Detection of

autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...

against mutated citrullinated vimentin is part of

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

(RA) diagnostics, especially in sera negative for

rheumatoid factor 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 co ...

(RF negative sera). Anti-MCV antibodies are a member of the ACPA family, a group of the so-called antibodies to citrullinated protein/peptide antigens. Rheumatoid arthritis is an

autoimmune disorder An autoimmune disease is a condition that results from an anomalous response of the adaptive immune system, wherein it mistakenly targets and attacks healthy, functioning parts of the body as if they were foreign organisms. It is estimated tha ...

. Detection of specific autoantibodies (antibodies directed against the body’s own tissue) such as rheumatoid factors and ACPAs may provide indication of the disease. In many cases, autoimmune diagnostics are crucial for diagnosing RA correctly and already in the disease’s early stages, when typical symptoms often are lacking but when medical therapy is most effective.

Basics

Citrullination Citrullination or deimination is the conversion of the amino acid arginine in a protein into the amino acid citrulline. Citrulline is not one of the 20 standard amino acids encoded by DNA in the genetic code. Instead, it is the result of a post-tr ...

is a modification of proteins where a

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

in the

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

is replaced with an

oxygen Oxygen is a chemical element; it has chemical symbol, symbol O and atomic number 8. It is a member of the chalcogen group (periodic table), group in the periodic table, a highly reactivity (chemistry), reactive nonmetal (chemistry), non ...

, converting it into

citrulline The organic compound citrulline is an α-amino acid. Its name is derived from '' citrullus'', the Latin word for watermelon. Although named and described by gastroenterologists since the late 19th century, it was first isolated from watermelon in ...

. The modified (citrullinated) protein may be identified by as foreign, provoking an autoimmune inflammation response. Various kinds of citrullinated proteins have been detected in the joints of RA patients. One of these is Sa antigen, now known as mutated citrullinated vimentin (MCV). Citrullination of

vimentin Vimentin is a structural protein that in humans is encoded by the ''VIM'' gene. Its name comes from the Latin ''vimentum'' which refers to an array of flexible rods. Vimentin is a Intermediate filament#Type III, type III intermediate filamen ...

plays a decisive role in RA pathogenesis.

Significance

In rheumatology diagnostics, autoantibodies against mutated citrullinated vimentin (anti-MCV) are of prominent diagnostic and prognostic value. Their significance is greater than that of rheumatoid factor. Recently a serological point-of-care test (POCT) for the early detection of RA has been developed. This assay combines the detection of rheumatoid factor and anti-MCV for diagnosis of rheumatoid arthritis and shows a sensitivity of 72% and specificity of 99.7%. Anti-MCV are used as efficient

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

s for estimating progress of rheumatoid arthritis. Main advantage of testing for anti-MCV is the early appearance of the anti-MCV antibodies, what allows for detection of early RA and submits adequate therapy just after the disease’s onset. Moreover, anti-MCV titres show strong correlation to disease activity, disease severity and the success of therapy.

References

{{reflist Arthritis