U1-RNP Antibodies Research Articles

Anticorps antiprotéines ribosomales P et lupus systémique

Autoantibodies to ribosomal P proteins are directed against three ribosomal phosphoproteins named P0, P1 and P2. They are considered a specific marker of systemic lupus erythematosus (SLE) and various reports have shown an association between these autoantibodies and neuropsychiatic manifestations of SLE. The aim of this study was to determine the frequency and clinical associations of anti ribosomal P antibodies in Tunisian patients with SLE. Methods. One hundred Tunisian patients of whom sera were collected at the immunology laboratory in the Charles Nicolle hospital in Tunis in a period from January 1998 to December 2000 have been studied. Results. Anti ribosomal P antibodies were detected using a line immunoassay (Innogenetics) in which the autoantigen is a synthetic peptide shared by the ribosomal phosphoproteins. Twenty two patients were positive for anti ribosomal (22%). No significant clinical association was found in patients with anti ribosomal antibodies. Conclusion. We have found a strong association between anti ribosomal P and anti Sm and anti U1 RNP antibodies. This association was reported previously but its significance is unclear.

The appearance of U1 RNP antibody specificities in sequential autoimmune human antisera follows a characteristic order that implicates the U1–70 kd and B′/B proteins as predominant U1 RNP immunogens

The appearance of U1 RNP antibody specificities in sequential autoimmune human antisera follows a characteristic order that implicates the U1–70 kd and B′/B proteins as predominant U1 RNP immunogens

The appearance of U1 RNP antibody specificities in sequential autoimmune human antisera follows a characteristic order that implicates the U1-70 kd and B'/B proteins as predominant U1 RNP immunogens.

To observe the order of development of anti-U1 RNP peptide antibodies in humans. Immunoblots against Jurkat cell lysates were performed on 5,882 serum samples from 3,668 patients referred on clinical grounds for RNP antibody testing to a reference laboratory between 1989 and 1999. In patients from whom multiple samples were drawn, we determined the order in which IgG antibodies to the U1 RNP peptides A, B'/B, C, D, and 70 kd appeared. One hundred sixty-three patients with serial samples were identified in whom antibodies to at least one U1 RNP peptide initially were not present but later appeared. The first RNP antibodies to appear were most often directed against the 70 kd and B'/B peptides (P < 0.01). Antibodies to the A and C peptides usually developed after other RNP peptide antibodies, and antibodies to D often emerged only after immunity to multiple other U1 RNP proteins had appeared. B'/B, but not 70 kd, was a frequent early target of spreading after initial immunity to other RNP peptides. Orderly patterns of emergence of U1 RNP peptide antibodies appear to exist in humans. Two peptides, 70 kd and B'/B, show characteristics of early immunogens in the development of human RNP immunity.

Development of the antinuclear and anticytoplasmic antibody consensus panel by the Association of Medical Laboratory Immunologists.

The Association of Medical Laboratory Immunologists (AMLI) have developed a panel of antinuclear and anticytoplasmic antibody consensus sera that can be useful for enzyme immunoassay (EIA), Ouchterlony, and immunofluorescence assay methods. It was developed to assist in the evaluation of newly available EIA methods for the detection of autoantibodies. The panel of sera was evaluated in several clinical laboratories and a large number of laboratories owned by manufacturers of clinical autoantibody testing kits. The majority of sera performed well for the EIAs in both the clinical laboratories and the manufacturers' laboratories, but some samples had discrepant results. A major source of discrepancy is the current inability of the EIA results to be directly compared in a quantitative way as no standardization exists. The evaluation demonstrated lower sensitivity of detection by the Ouchterlony method. The limited evaluation of the sera with immunoblotting and Western blotting did not show good agreement with other methods. Further work must be done to standardize blotting methods prior to their use in routine clinical testing. The sera are now available to vendors and clinical laboratories for use in the detection of SS-A, SS-B, Sm, U1-RNP, Scl-70, Jo-1, double-stranded DNA, and centromere antibodies. The availability of the consensus sera will help evaluate and improve the EIA methods currently being used.

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies

To elucidate the roles of HLA genes in the clinical presentation of patients with connective tissue disease and serum anti-U1 small nuclear RNP antibody. HLA class I antigens and HLA class II alleles were determined in 43 Japanese patients with anti-U1 RNP antibody alone, by microcytotoxicity testing and DNA typing, respectively. Prospectively recorded clinical and laboratory features were analyzed in relation to HLA class I and class II types. DQB1*0303 was associated with lupus-related symptoms including fever, malar rash, oral ulcers, hypocomplementemia, and high-titer anti-double-stranded DNA antibody. Other HLA-clinical associations included DR2 with pleuritis, DR4 with hand swelling, and DRB1*0405 with arthritis. These HLA-clinical associations explain, in part, the heterogeneous clinical presentation in patients with anti-U1 RNP antibody.

