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Anti-Citrullinated Protein Antibodies. Abbreviation for autoantibodies specific for citrullinated proteins. Determination of ACPA is included in the 2010 ACR/EULAR diagnostic criteria for rheumatoid arthritis.


The American College of Rheumatology, The American College of Rheumatology's mission is advancing rheumatology. The organization is for physicians, health professionals, and scientists that meets the mission through programs of education, research, advocacy and practice support.

Adaptive immunity

The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth. The adaptive immune response provides the immune system with the ability to recognize and remember specific pathogens to generate immunity against pathogens. It is adaptive because the body's immune system prepares itself for future encounters.


Anti-Neutrophil Cytoplasmic Antibodies. Group of autoantibodies, mainly of the IgG type, against antigens in the cytoplasm of neutrophil granulocytes. Are often related to systemic autoimmune vasculitis – ANCA-associated vasculitides.


Anti-Phospholipid Syndrome, an autoimmune disease characterized by abnormal formation of blood clots both in arteries and veins.

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Cytoplasmic antineutrophil cytoplasmic antibodies. ANCA that are specific for antigens distributed in the neutrophil cytoplasm. When detected by Indirect Immunofluorescence technique (IIF), it is referred to as C-ANCA pattern. Often the specific antigen consists of PR3. C-ANCA specific for PR3 is associated with Granulomatosis with polyangitis (GPA), previously named Wegener’s granulomatosis)


Tumor originating from neuroendocine cells. The name was coined in 1907 by Siegfried Oberndorfer.


Cardiolipin (CL) is a form of diphosphatidylglycerol lipid found primarily in the inner membrane of mitochondria. Patients with antibodies specific for cardiolipin may suffer from Antiphospholipid syndrome (APS) clinically demonstrated by recurrent thrombotic events and/or recurrent spontaneous abortions. Anti-cardiolipin antibodies may also be found and increased in numerous other conditions such as syphilis (Wassermann test), systemic lupus erythematosus, malaria and tuberculosis.


Cyclic Citrullinated Peptide

CCP High sensitive, anti-

The antigen used in the test is MCV. In the literature, the anti-MCV test has been shown to have both lower specificity as well as sensitivity for rheumatoid arthritis compared with anti-CCP2. However, the anti-MCV test may have its use as a complement to the anti-CCP2 test. (Ref: Pruijn GJ, Wiik A, van Venrooij WJ. Arthritis Res Ther. 2010;12(1):203. Epub 2010)

CCP, anti-

Assay for the determination of autoantibodies specific for a synthetically designed and optimized antigen consisting of a cyclic polypeptide containing citrulline. The structure and design of the CCP is patent protected. The assay was developed by the group of Professor van Venrooij in Nijmegen, the Netherlands in collaboration with Euro Diagnostica. The assay has been on the market for more than a decade and nowadays stands for an assay concept based on a small synthetic citrullinated cyclic peptide as antigen (see also anti-CCP2). Regarded as a cardinal test for rheumatoid arthritis.

CCP1, anti-

The first version of the cyclic citrullinated peptide antigen launched in 2000. Often referred to as the first generation assay. The structure of the CCP1 is derived from the synovial protein fillaggrin.

CCP2, anti-

(Immunoscan CCPlus) A further development of the first generation anti-CCP test. The antigen consists of cyclic citrullinated polypeptides with a unique peptide sequence, optimized for sensitivity and specificity in diagnosing rheumatoid arthritis. More than 12 million peptides were screened to identify the optimal peptide structures. Most of the anti-CCP tests on the market are of the anti-CCP2 version. Likewise, a vast majority of all the literature on the clinical evaluation of tests for autoantibodies against citrullinated epitopes are about the anti-CCP2.

CCP3/CCP3.1, anti-

A form of anti-CCP test marketed as an improved third generation test although the anti-CCP3 tests have been shown in the literature to have both lower sensitivity, but in particular, inferior specificity in comparison with the anti-CCP2 assay. The anti-CCP3.1 detects IgA in addition to IgG. The rationale behind testing IgA has been questioned by the scientific community. (Ref: Pruijn GJ, Wiik A, van Venrooij WJ. Arthritis Res Ther. 2010;12(1):203. Epub 2010)

Chromogranin A

Chromogranin A (CgA) is a member of the granin family of neuroendocrine secretory proteins, i.e. it is located in secretory vesicles of neurons and endocrine cells. CgA is produced by neuroendocrine cells such as enterochromaffin cells of the gastrointestinal tract. Serum level of CgA has been shown to be a good diagnostic marker for neuroendocrine tumors (NET).


