 4 patients, antinuclear ribonucleoprotein antibodies in 5 patients, anti-Ro-SSA antibodies in 4 patients, anti-La-SSB antibodies in 4 patients, and anticardiolipin and/or anti-beta2-glycoprotein I antibodies in 8 patients. Hypocomplementemia was found in 15 of 26 patients. In 19 cases, the B19 infection had a self-limiting course. In 6 cases, B19 infection occurred in a context of previously established SLE, simulating SLE exacerbation. In 6 observations, symptoms persisted several months after the viral infection. In 7 cases, the exact relationship between SLE and B19 could not be determined. CONCLUSIONS: B19 infection may present a clinical and serological tableau making it difficult to distinguish between a viral infection and the first episode of SLE. Although B19 may modulate the clinical and biological features of rheumatic disease, studies in large series do not support a causative role for B19 in the pathogenesis of SLE.     

The SL autoantibody-antigen system: clinical and biochemical studies.

A recently described autoantibody, SL, was found in serum from 27 patients with autoimmune disease, including 20 with systemic lupus erythematosus (SLE) where the frequently was 7%. Analysis of clinical, serological, and HLA data from 119 SLE patients showed no positive associations with anti-SL antibody apart from a higher frequency of non-infective fever. Most SL positive sera contained other precipitins, notably antibodies to Ro(SS-A) and the proliferating cell nuclear antigen, PCNA. Anti-SL IgG recognised a protein of 32 000 daltons without associated RNA. This polypeptide was distinguished from a similarly sized component of the Sm and RNP ribonucleoprotein particles by demonstrating different products of partial proteolysis. Although anti-SL antibody is of limited clinical importance, it occurs with twice the frequency of anti-SM antibody in white patients with SLE. Preliminary studies indicate that SL and the Japanese Ki system are identical.     

Cellular regulation of anti-nRNP antibody synthesis is different from that of anti-DNA antibody synthesis in patients with systemic lupus erythematosus

Summary The cellular regulation of anti-nuclear ribonucleoprotein (nRNP) antibody synthesis in patients with systemic lupus erythematosus (SLE) was examined and compared with that of anti-double-stranded DNA (dsDNA) antibodies. In vitro antibody production by lymphocytes from SLE patients with antibodies to either dsDNA or nRNP alone was measured using dsDNA-specific and nRNP-specific solid-phase radioimmunoassays (RIA). Lymphocytes of SLE patients with only anti-dsDNA antibodies and normal individuals failed to synthesize anti-nRNP antibody with or without nRNP stimulation. In contrast, lymphocytes from SLE patients with anti-nRNP antibody alone in their sera synthesized in vitro a large amount of anti-nRNP antibody with or without nRNP stimulation. Experiments with reconstituted autologous lymphocytes indicated that B cells and T cells were required for anti-nRNP antibody synthesis. As expected, helper function for antibody synthesis by autologous B cells resided in the T4-cell population and suppressor function in the T8-cell population. T8 cells from SLE patients with anti-nRNP antibody alone suppressed anti-nRNP antibody synthesis by autologous B cells irrespective of clinical activity. This is in contrast to anti-dsDNA antibody production, which was not suppressed by autologous T8 cells. These results indicate that the cellular regulation of anti-nRNP antibody synthesis in SLE is different from that of anti-dsDNA antibody syntheis. Increased anti-nRNP antibody synthesis may be due to increased T4-helper cell function rather than defective T8-suppressor function.     

Frequency and clinical significance of antibodies to ribonucleoprotein in SLE and other connective tissue disease subgroups.

Antibodies to the ribonucleoprotein (RNP) component of extractable nuclear antigen were measured in patients with systemic lupus erythematosus (SLE) and other connective tissue subgroups by counterimmunoelectrophoresis. Antibodies to RNP were found in the sera of 32% of patients with a primary diagnosis of SLE, 29% of patients with features of SLE and erosive joint disease, none of 9 scleroderma patients, and in 75% of 8 patients with features of SLE and scleroderma. In the SLE patients overall there was an increased frequency of sclerodactyly and severe Raynaud's phenomenon in the patients with antibodies to RNP but no association of antibodies to RNP was found with the presence of erosive joint disease, Sjögren's syndrome, or the absence of renal disease in these patients.     

