Anti-nRNP

Anti-nRNP is a type of antibody.^[1][2]

They are autoantibodies against some ribonucleoproteins.^[3]

Anti-nRNP antibodies can be elevated in mixed connective tissue disease.^[4]

Anti-nRNP antibody

Anti-nuclear Ribonucleoprotein (Anti-nRNP) antibodies are a type of autoantibody, which are antibodies that wrongly target and attack a person's own cells, proteins or tissues. In particular, anti-nRNPs are directed against nuclear ribonucleoproteins (nRNPs), which are complexes composed of proteins and nucleic acids^[5]. These ribonucleoproteins play a critical role in various cellular processes, including RNA processing and gene expression^[6].

Background

The human immune system relies on antibodies, these are specialized proteins produced by B cells in response to the presence of antigens. Antigens are typically foreign molecules that are parts of bacteria, viruses or other pathogens that trigger an immune response. Antibodies bind to these antigens to neutralize them, block their activity, or mark them for destruction by other immune system cells.

In autoimmune diseases, the immune system fails to distinguish between self and non-self. This causes it to produce autoantibodies that target the body's own healthy tissues. Autoantibodies can cause inflammations, tissue damage and contribute to the progression of various chronic diseases^[7].  

Target

Anti-nRNP antibodies target small nuclear ribonucleoproteins (snRNPs)^[8]. It specifically the U1-snRNP complex which is a part of the spliceosome. The spliceosome is an essential cellular component responsible for the removal of introns from pre-messenger RNA, an important step in processing genetic information before it is translated into proteins. The spliceosome is made up of 5 different complexes, U1, U2, U4, U5 and U6. All of these complexes contain the same 7 Smith (Sm) proteins. U1-snRNP is made up of the 7 core Sm proteins, U1-RNA and 3 unique proteins^[9]. The proteins most commonly targeted within the complex are the RNP68/70, RNPA and RNPC^[10].

Testing

An enzyme-linked immunosorbent assay (ELISA) is one of the most common ways for detecting anti-U1 RNP antibodies in patient sera. In this procedure, purified or recombinant U1-RNP antigens are placed into microplate wells. After they block nonspecific binding sites, diluted patient serum is added to the wells and incubated. If specific autoantibodies are present, they can bind to the immobilized antigen. A secondary enzyme-conjugated anti-human IgG antibody is added, that it is followed by a substrate that produces a color change. This is read by spectrophotometry and compared to a standard curve to measure the levels of antibodies ^[11]. Reference ranges are specific to each laboratory, and results must be interpreted in the context of clinical findings^[12]. This method is highly sensitive and frequently used to support diagnosis in patients with suspected MCTD or other connective tissue diseases^[13].

Clinical significance

Anti-nRNP antibodies are most strongly associated with Mixed Connective Tissue Disease (MCTD), a condition that exhibits overlapping symptoms with systemic lupus erythematosus (SLE), scleroderma, and rheumatoid arthritis^[14][15]. The detection of high titers of anti-U1 snRNP antibodies in the sera of patients is considered a hallmark of MCTD and is commonly used in its diagnosis^[15][16].

In addition to MCTD, anti-nRNP antibodies have been observed in a variety of other autoimmune disorders including^[17][18][19]:

• Systemic Lupus Erythematosus (SLE)
• Systemic Sclerosis (SS)
• Primary Sjorgen's Syndrome (pSS)
• Raynaud's phenomenon
• Scleroderma
• Rheumatoid Arthritis

The pathogenic role of anti-nRNP antibodies in these diseases varies, and their presence may only reflect immune system deregulation rather than being the direct cause of disease symptoms. Yet, they have served as valuable biomarkers for both diagnosis and monitoring of diseases.

See also

• snRNP70