RA33
Encyclopedia
RA33, also known as heterogeneous nuclear ribonucleoprotein A2/B1 is an autoantigen in human autoimmune diseases.
In 1989, a novel class of autoantibodies were detected in sera of patients with rheumatoid arthritis
(RA) which were directed to a protein with an estimated molecular mass of approximately 33 kDa contained in nuclear extracts from HeLa
cells. The antigen was therefore given the name RA33. Protein sequencing of highly purified RA33 revealed that it was identical to the hetergoneous nuclear ribonucleoprotein A2 (hnRPA2B1
).
Nowadays, the name anti-RA33 defines autoantibodies that are directed to hnRNP-A2 and its splice variant hnRNP-B1. Anti-RA33 occur in approximately 30-35% of patients with RA, in 20-25% of patients with systemic lupus erythematosus
and in 35-40% of patients with mixed connective tissue disease
, being rare or absent in other arthritic conditions with a non-autoimmune etiology. Anti-RA33 can be easily detected by immunoblotting employing crude nuclear extracts or the recombinant antigen. Fo routine diagnostics also ELISA
can be employed which is somewhat less sensitive than immunoblotting. The use of indirect immunofluorescence is of limited usefulness for detecting anti-RA33.
The pathogenic role of anti-RA33 is not fully understood. Anti-RA33 and T cells directed against RA33, that can be found in about 60% of RA patients might contribute to autoimmune inflammation by immune complex
formation or by virtue of secretion of cytokines that may initiate and drive the pathogenic process. Of note, anti-RA33 are detectable already in the earliest disease stage of RA or even years before the onset of actual clinical disease. The positive predictive value
of anti-RA33 is 74%. However, anti-RA33 are not associated with bone erosions or disease activity. In the absence of rheumatoid factor
and anti-citrullinated protein antibody
they are associated with a milder disease course of RA rather.
In 1989, a novel class of autoantibodies were detected in sera of patients with rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
(RA) which were directed to a protein with an estimated molecular mass of approximately 33 kDa contained in nuclear extracts from HeLa
HeLa
A HeLa cell is a cell type in an immortal cell line used in scientific research. It is the oldest and most commonly used human cell line. The line was derived from cervical cancer cells taken on February 8, 1951 from Henrietta Lacks, a patient who eventually died of her cancer on October 4, 1951...
cells. The antigen was therefore given the name RA33. Protein sequencing of highly purified RA33 revealed that it was identical to the hetergoneous nuclear ribonucleoprotein A2 (hnRPA2B1
HNRPA2B1
Heterogeneous nuclear ribonucleoproteins A2/B1 is a protein that in humans is encoded by the HNRNPA2B1 gene.HnRNPA2B1 is an autoantigen in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and mixed connective tissue disease...
).
Nowadays, the name anti-RA33 defines autoantibodies that are directed to hnRNP-A2 and its splice variant hnRNP-B1. Anti-RA33 occur in approximately 30-35% of patients with RA, in 20-25% of patients with systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
and in 35-40% of patients with mixed connective tissue disease
Mixed connective tissue disease
In medicine, mixed connective tissue disease , commonly abbreviated as MCTD, is an autoimmune disease, in which the body's defense system attacks itself. It was characterized in 1972....
, being rare or absent in other arthritic conditions with a non-autoimmune etiology. Anti-RA33 can be easily detected by immunoblotting employing crude nuclear extracts or the recombinant antigen. Fo routine diagnostics also ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
can be employed which is somewhat less sensitive than immunoblotting. The use of indirect immunofluorescence is of limited usefulness for detecting anti-RA33.
The pathogenic role of anti-RA33 is not fully understood. Anti-RA33 and T cells directed against RA33, that can be found in about 60% of RA patients might contribute to autoimmune inflammation by immune complex
Immune complex
An immune complex is formed from the integral binding of an antibody to a soluble antigen. The bound antigen acting as a specific epitope, bound to an antibody is referred to as a singular immune complex....
formation or by virtue of secretion of cytokines that may initiate and drive the pathogenic process. Of note, anti-RA33 are detectable already in the earliest disease stage of RA or even years before the onset of actual clinical disease. The positive predictive value
Positive predictive value
In statistics and diagnostic testing, the positive predictive value, or precision rate is the proportion of subjects with positive test results who are correctly diagnosed. It is a critical measure of the performance of a diagnostic method, as it reflects the probability that a positive test...
of anti-RA33 is 74%. However, anti-RA33 are not associated with bone erosions or disease activity. In the absence of rheumatoid factor
Rheumatoid factor
Rheumatoid factor is an autoantibody most relevant in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG. RF and IgG join to form immune complexes that contribute to the disease process...
and anti-citrullinated protein antibody
Anti-citrullinated protein antibody
Anti-citrullinated protein antibodies or anti-cyclic citrullinated protein antibodies are autoantibodies that are frequently detected in the blood of rheumatoid arthritis patients...
they are associated with a milder disease course of RA rather.