Major histocompatibility complex class ii gene associations with anti–u1 small nuclear ribonucleoprotein antibody relationship to immunoreactivity with individual constituent proteins

To better define immunogenetic associations with the anti-U1 ribonucleoprotein (U1 RNP) autoantibody response. HLA class II alleles were determined by genotyping in 49 Japanese rheumatic disease patients with anti-U1 RNP antibody and 43 race-matched healthy controls. Immunoreactivities to U1 RNP constituent proteins (70K, A, B/B', and C) were detected by immunoblots using purified HeLa cell Sm antigen, and antibody titer was determined by passive hemagglutination assay. DQB1*0302 was significantly more frequent in anti-U1 RNP-positive patients than in controls (43% versus 14%; odds ratio [OR] = 4.6, corrected P = 0.03). All anti-U1 RNP-positive patients had either a DQB1*0601, *0602, *0301, *0302, or *0303 allele, which share tyrosine at position 30, and the amino acid sequence Thr, Arg, Ala, Glu, Leu, Asp, and Thr at positions 71-77 in the DQB1 beta 1 domain. In contrast, one of these alleles was found in 81% of the controls (OR = 24, P = 0.002). In addition, anti-U1 RNP antibody was associated with unique DQB1*0302; DRB1*0401 haplotype. Anti-70K reactivity and antibody titer were positively associated with a basic amino acid residue, arginine or histidine, at position 13 (DR2 or DR4) and were negatively associated with the amino acid sequence Ile, Leu, Glu, and Asp at positions 67-70, which was present in some of the DR5-, DR6-, and DR8-associated alleles, in the DRB1 beta 1 domain. Anti-C reactivity was strongly associated with DR2, particularly with DRB1*1502. The several shared epitopes located on HLA-DRB1 and DQB1 genes control the anti-U1 RNP autoantibody response.

Overlapping syndromes, undifferentiated connective tissue disease, and other fibrosing conditions.

Connective tissue diseases (CTDs) frequently present as undifferentiated disorders that may or may not develop into one of the well defined CTDs. The natural evolution of the early undifferentiated CTDs is not well known. Some years ago a cooperative study was started on 410 patients with early CTD; within this group, 48 patients had early scleroderma. Raynaud's phenomenon has been recognized as an early sign of CTD. Several studies on Raynaud's phenomenon patients have shown that abnormal nailfold capillary patterns have prognostic significance for evolution to a CTD, particularly scleroderma. Mixed connective tissue disease (MCTD) is the prototype of an overlap syndrome. The relevance of defining MCTD as a separate disease entity has been challenged. Follow-up studies show that many patients originally diagnosed with MCTD develop a definite CTD, particularly scleroderma or systemic lupus erythematosus, within a few years. In patients with MCTD, primary pulmonary hypertension is an important cause of death. This condition seems to be associated with anticardiolipin antibodies. A number of case reports suggest that immunosuppressive treatment is of benefit in this almost always fatal condition. The main reason for describing MCTD as a separate entity is its association with antibodies to U1-RNP. Recent studies have suggested that the production of anti-U1-RNP is an antigen-driven process, but the nature of the trigger for its production has not been elucidated. Retroviral proteins do not appear to be involved. Antibodies to the protein part of the U1-RNP complex and antibodies to the RNA component have been described. Levels of anti-RNA antibodies seem to parallel disease activity in MCTD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical significance of IgG subclasses of anti-Sm and U1 ribonucleoprotein antibodies in patients with systemic lupus erythematosus and mixed connective tissue disease

IgG subclasses of anti-Sm and anti-U1 ribonucleoprotein (U1 RNP) antibodies were determined using a new clone of the anti-IgG2 antibody (HG2-56F). Although the predominance of IgG1 coincided with previous reports, IgG2 anti-Sm and U1 RNP antibodies were detected in numerous patients. IgG3 anti-Sm antibody significantly correlates with joint involvement and a high titer of anti-DNA antibody. On the other hand, IgG4 anti-U1 RNP antibody significantly correlated with esophageal dilation and muscular involvement. These results may suggest that some IgG subclasses are related to a specific clinical feature or manifestation.