Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical and laboratory features of 32 patients with anti-PM-Scl were studied. Patients with this rare autoantibody suffered from a homogenous overlap connective tissue disease defined by Raynaud phenomenon (32/32), features of scleroderma (31/32), arthritis (31/32, erosive in 9/32), myositis (28/32), lung restriction (25/32), calcinosis (15/32), and sicca (11/32). Significant renal and neurologic involvement was uncommon. All patients examined (22/22) had HLA-DR3, and 50% of these patients were homozygous. Our patients responded favorably to moderate immunosuppression and, with therapy, the disease generally has a good prognosis; over 50% of our series (17/32) remained well on minimal or no immunosuppression after a median follow-up of 8 years.
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PMID:The clinical and immunogenetic features of patients with autoantibodies to the nucleolar antigen PM-Scl. 143 28

Fourteen patients with childhood scleromyositis followed from 1 to more than 10 years experienced concomitant sclerodermoid and dermatomyositis features, variably expressed at one time or another during the course of the disease. The most characteristic features were myalgia-myositis, arthralgia-arthritis, puffy, atrophic, sclerotic fingers, and Raynaud's phenomenon. This overlap syndrome was the most frequent sclerodermoid condition in children, differing from both systemic scleroderma and dermatomyositis. The course of the disease was protracted and rather benign, and PM-Scl antibody was an important diagnostic and prognostic marker. We present criteria for diagnosis of scleromyositis and its differentiation from systemic scleroderma, dermatomyositis, and Sharp overlap syndrome.
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PMID:Childhood scleromyositis: an overlap syndrome associated with PM-Scl antibody. 190 68

In 1986, we diagnosed and treated 4 patients, all members of 1 rural family, who presented simultaneously with a polymyositis-like syndrome, anticytoplasmic antibodies (on HEp-2 cells), and precipitating antibodies of anti-Jo-1 and anti-PM-Scl specificities. Serum samples from these patients reacted by immunodiffusion against serum from a rodent that had been caught in the patients' house. The precipitin line showed complete immunologic identity with anti-Jo-1. To study the specificity of this serum-serum reaction, 2 mice (Mus musculus) and 1 rat (Rattus rattus) from the neighboring areas of the patients' house were caught and killed. Sections of the liver, kidney, spleen, and skeletal muscle were processed for histopathologic examination and for direct and indirect immunofluorescence studies of the patients' sera. The rodents' sera were tested by immunodiffusion against serum samples from 25 patients with systemic lupus erythematosus, 11 with rheumatoid arthritis, 6 with mixed connective tissue disease, and 11 with various other rheumatic diseases, as well as 16 healthy controls. A serum-serum precipitin reaction was noted between the rodents' sera and sera from 2 of the patients with polymyositis-like syndrome. A distinct, but weaker, reaction was found with 2 lupus patients' sera (8%), and with 1 healthy control serum (6%). The rodents' sera were antinuclear antibody positive by indirect immunofluorescence on HEp-2 cells. These results, suggest that some rodents could be carriers of an as-yet-unknown transmissible agent that, in susceptible individuals, induces clinical and serologic manifestations similar to those of polymyositis.
Arthritis Rheum 1991 Jun
PMID:Acute familial myositis with a common autoimmune response. 205 20

Immunofluorescence on rat liver sections was used to select high-titer antinucleolar antibodies (ANoA) in the sera of patients with systemic sclerosis (scleroderma). In 646 patients, 53 ANoA sera (8%) were identified, and of these, 46 were available in sufficient quantities for further analysis. The complex of RNA polymerase I was immunoprecipitated by 7 sera (15%), which uniformly produced punctate nucleolar staining. The PM-Scl antigen, a particle consisting of 11 polypeptides, was immunoprecipitated by 8 sera (17%), all of which displayed homogeneous nucleolar staining. A 34-kd nucleolar protein (fibrillarin) of the U3 RNP complex was positive in immunoblotting of 22 sera (48%), which characteristically produced clumpy nucleolar staining. Antibodies against RNA polymerase I were associated with diffuse scleroderma of short duration, which was characterized by a high prevalence of internal organ involvement, including renal crisis. Anti-U3 RNP antibodies had a high prevalence in men with significantly less joint involvement, compared with ANoA-negative patients. Anti-PM-Scl antibodies identified a group of scleroderma patients with a high prevalence of concomitant myositis and renal involvement.
Arthritis Rheum 1988 Apr
PMID:Correlates between autoantibodies to nucleolar antigens and clinical features in patients with systemic sclerosis (scleroderma). 245 21

