RA33, also known as heterogeneous nuclear ribonucleoprotein A2/B1, is an autoantigen in human systemic autoimmune diseases.
In 1989, a novel class of autoantibodies was detected in sera of patients with rheumatoid arthritis (RA), which were directed against a protein with an estimated molecular mass of 33 kDa in nuclear extracts from HeLa cells. [1] The antigen was therefore named RA33. Protein sequencing of highly purified RA33 revealed that it was identical to hetergoneous nuclear ribonucleoprotein A2/B1 (hnRPA2B1). [2] Nowadays, the name anti-RA33 defines autoantibodies that are directed against hnRNP A2 and its splice variant hnRNP B1. Anti-RA33 occur in approximately 15-35% 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 forms of arthritis. [3] Anti-RA33 antibodies can be easily detected by immunoblotting employing crude nuclear extracts or the recombinant antigen. ELISA can also be employed which has been found to be less sensitive than immunoblotting.
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.
HeLa is 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 died of cancer on October 4, 1951. The cell line was found to be remarkably durable and prolific which warrants its extensive use in scientific research.
Systemic lupus erythematosus (SLE), also known simply as lupus, is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary between people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission during which there are few symptoms.
The pathogenic role of anti-RA33 antibodies is not fully understood. Anti-RA33 antibodies and T cells directed against RA33 might contribute to autoimmunity and inflammation by immune complex formation or by virtue of secretion of cytokines that may initiate and drive the pathogenic process. [4] Of note, anti-RA33 are detectable already in the earliest disease stage of RA or even years before the onset of actual clinical disease. However, anti-RA33 antibodies are not associated with significant bone erosions or disease activity. In the absence of rheumatoid factor and anti-citrullinated protein antibody they are associated with a milder disease in RA.
An immune complex, sometimes called an antigen-antibody complex, is a molecule formed from the integral binding of an antibody to a soluble antigen. The bound antigen and antibody act as a unitary object, effectively an antigen of its own with a specific epitope. After an antigen-antibody reaction, the immune complexes can be subject to any of a number of responses, including complement deposition, opsonization, phagocytosis, or processing by proteases. Red blood cells carrying CR1-receptors on their surface may bind C3b-coated immune complexes and transport them to phagocytes, mostly in liver and spleen, and return to the general circulation.
Rheumatoid factor (RF) is the autoantibody that was first found in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG and different RFs can recognize different parts of the IgG-Fc. RF and IgG join to form immune complexes that contribute to the disease process.
