Autoantibodies to the core proteins of hnRNPs

Dangli, Amalia; Guialis, Apostolia; Vretou, Evangelia; Sékeris, Constantin E.

doi:10.1016/0014-5793(88)80714-2

Cited by 14 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Heterogeneous nuclear ribonucleoproteins (hnRNPs) are among the most abundant proteins in the eukaryotic cell nucleus and play a direct role in several aspects of RNA life including splicing, export of mature RNAs and translation [18,19]. Autoantibodies directed against spliceosomal hnRNPs, hnRNP A, B, C and R were found to be related to rheumatoid arthritis, SLE, and mixed-connective tissue disease [20][21][22][23]. Antibodies directed to hnRNP I (polypyrimidine tract-binding protein), a homolog of hnRNP L, were detected in the sera of systemic sclerosis patients [24].…”

Section: Discussionmentioning

confidence: 99%

Proteomics‐based identification of autoantibodies in the sera of healthy Chinese individuals from Beijing

Zhao

et al. 2006

Proteomics

View full text Add to dashboard Cite

The identification of panels of tumor antigens that elicit an antibody response may have utility in cancer screening, diagnosis and in establishing prognosis. However, autoantibodies normally exist in sera of healthy individuals and are enormously diversified. To explore the reservoir of autoantibody in healthy population, we performed a proteomics investigation of autoantibody profiles in the sera of 36 healthy Chinese individuals from Beijing, which may provide valuable reference information to the identification of disease-specific autoantibodies. The results showed that autoantibody profiles varied individually, but some autoantibodies were identified at a high frequency in the healthy population. The autoantibodies against alpha-enolase and those against heterogeneous nuclear ribonucleoprotein L were positive in more than 50% of the sera samples. The autoantibodies identified in more than 20% of samples included those against annexin II, F-actin capping protein beta subunit and calreticulin. Some of these autoantibodies have been previously reported to be involved in autoimmune conditions and cancers. Autoantibodies in the healthy population are important as a foundation from which disease-specific autoantibodies can be defined. Thus our report on autoantibodies in healthy individuals may be useful as a reference for defining new autoantibody biomarkers.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteomics‐based identification of autoantibodies in the sera of healthy Chinese individuals from Beijing

Zhao

et al. 2006

Proteomics

View full text Add to dashboard Cite

show abstract

“…Thus, Abs to Sm and U1 snRNP Ags were described already many years ago to occur in up to 50% of the patients. More recently, Abs to the spliceosome-associated hnRNPs A1 and A2/B1 were found in SLE patients but also in other rheumatic autoimmune disorders, particularly in RA (11)(12)(13)(14)(15)(16). To study the pathological significance of the anti-hnRNP autoimmunity in SLE, we investigated several murine models for the presence of anti-A2/B1 Abs.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent studies showed hnRNPs A/B to form the major targets of these Abs, particularly hnRNP A2/B1 (11)(12)(13)(14)(15). Although anti-A2/B1 Abs are also present in SLE and MCTD, they might represent an important marker Ab for RA because Abs associated with SLE and/or MCTD, such as Abs to dsDNA and U1-small nuclear ribonucleoproteins (snRNPs), are absent in RA.…”

mentioning

confidence: 99%

B and T Cell Responses to the Spliceosomal Heterogeneous Nuclear Ribonucleoproteins A2 and B1 in Normal and Lupus Mice