Immune disorders are characterized by development of autoantibodies. Autoantibodies, particularly antinuclear antibodies, are detected in the majority of patients with connective tissue diseases such as systemic lupus erythematosus and scleroderma. Recent reports have described persons with silicone implants who have developed scleroderma and systemic lupus erythematosus. Since autoantibodies are suspected to play an important role in the pathogenesis of the connective tissue disease, the nature of the autoantibodies produced in patients with silicone-associated rheumatic disease is important to understand. A review of the English literature and abstracts from the 1992 American College of Rheumatology meeting showed that immunofluorescent testing for antinuclear antibody was positive in a wide range (7% to 68%) of patients with silicone implants. When examining only those patients with silicone implants and clinical evidence of connective tissue disease, the proportion of patients with a positive immunofluorescent test was less than commonly found in a series of patients with idiopathic connective tissue disease. Sensitive testing by Western blot technique revealed autoantibodies in 10% of patients with silicone implants and negative immunofluorescent test results. Patients with silicone implants and scleroderma-like illness were characterized by anticentromere and anti-PM-Scl antibodies, whereas patients with silicone implants and SLE or undifferentiated connective tissue disease were characterized by antibodies to small nuclear ribonucleoproteins, specifically B'/B polypeptide. In addition, antibodies to a high molecular weight protein have been discovered by Western blot in more than 50% of persons with silicone implants. Differences in autoantibody production between patients with silicone-associated rheumatic disease and patients with idiopathic rheumatic disease may be a distinguishing feature. Further characterization of these autoantibodies is needed.
Semin Arthritis Rheum 1994 Aug
PMID:Autoantibodies in patients with silicone implants. 780 Nov 40

Evidence of autoimmune muscle injury and of systemic autoimmunity is seen in PM and DM. In typical PM, a cell-mediated attack on muscle fibers by CD8+ cytotoxic T cells predominates, directed at an unknown antigen. In DM, vascular injury is prominent, with loss of muscle capillaries and ischemic muscle damage, apparently mediated by local complement activation in small muscle vessels. Although humoral immunity seems more important in the pathogenesis of DM, serum autoantibodies are commonly found in both forms. About one third of patients have MSAs, whereas others have less specific antibodies such as anti-U1RNP, often associated with overlap syndromes involving myositis. MSAs are mutually exclusive and define characteristic clinical subgroups. Antibodies to five of the aminoacyl-tRNA synthetases are each associated with an "antisynthetase syndrome" marked by myositis, ILD, arthritis, and other features, but individual patients have only a single antisynthetase. Rare autoantibodies to certain translation factors may be associated with a similar syndrome. Anti-SRP is commonly associated with severe, acute, resistant myositis, whereas anti-Mi-2, the only MSA directed at a nuclear protein, is specifically associated with DM. Patients with anti-PM-Scl commonly have an overlap syndrome of PM/DM and SSc. Recent studies have recognized other antibodies in PM and DM, including antibody to endothelial cells, heat shock proteins, and, in a high proportion of patients, a 56-kd component of a ribonucleoprotein particle. The MSAs and their antigens are being characterized in detail. To date, data suggest similarity of predominant epitopes between different patients and a tendency toward conformational epitopes. It is not known if the recognized autoantibodies participate in tissue injury or pathogenetic processes, but production of the MSAs appears to be linked to etiologic factors and can be a clue to understanding the disease. Although these autoimmune responses are becoming better defined, the inciting events leading to generation of these responses and development of PM and DM remain unknown.
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PMID:Immune manifestations of inflammatory muscle disease. 785 26