Antibodies to retroviral proteins in autoimmune connective tissue disease. Relation to clinical manifestations and ribonucleoprotein autoantibodies.

OBJECTIVE. To study the relationship between antibodies that recognize human retroviral proteins and the presence of clinical features and ribonucleoprotein antibodies in patients with autoimmune connective tissue diseases (CTDs). METHODS. Antibodies against native human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia/lymphoma virus type I, recombinant HIV-1 Nef protein, and ribonucleoprotein antigens were determined by immunoblot of sera from 65 prospectively studied patients with definite or suspected CTDs of autoimmune type. RESULTS. Antibodies to retroviral proteins (ARP), most frequently to HIV Gag proteins p55 and p24, were found in 64% of 22 patients with systemic lupus erythematosus (SLE), in 63% of 8 patients with discoid LE (DLE), in 75% of 8 patients with mixed connective tissue disease (MCTD), and in 26% of 19 individuals with chronic biologically false-positive (CBFP) seroreactions, but not in 8 patients with subacute cutaneous lupus erythematosus. No clear correlation of ARP with antibodies to any specific small nuclear RNP antigen was observed. The most striking finding was that recurrent infections, both in LE patients and in those with CBFP reactions and widespread, acral discoid skin lesions, occurred significantly more often in ARP-positive patients. CONCLUSION. The occurrence of antibodies reacting with human retroviral proteins is associated with severe skin lesions and recurrent infections in SLE, DLE, and MCTD patients, and with a disposition toward developing systemic disease in CBFP reactors.     

Lupus-specific autoantibodies in concomitant human immunodeficiency virus and systemic lupus erythematosus: case report and literature review

OBJECTIVES: To report a case of systemic lupus erythematosus (SLE) in a patient with human immunodeficiency virus (HIV) infection. We also reviewed the medical literature for similar cases to assess the role of "lupus-specific antibodies" in the diagnosis of SLE in the presence of HIV infection. METHODS: We described the presentation, clinical course, and serologic studies of our patient and reviewed the English language medical literature from 1966 to 1999 using MEDLINE with the keywords "SLE," "HIV," "acquired immune deficiency syndrome (AIDS)," and "autoantibodies." RESULTS: Our patient with long-standing HIV infection presented with fever, arthralgias and arthritis, photosensitive rash, oral ulcers, alopecia, headache, pleuritic chest pain, and lymphadenopathy. Laboratory testing showed leukopenia, thrombocytopenia, antibodies against ribonucleoprotein, Smith, and ribosomal-P, as well as immunoglobulin G anticardiolipin antibodies. Review of the literature revealed only 25 cases of concomitant SLE and HIV. In these cases, rheumatologic signs and symptoms were common in HIV and overlapped significantly with SLE. Autoantibodies also occurred frequently in both diseases. CONCLUSIONS: There are very few reported cases of concomitant HIV and SLE. These diseases may be largely mutually exclusive, but distinguishing the two can be difficult because of the high degree of rheumatic complaints and autoantibodies in HIV-positive patients. As illustrated by the patient presented, SLE should be considered in HIV-positive patients with rheumatologic complaints.     

Antibodies to retroviral proteins in autoimmune connective tissue disease. Relation to clinical manifestations and ribonucleoprotein autoantibodies

Objective. To study the relationship between antibodies that recognize human retroviral proteins and the presence of clinical features and ribonucleoprotein antibodies in patients with autoimmune connective tissue diseases (CTDs). Methods. Antibodies against native human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia/lymphoma virus type I, recombinant HIV-1 Nef protein, and ribonucleoprotein antigens were determined by immunoblot of sera from 65 prospectively studied patients with definite or suspected CTDs of autoimmune type. Results. Antibodies to retroviral proteins (ARP), most frequently to HIV Gag proteins p55 and p24, were found in 64% of 22 patients with systemic lupus erythematosus (SLE), in 63% of 8 patients with discoid LE (DLE), in 75% of 8 patients with mixed connective tissue disease (MCTD), and in 26% of 19 individuals with chronic biologically false-positive (CBFP) seroreactions, but not in 8 patients with subacute cutaneous lupus erythematosus. No clear correlation of ARP with antibodies to any specific small nuclear RNP antigen was observed. The most striking finding was that recurrent infections, both in LE patients and in those with CBFP reactions and widespread, acral discoid skin lesions, occurred significantly more often in ARP-positive patients. Conclusion. The occurrence of antibodies reacting with human retroviral proteins is associated with severe skin lesions and recurrent infections in SLE, DLE, and MCTD patients, and with a disposition toward developing systemic disease in CBFP reactors.     