Citrulline is an α-amino acid produced from arginine by a reaction catalyzed by a family of enzymes called peptidylarginine deiminases (PADs). The conversion from arginine to citrulline is called citrullination or deimination. The process transforms the positively charged arginine to a neutral citrulline, which has significant effect on the structure of the citrullinated protein.


Cartilage oligomeric matrix protein (COMP) is a noncollagenous extracellular matrix (ECM) protein. It consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. Oligomerization results from formation of a five-stranded coiled coil and disulfide bonds. The serum levels of COMP reflects the bioactivity of cartilage and is therefore a valuable marker for cartilage breakdown.

Complement system

The complement system is an important part of the innate immunity. It consists of more than 25 small proteins found in the blood circulating as inactive precursors When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages which leads to massive amplification of the response. Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway.

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DMARD (Disease-modifying antirheumatic drugs)

A group of unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression. Their uses have now been expanded to other autoimmune diseases such as Crohn’s disease and Systemic Lupus Erythematosus. A well-known example is TNF-α inhibitor.

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The European League Against Rheumatism (EULAR) is the organization which represents the patient, health professional and scientific societies of rheumatology of all the European nations. EULAR endeavors to stimulate, promote, and support the research, prevention, treatment and rehabilitation of rheumatic diseases. In line with UEMS, EULAR defines rheumatology as including rheumatic diseases of the connective tissue, locomotor and musculoskeletal systems.

Extra articular manifestations (EAM)

Systemic or extra-articular manifestations are common in patients with rheumatoid arthritis (RA). Extra-articular ("outside the joints") manifestations other than anemia (which is very common) are clinically evident in about 15–25% of individuals with rheumatoid arthritis. There are a number of different EAM such as rheumatoid nodule, vasculitis, inflammation of the lungs, amyloidosis of the kidneys, atherosclerosis, pericarditis/endocarditis and anemia.

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Ficolins are humoral molecules of the innate immune systems which recognize carbohydrate molecules on pathogens, apoptotic and necrotic cells. Three different ficolins have been identified in humans: L-ficolin, H-ficolin and M-ficolin (also referred to as ficolin-2, -3 and -1, respectively). They are all soluble oligomeric defense proteins with lectin-like activity and structurally similar to the mannan-binding lectin (MBL). Upon recognition of an infectious agent, ficolins initiate the lectin pathway of complement activation through attached serine proteases (MASPs).

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Innate immunity

The innate immune system is also known as the non-specific immune system and first line of defense. It involves cells and mechanisms that defend the host from infection by other organisms in a non-specific manner. The innate immune system basically includes three major components, i.e. barriers, inflammation and complement activation.

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Jo-1 antigen

Histidyl tRNA synthetase is an amino acyl-tRNA synthetase which is an autoantigen in some patients with polymyositis.

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The membrane attack complex (MAC) is typically formed on the surface of pathogenic bacterial cells as a result of the activation of the complement system. The membrane-attack complex (MAC) forms transmembrane channels. These channels disrupt the phospholipid bilayer of target cells, leading to cell lysis and death. MAC is assembled by the combination of complement factors C5b-C6-C7-C8-C9.


Mannan-binding lectin has an oligomeric structure (400-700 kDa), built of subunits that contain three presumably identical peptide chains. MBL is encoded by the MBL2 gene located on chromosome 10. In addition there is a pseudogene, MBL1, encoding a truncated nonfunctional protein. A number of structural mutations in exon 1 of the human MBL2 gene have been demonstrated, which independently reduce the level of functional serum MBL by disrupting the collagenous structure of the protein. Moreover, several nucleotide substitutions in the promoter region of the MBL2 gene affect the MBL serum concentration. MBL binds to carbohydrates (i.e. mannose and fucose residues) found on the surface of many pathogens Binding of MBL results in activation of the lectin pathway of the complement system.