The most common scleroderma overlap syndromes are mixed connective tissue disease (MCTD), scleromyositis and synthetase syndrome. There is controversy concerning MCTD as a separate entity due to heterogeneous clinical manifestations, not infrequent transformation into definite CTD and various classification criteria. Our study of 94 adult patients and 20 children, classified according to the criteria of Alarcon-Segovia, and especially a 5, 9-year follow-up showed transformation into SLE or SSc in over 20% of patients, less frequently than reported by others, whereas over half of the cases remained undifferentiated CTD. In several cases ARA criteria for both SSc and SLE were fulfilled, and there is no consensus whether such cases should be recognized as coexistence of both definite diseases or as MCTD. High titers of U1 RNP antibodies to 70 kD epitope were invariably present, whereas, by transformation into distinctive CTD there appeared, in addition, antibodies characteristic of these CTD. Of 108 cases positive for PM-Scl antibody, 83% were associated with scleromyositis. This scleroderma overlap syndrome differed from MCTD by coexistent features of dermatomyositis (myalgia, myositis, Gottron sign, heliotrope rash, calcinosis) with no component of SLE, characteristic of MCTD. The course was also chronic and rather benign, as in MCTD, and all cases responded to low or moderate doses of corticosteroids. A not infrequent complication was deforming arthritis of the hands. Our immunogenetic study showed an association of cases positive for PM-Scl antibody with HLA-DQA1x0501 alleles in 100% and with HLA-DRB1x0301 in 94% of cases. Synthetase syndrome, associated with anti-histidyl-tRNA synthetase antibodies, studied in 29 patients with myositis and interstitial lung disease (ILD), only in single cases had scleroderma-like features. These cases differed from SSc by acute onset with fever, and by response to moderate doses of corticosteroids. We also studied overlap of localized scleroderma with other CTD: 21 cases of progressive facial hemiatrophy and linear scleroderma, and 55 (39.5%) of atrophoderma Pasini-Pierini (APP) and morphea. As in other autoimmune disorders, two or more connective tissue diseases (CTD) may develop concurrently or sequentially in the same patient. In such overlap syndromes ARA criteria must be fulfilled for each of the disease, and the clinical presentation has features of both. However more frequently overlap syndromes only combine some manifestations of more than one CTD, and present a highly heterogeneous group of disorders with prevailing clinical features of SSc.
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PMID:Scleroderma overlap syndromes. 1059 27

Scleroderma (systemic sclerosis) is associated with several autoantibodies, each of which is useful in the diagnosis of affected patients and in determining their prognosis. Anti-centromere antibodies (ACA) and anti-Scl-70 antibodies are very useful in distinguishing patients with systemic sclerosis (SSc) from healthy controls, from patients with other connective tissue disease, and from unaffected family members. Whereas ACA often predict a limited skin involvement and the absence of pulmonary involvement, the presence of anti-Scl-70 antibodies increases the risk for diffuse skin involvement and scleroderma lung disease. Anti-fibrillarin autoantibodies (which share significant serologic overlap with anti-U3-ribonucleoprotein antibodies) and anti-RNA-polymerase autoantibodies occur less frequently and are also predictive of diffuse skin involvement and systemic disease. Anti-Th/To and PM-Scl, in contrast, are associated with limited skin disease, but anti-Th/To might be a marker for the development of pulmonary hypertension. Other autoantibodies against extractable nuclear antigens have less specificity for SSc, including anti-Ro, which is a risk factor for sicca symptoms in patients with SSc, and anti-U1-ribonucleoprotein, which in high titer is seen in patients with SSc/systemic lupus erythematosus/polymyositis overlap syndromes. Limited reports of other autoantibodies (anti-Ku, antiphospholipid) have not established them as being clinically useful in following patients with SSc.
Arthritis Res Ther 2003
PMID:The clinical relevance of autoantibodies in scleroderma. 1271 48