ANA-negative systemic lupus erythematosus.

The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of systemic lupus erythematosus (SLE). Ten patients with clinical signs of disease but persistent negative tests for ANA are examined in this study. Hair fall, Raynaud's phenomenon and recurrent oral ulcers were common in the ANA-negative group. ANA-negative SLE seems to be a subgroup of SLE that has not previously been given adequate attention.     

Extractable nuclear antigens

ENAs are acidic macromolecules extracted from the saline soluble fractions of cells. Twenty different ENAs have been described to date. The antigens are derived from several different sources, and antibodies to these antigens can be detected by a number of different techniques.Antibodies to ENAs usually produce a speckled ANA pattern. The clinician, seeing such a result, will often pursue this by ordering an “ENA” to clarify which antigen-antibody system is responsible for the speckled ANA. Most often, clinical laboratories report results of hemagglutination assays giving the titers of agglutination with and without prior RNase digestion. Antibodies sensitive to RNase have been taken to be the equivalent of anti-RNP, the antibody associated with MCTD. Antibody not sensitive to RNase has often been equated with antibody to the Sm antigen associated with SLE. The failures and abuses of this nomenclature have been discussed in detail.Defining ENAs and the particular anti-ENA antibodies seen in individual patients is of value. From a clinical standpoint, defining these antigen-antibody systems may be helpful for diagnostic and prognostic purposes. From a more basic standpoint, understanding these antigenantibody systems may provide insights into the etiology and pathogenesis of CTDs. To date, only a few of the anti-ENA antibodies discussed above are available for routine clinical use. The extensive review of present information is briefly summarized below.The presence of antibody to RNP correlates with an overlap syndrome, MCTD,^3,12 though long-range studies have shown a progression of PSS-like features.^19,20 These patients, however, seem to have a favorable response to steroids.^3,12,19 Antibodies to Sm and MA are highly specific for SLE.^6–11 While antibodies to Sm may connote a more benign disease with less renal involvement,^8–10 antibodies to MA seem to point to more severe disease.¹¹ The presence of antibodies to PM-1, Mi, and Jo-1 are found mainly in patients with clinical findings of myositis.^24–28 However, they do not correlate with disease activity or severity. Antibodies to Scl-70 are highly specific for PSS.²⁹ Antibodies to SS-A (Ro) are found mainly in patients with SLE and/or the sicca complex,^39–43 and antibodies to SS-B (La or Ha) are present in patients with the sicca complex alone or in association with SLE.^{37–39,41–43} Antibodies to Ro and/or La are directed to cytoplasmic constituents and would account for the presence of clinical SLE in patients with a negative ANA.^37,38,40 They may also be found in a more benign form of SLE.³⁹ Antibodies to RANA (SS-C) are found mainly in patients with RA or RA in combination with SS.^42,44 Thus, the patient with clinical symptoms of a CTD and a speckled ANA pattern or, in limited cases other ANA patterns or a negative ANA, should be evaluated for antibodies to ENA by the HA and ID. Such information can be useful in determining diagnosis and prognosis and expand our understanding of CTDs.     

抗增殖型细胞核抗原抗体在系统性红斑狼疮患者的临床意义

目的:探讨抗增殖型细胞核抗原(PCNA)抗体在系统性红斑狼疮(SLE)患者中的意义及临床相关性.方法:采用间接免疫荧光法(IIF)检测抗PCNA抗体,并用线性免疫印迹法将部分IIF-抗PCNA抗体阳性的患者血清进行特异性抗体检测.结果:抗PCNA抗体阳性患者55例,包括SLE 24例,占43%,未分化结缔组织病(UCT...     