Dumortier

Monneaux

Jahn‐Schmid

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Autoantibodies directed against spliceosomal heterogeneous nuclear ribonucleoproteins (hnRNPs) are a typical feature of rheumatoid arthritis, systemic lupus erythematosus, and mixed-connective tissue disease. With the aim of investigating a potential pathogenic role of these Abs, we have studied the Ab response to A2/B1 hnRNPs in different murine models of lupus. The specificity of anti-A2/B1 Abs was tested with a series of 14 overlapping synthetic peptides covering the region 1–206 of A2 that contains most of the epitopes recognized by patients’ Abs. A major epitope recognized very early during the course of the disease by Abs from most of MRL lpr/lpr mice but not from other lupus mice and from mice of different MHC haplotypes immunized against B1 was identified in residues 50–70. This peptide contains a highly conserved sequence RGFGFVTF also present in other hnRNPs and small nuclear ribonucleoproteins. Abs reacting with a second A2 epitope identified in residues 35–55 were detectable several weeks later, suggesting an intramolecular B cell epitope spreading during the course of the disease. We identified several T cell epitopes within the region 35–175 that generated an effective Th cell response with IL-2 and IFN-γ secretion in nonautoimmune CBA/J mice sharing the same MHC haplotype H-2k as MRL/lpr mice. None of the peptides stimulated T cells primed in vivo with B1. Because Abs to peptide 50–70 were detected significantly earlier than Abs reacting with other A2 peptides and the protein itself, it is possible that within the protein, this segment contains residues playing an initiator role in the induction of the anti-A2/B1 and antispliceosome Ab response.

show abstract

“…In sera containing both anti-Al and anti-A2/RA33 antibodies (5 8), cross-reactivity between the two antibod ies was generally observed [19]. pared to central and West European patients, the prevalence was found to be very low in RA patients from Finland [24] and Greece [25] and elevated in non-Caucasian patients with SLE [26].…”

Section: Occurrence and Disease Associationmentioning

confidence: 99%

Autoantibodies to the A/B Proteins of the Heterogeneous Nuclear Ribonucleoprotein Complex: Novel Tools for the Diagnosis of Rheumatic Diseases

Steiner

Skriner

Smolen³

1996

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Heterogeneous nuclear ribonucleoprotein (hnRNP) complexes are major constituents of the spliceosome. They are composed of approximately 30 different proteins which can bind to nascent pre-mRNA. Among these, the hnRNP-A/B proteins form a subgroup of highly related proteins: their N-terminal halves consist of two adjacent RNA-binding domains, whereas the C-terminal halves contain almost 50% glycine residues. These proteins represent a group of novel au-toantigens which are targeted by autoantibodies from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD): thus, anti-A2/RA33 autoantibodies target the hnRNP proteins A2, B1, B2 (the ‘RA33 complex’), and anti-A1 autoantibodies are directed to the hnRNP proteins A1 and A1b. In SLE, anti-hnRNP-A/B antibodies frequently occur together with antibodies to two other spliceosome-associated antigens, Ul small nuclear RNP (U1-snRNP) and Sm. Epitope-mapping studies have revealed that the major antibody binding sites are located in the RNA-binding regions. Furthermore, there is some indication of disease-specific epitope recognition. Studies in animal models have demonstrated the presence of anti-hnRNP-A/B antibodies in several lupus-prone mouse strains. Thus, autoantibodies to the spliceosomal hnRNP-A/B proteins are a common feature of RA, SLE, and MCTD. However, these diseases differ in their reactivities to other spliceosomal components, such as U1-snRNP and Sm antigens. Therefore, anti-hnRNP-A/B autoantibodies are not only valuable diagnostic markers but may also allow additional insights into the pathogenetic mechanisms of rheumatic autoimmune diseases.

show abstract

Autoantibodies to the core proteins of hnRNPs

Cited by 14 publications

References 32 publications

Proteomics‐based identification of autoantibodies in the sera of healthy Chinese individuals from Beijing

Proteomics‐based identification of autoantibodies in the sera of healthy Chinese individuals from Beijing

B and T Cell Responses to the Spliceosomal Heterogeneous Nuclear Ribonucleoproteins A2 and B1 in Normal and Lupus Mice

Autoantibodies to the A/B Proteins of the Heterogeneous Nuclear Ribonucleoprotein Complex: Novel Tools for the Diagnosis of Rheumatic Diseases

Contact Info

Product

Resources

About