The objective of this study was to determine the prevalence, mutual associations, clinical manifestations, and diagnoses associated with serum autoantibodies, as detected using recently available immunoassays, in patients with autoimmune myositis (AIM). Sera and clinical data were collected from 100 patients with AIM followed longitudinally. Sera were screened cross-sectionally for 21 autoantibodies by multiplex addressable laser bead immunoassay, line blot immunoassay, immunoprecipitation of in vitro translated recombinant protein, protein A assisted immunoprecipitation, and enzyme-linked immunosorbent assay. Diagnoses were determined using the Bohan and Peter classification as well as recently proposed classifications. Relationships between autoantibodies and clinical manifestations were analyzed by multiple logistic regression. One or more autoantibodies encompassing 19 specificities were present in 80% of the patients. The most common autoantibodies were anti-Ro52 (30% of patients), anti-Ku (23%), anti-synthetases (22%), anti-U1RNP (15%), and anti-fibrillarin (14%). In the presence of autoantibodies to Ku, synthetases, U1RNP, fibrillarin, PM-Scl, or scleroderma autoantigens, at least one more autoantibody was detected in the majority of sera and at least two more autoantibodies in over one-third of sera. The largest number of concurrent autoantibodies was six autoantibodies. Overall, 44 distinct combinations of autoantibodies were counted. Most autoantibodies were unrestricted to any AIM diagnostic category. Distinct clinical syndromes and therapeutic responses were associated with anti-Jo-1, anti-fibrillarin, anti-U1RNP, anti-Ro, anti-Ro52, and autoantibodies to scleroderma autoantigens. We conclude that a significant proportion of AIM patients are characterized by complex associations of autoantibodies. Certain myositis autoantibodies are markers for distinct overlap syndromes and predict therapeutic outcomes. The ultimate clinical features, disease course, and response to therapy in a given AIM patient may be linked to the particular set of associated autoantibodies. These results provide a rationale for patient profiling and its application to therapeutics, because it cannot be assumed that the B-cell response is the same even in the majority of patients in a given diagnostic category.
Arthritis Res Ther 2007
PMID:Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes. 1768 95

Abstract Evidence of the involvement of systemic autoimmunity has been observed in polymyositis/dermatomyositis (PM/DM). Autoantibodies directed against various cellular constituents have been detected in most patients with PM/DM, and about one-third of patients have autoantibodies (myositis-specific antibodies: MSAs) that are found specifically in myositis patients. These autoantibodies are closely associated with a characteristic clinical subgroup, and therefore help in establishing the correct diagnosis, classifying the myositis patients in a homogeneous subset, and facilitating the clinical and treatment follow-up. Autoantibodies to six of the aminoacyl tRNA synthetases are each associated with a similar syndrome marked by myositis, interstitial lung disease, arthritis, and other features constituting an "antisynthetase syndrome." Antibodies to other cytoplasmic antigens that are involved in protein synthesis or translation factors are seen in a small proportion of patients. Antisignal recognition particles are associated with severe, refractory myositis that differs significantly from antisynthetase syndrome. Antibodies to the nuclear antigen are specifically seen in patietnts with DM. Several autoantibodies, including anti-U1 RNP, anti-U2 RNP, anti-Ku, and anti-PM-Scl, have been associated with scleroderma-PM overlap. In recent years, these MSAs and their antigens have been characterized using molecular biology approaches. It is not known if the MSAs are involved in tissue injury or the pathogenesis of PM/DM. However, an understanding of the production mechanisms of these autoantibodies can provide insight into the etiology of this disorder.
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PMID:Humoral aspects of polymyositis/dermatomyositis. 2438 29


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