Myeloperoxidase. A peroxidase most abundantly expressed in neutrophil granulocytes. MPO has a heme pigment giving it a greenish color. The molecular weight is about 150 kDa and the enzyme consists of four chains.


Anti-Neutrophil Cytoplasmic Antibodies (ANCA) specific for MPO

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Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. Some are benign, while some are cancers. They most commonly occur in the intestine, but are also found in the lung and the rest of the body. They are often slow-growing tumors. Although there are many kinds of NETs, they are treated as a group because these neoplasms share common features, such as looking similar, having special secretory granules, and often producing biogenic amines and polypeptide hormones.

Neutrophil granulocyte

The most abundant white blood cell. Neutrophils are recruited to the site of injury within minutes following trauma and are the hallmark of acute inflammation. It is a member of the class of polymorphonuclear cells, so called because of the lobed appearance of the nucleus. Neutrophils express and release cytokines and play a key role in the front-line defense against invading pathogens. Basically they have three strategies for directly attacking micro-organisms: phagocytosis (ingestion), release of soluble anti-microbials (including enzymes such as PR3 and MPO), and generation of neutrophil extracellular traps (NETs).

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Osteoarthritis (OA) also known as degenerative arthritis or, is a group of abnormalities involving degradation of joints, including articular cartilage and subchondral bone. Symptoms may include joint pain, tenderness, stiffness, locking, and sometimes an effusion. A variety of causes have been suggested that may initiate processes leading to loss of cartilage, such as hereditary, developmental, metabolic, and mechanical. OA is the most common form of arthritis, and the leading cause of chronic disability.

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Perinuclear antineutrophil cytoplasmic antibodies. ANCA specific for antigens distributed close to the nucleus of the neutrophil. This pattern occurs because the vast majority of the antigens targeted by ANCAs are positively charged at neutral pH. During ethanol fixation, antigens which are more cationic migrate and localize around the nucleus, chemically attracted by the negatively charged DNA. Antibody staining therefore results in fluorescence of the region around the nucleus. The staining is in a sense an artifact caused by the ethanol treatment of the cells. Often the specific ANCA antigen consists of MPO but can be a number of other specificities as well.


Maternal antibodies to the amino acid (aa) 200–239 (p200) of the Ro52 protein have been suggested as a serological marker for an increased risk of having a child with congenital heart block (CHB)


Polyarthritis is any type of arthritis which involves several joints simultaneously. It is often associated with autoimmune conditions such as rheumatoid arthritis.


Proteinase 3 is a serine protease with trypsin-like specificity expressed mainly in neutrophil granulocytes.


Anti-Neutrophil Cytoplasmic Antibodies (ANCA) specific for PR3

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Rheumatoid arthritis (RA)

Chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks flexible (synovial) joints.


The Ro/La system is considered as an heterogeneous antigenic complex, constituted by three different proteins (52 kDa Ro, 60 kDa Ro and La) and four small RNAs particles. Anti-Ro/SSA are the most prevalent specificity among many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, sub-acute cutaneous LE (SCLE), neonatal lupus and primary biliary cirrhosis. In contrast, anti-La/SSB is more associated with Sjögren's syndrome (SS)

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Scl-70 antigen

Scl-70 is a fragment of topoisomerase 1. Autoantibodies against Scl-70 are specific for scleroderma. Scl is an abbreviation of scleroderma and 70 refers to the 70 kDa extractable immunoreactive fragment that can be obtained from the larger (100–105 kD) topoisomerase


Systemic Lupus erythematosus is a systemic autoimmune disease that can affect any tissue/organ in the form of inflammation and tissue damage. The course of the disease is characterized by periods of active disease (flares) separated by periods of remission.

Sm antigen

Smith antigen. Named after Stephanie Smith, the patient in whom anti-Sm antibodies was first discovered. The Smith antigen is a complex of ribonucleic acid (RNA) molecules and multiple proteins, including uridine-rich small nuclear RNAs (snRNA)


Inflammation of the synovial membrane, which is the membrane lining the joints which possess cavities, known as synovial joints. Synovitis occurs in association with rheumatoid arthritis as well as other conditions.

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