Antibodies in human serum that precipitate ribonuclease P

Sera from certain patients with systemic lupus erythematosus (SLE) and related rheumatic diseases contain antibodies that selectively deplete extracts of HeLa cells of RNase P activity. Most of the sera that recognize RNase P, an endoribonuclease with an essential RNA subunit, also contain antibodies against another small ribonucleoprotein known as the Th antigen. A species of RNA about 400 nucleotides in length is the only RNA species found in common in all immunoprecipitates prepared with anti-RNase P antibodies. The discovery of antibodies against RNase P defines a major class of antibodies produced by patients with autoimmune disease.     

Antinuclear antibodies (ANA): Immunologic and clinical significance

The methods currently used for the detection of ANA have been analyzed, with emphasis on their practical application to the diagnosis of the CTD. The use of the indirect IF-ANA test was recommended as a screening procedure to detect ANA. The need to standardize the technique using a single substrate and fluorescent conjugates with uniform $\text{F}\text{P}$ ratios was stressed. Most importantly, the value of titrating ANA for the diagnosis of the CTD was discussed. ANA titers higher than 1/500 are usually very significant clinically, often found in spontaneous or drug-induced SLE and few other CTD. The immunologic aspects of ANA and their potential value as aids in the diagnosis and management of the CTD were discussed. Anti-nDNA antibodies have been found to have a high degree of specificity for SLE and high titers of these antibodies correlate well with low levels of serum complement and severity of kidney involvement. The spectrum of ANA in the sera from patients with SLE has been expanded with the finding of anti-Sm antibodies which, when detected by gel precipitation with prototype serum, have been found so far only in SLE. Some of these antibodies have been found to have prognostic significance. Patients with MCTD and a group of patients with SLE have high titers of serum ANA with specificity for an RNase-sensitive component of ENA. The group of SLE patients defined by the presence of these antibodies (anti-Mo) have a better prognosis and in general develop only mild nephritis or have no kidney involvement at all. High titers of pure antinucleolar antibodies probably are found almost exclusively in the sera of patients with scleroderma. Some ANA have organ specificity, and GS-ANA have been found in all patients with Felty's syndrome and in a large proportion of patients with RA.One of the great advances in the field has been the recognition that ANA can be induced in the human and in experimental animals by the use of a number of therapeutic agents. Some of these agents can also induce a clinical picture resembling spontaneous SLE, though kidney involvement does not occur or is extremely mild. It is interesting that the whole spectrum of ANA can be found in drug-induced LE except anti-nDNA antibodies which have been associated to the pathogenesis of immune complex nephritis in spontaneous SLE.There is no doubt that research on ANA has contributed a great deal to the understanding of the CTD and will continue to be a valuable tool for the clinician and the investigator.     

Association of psychiatric manifestations with antibodies to ribosomal P proteins in systemic lupus erythematosus

PURPOSE: The goal of this study was to determine whether elevated serum levels of antibodies to ribosomal P proteins (anti-P antibodies) are associated with neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE). Additional experiments examined characteristics of these antibodies that might be associated with pathogenicity. PATIENTS AND METHODS: A large number of serum samples were collected from patients with SLE, control subjects with other rheumatic diseases, and normal individuals. At the time serum samples were obtained, patients with SLE were categorized according to the presence of psychosis, depression, and other manifestations of central nervous system (CNS) involvement. Serum anti-P antibody activity was quantitated by an enzyme-linked immunosorbent assay utilizing a synthetic peptide corresponding to the major P protein epitope. RESULTS: In a group of 79 normal individuals, mean (+/- SE) IgG anti-P activity was 0.01 +/- 0.003 and no individuals had values greater than 3 SD above the mean. Similar results were obtained measuring IgM anti-P activity. Normal levels were found in all sera from 21 patients with rheumatoid arthritis. Of 119 patients demonstrating various patterns of antinuclear and anticytoplasmic antibody activity, elevated anti-P levels were found only in patients with SLE. Overall, 19% of 269 patients with SLE demonstrated elevated levels of IgG or IgM anti-P antibodies, including 14% of 187 patients without and 29% of 82 patients with neuropsychiatric manifestations. The frequency of positive test results varied greatly depending on the nature of the CNS involvement. The frequency in patients with severe depression (n = 8) and psychosis (n = 29) was 88% and 45%, respectively, compared with only 9% in patients with nonpsychiatric neurologic disease (n = 45). For the entire SLE group, the odds ratio for the association of anti-P antibodies and severe psychiatric manifestations was 7.63 with a 95% confidence interval of 3.61 to 16.14. In a review of 187 patients with SLE originally classified as not having severe psychiatric disease, seven of 10 patients being treated with antidepressant medications had elevated levels of anti-P antibodies. In serial studies, the serum level of anti-P antibodies appeared to correlate with the activity of psychiatric disease and did not correlate with the activity of other manifestations of SLE. Anti-P antibodies in nearly all patients were IgG and directed primarily to the C-terminal 11 amino acids of the P protein. No difference in these characteristics was observed when patients with and without psychiatric manifestations were compared. Paired serum and cerebrospinal fluid (CSF) samples were also obtained from eight patients with active neuropsychiatric disease. Even when expressed as a fraction of the total IgG present, anti-P activity was markedly lower in CSF than in serum. CONCLUSIONS: Elevated levels of autoantibodies to the C-terminal region of ribosomal P proteins appear to be a specific marker for SLE, and are associated with both severe depression and psychosis in this disease. This assay is easily reproducible and may help distinguish SLE-induced psychiatric disease from that caused by other processes.     

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.     

Nine-year's follow up on the appearance of autoantibodies in a child with idiopathic thrombocytopenic purpura subsequently developing lupus with central nervous system manifestations]

We describe a 23-year-old female who developed SLE 9 years after asymptomatic idiopathic thrombocytopenic purpura (ITP) with positive antinuclear antibody (ANA). Although the platelet count was normal before the onset of SLE, the titer of ANA was gradually increased and also autoantibodies, including antibodies to SS-A/Ro, single-stranded DNA (ss-DNA) and nuclear ribonucleoprotein (RNP) changed to positive. At 23 years of age, the patient was admitted to our hospital because of fever, butterfly rash and polyarthritis. Anti double-strand DNA (ds-DNA) antibody and anti Smith antigen (Sm) antibody were positive and the platelet count and titer of complements were decreased. The patient was diagnosed as SLE and treated with 60 mg/day of prednisolone. Despite steroid therapy, psychiatric symptoms appeared. Additional treatments with steroid pulse therapy and double filtration plasmaphresis resulted in the improvement of SLE including the central nervous system manifestations. This case suggested that increased titer of ANA and the appearance of antibodies to SS-A, ss-DNA, RNP, ds-DNA and Sm in ITP patients predict the development of SLE. Routine checkup of autoantibodies is needed to manage ITP with positive ANA.     

Clinical characteristics of patients with rheumatic disorders who possess antibodies against ribonucleoprotein particles

IgG was purified from 91 serum samples obtained from patients with systemic rheumatic diseases and examined for the presence of antinuclear antibodies reactive with small ribonucleoprotein (RNP) complexes. Antibody specificity was determined by autoradiographic detection of ³²P labeled RNA which had been separated by polyacrylamide gel electrophoresis. This RNA was extracted from immune complexes formed by adding purified IgG to a homogenate of ³²P labeled HeLa cells. Anti-RNP antibodies were detected in 70% of these samples. Specific antibodies detected were anti-(U1)-RNP (35%), anti-Sm (30%), anti-Ro (24%), and anti-La (10%). Other antibodies (9%) were reactive with structures containing 5S and 5.8S RNA or 4S RNA. There was a significant relationship between the presence of anti-RNP antibodies in patients with systemic lupus erythematosus (SLE) (78%) as opposed to their presence in patients with non-SLE rheumatic disorders (45%). However, taken individually, anti-Ro was the only antibody whose presence in SLE patients (30%) was significantly greater than its presence in non-SLE patients (5%). Vasculitis was the only clinical manifestation found to correlate with the presence of a particular antibody, anti-(U1)RNP. There is some suggestion of a racial distribution of antibody types.     

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.