American College of Rheumatology (ACR) response criteria
ACR response criteria include changes in number of swollen joints, tender joints, physician global assessment of disease, patient global assessment of disease, patient assessment of pain, C-reactive protein, erythrocyte sedimentation rate, and health assessment questionnaire score.
ACR20 response
An ACR20 response requires a patient to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five indices: physician global assessment of disease, patient global assessment of disease, pain, C-reactive protein, erythrocyte sedimentation rate and health assessment questionnaire score.
ACR50 response
An ACR50 response requires a patient to have a 50% reduction in the number of swollen and tender joints, and a reduction of 50% in three of the following five indices: physician global assessment of disease, patient global assessment of disease, pain, C-reactive protein, erythrocyte sedimentation rate and health assessment questionnaire score.
ACR70 response
An ACR70 response requires a patient to have a 70% reduction in the number of swollen and tender joints, and a reduction of 70% in three of the following five indices: physician global assessment of disease, patient global assessment of disease, pain, C-reactive protein, erythrocyte sedimentation rate and health assessment questionnaire score.
Anakinra
The generic name for interleukin-1 receptor antagonist (IL-1ra), the recombinant nonglycosylated form of the naturally occurring IL-1Ra. Anakinra is produced and purified from E. coli (see interleukin-1 receptor antagonist).
Anticytokine-based therapy
A disease treatment that exerts its effect through neutralising, blocking, or down-regulating a cytokine implicated in a disease process.
Anti-inflammatory cytokines
Promoting a reduction in inflammation. An anti-inflammatory cytokine possesses biological properties that reduce inflammation either by suppressing proinflammatory genes or inducing genes coding for anti-inflammatory products.
Biologicals
Agents produced by gene technology that mimic the action of native molecules in the human body and specifically target molecules involved in disease.
Chondrocyte
A mature cartilage cell embedded within the cartilage matrix. Chondrocytes synthesise matrix proteins such as collagen.
Corticosteroids
See glucocorticoids.
C-reactive protein
A β-globlin found in the serum of various persons with certain inflammatory, degenerative, and neoplastic diseases including rheumatoid arthritis. High levels of the protein are indicative of acute inflammation.
Cytokines
Any of more than 150 proteins or glycoproteins that function as messengers between cells, regulating the activities of cells through interactions with specific cell-surface receptors.
Disease-modifying antirheumatic drugs (DMARDs)
Agents that relieve the symptoms of rheumatoid arthritis and help to control the disease by modifying the actual disease process.
Erythrocyte sedimentation rate (ESR)
The distance that red blood cells (erythrocytes) settle in unclotted blood in one hour. Commonly used in rheumatoid arthritis to assess degree of inflammation.
Etanercept
The generic name for a dimeric fusion protein consisting of the extracellular ligand-binding domains of the human tumour necrosis factor receptor type II linked to the Fc portion of human immunoglobulin G1. Etanercept is also known as sTNF-RII:Fc.
Glucocorticoids
Glucocorticoids, also called corticosteroids, are a group of anti-inflammatory drugs that are related to cortisol, a natural steroid hormone produced by the body.
Health Assessment Questionnaire (HAQ)
The HAQ is a validated, self-administered questionnaire composed of twenty items relating to function and four items relating to aids and devices. These comprise eight subscales: dressing and grooming, arising, hygiene, reach, eating, walking, grip, and activities. Items are scored from 0 (able to function without difficulty) to 3 (unable to function). The HAQ disease index is a weighted sum of the scale scores, with a higher score indicating poorer function. Decreases in the HAQ disease index exceeding -0.19 to -0.22 are considered to be clinically important.
Infliximab
The generic name for a neutralising chimeric (mouse-human) human TNF-α-specific monoclonal antibody.
Interferon-γ (IFN-γ)
A cytokine produced primarily by activated T helper cell type I cells that has a variety of immunomodulatory effects. IFN-γ activates monocytes and macrophages to release inflammatory cytokines, stimulates CD4+ T cells as part of the T helper cell type I response, and (together with IL-2) activates CD8+ T cells to participate in cell-mediated immunity.
Interleukin
A term used to describe a cytokine, originally used to refer to protein messengers among leukocytes, or between leukocytes and nonimmune cells. See cytokine.
Interleukin-1 (IL-1)
A cytokine noted for its broad range of proinflammatory properties on a wide variety of cells. IL-1 exists in two forms, IL-1α and IL-1β, which are transcribed from closely related but distinct genes.
Interleukin-1α (IL-1α)
One of two forms of IL-1, IL-1α is synthesised as a 31 kilo Dalton biologically active precursor and is found diffusely in the cytosol and on the cell membrane. Mature IL-1α is rarely found in the extracellular space.
Interleukin-1β (IL-1β)
One of two forms of IL-1. Like IL-1α, IL-1β is synthesised as a 31 kilo Dalton precursor (pro-IL-1β). However, pro-IL-1β is not fully active. After cleavage by IL-1β-converting enzyme, mature IL-1β is secreted into the extracellular space.
Interleukin-1 receptor antagonist (IL-1Ra)
An endogenous molecule that binds to the IL-1 type I receptor and blocks the binding and biological activity of IL-1. IL-1ra is a recombinant nonglycosylated form of the naturally occurring IL-1Ra (see anakinra).
Interleukin-1 receptor type I (IL-1RI)
The ligand-binding chain of the IL-1 receptor. Both membrane-associated and soluble forms exist. Upon binding IL-1, membrane-bound IL-1RI undergoes a conformational change and forms a complex with IL-1 receptor accessory protein. This complex then initiates signal transduction.
Macrophage
A mononuclear phagocytic cell involved in the production of antibodies and cell-mediated immune responses, particularly in presenting antigens to lymphocytes. Macrophages secrete a variety of immunoregulatory molecules, including proinflammatory cytokines.
Matrix metalloproteases (MMPs)
Metalloproteases are a group of proteolytic enzymes the incorporate a metal atom as part of their catalytic activity. Matrix metalloproteases are enzymes (including collagenases, stromelysins, and gelatinases) that hydrolyse proteins in the extracellular matrix. The synthesis and secretion of MMPs are induced by a number of cytokines, including IL-1 and TNF-α.
Monocyte
A mononuclear phagocytic cell that circulates in the blood before becoming a macrophage.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Agents that are administered to relieve the pain and suppress inflammation associated with rheumatoid arthritis by blocking the action of prostaglandins.
Osteoblast
A cell derived from bone marrow stromal cells that forms bone.
Osteoclast
A large, multinucleated cell, possibly derived from monocytes or macrophages, that resorbs bone.
Osteoprotegerin (OPG)
A soluble member of the TNF receptor superfamily that binds receptor activator of NF-κB (RANK), thereby inhibiting osteoclast maturation and activation and ultimately decreasing osteoclastic bone resorption. Also known as osteoclastogenesis inhibitory factor.
Osteoprotegerin ligand (OPGL)
A member of the TNF cytokine superfamily that stimulates the maturation and activation of osteoclasts, thereby increasing bone resorption. The production of OPGL by marrow stromal cells and osteoblasts is increased by TNF-α and particularly by IL-1β, as well as by hormones and prosteoglandins. Also known as receptor activator of NF-κB ligand (RANKL) or osteoclast differentiation factor (ODF).
Prostaglandin-E2 (PGE2)
A member of the prostaglandin class of soluble physiological mediators, which are derived from arachidonic acid via the cyclooxygenase pathway. The effects of prostaglandins include fever, pain, vasodilation, smooth muscle relaxation, and various effects on nerve transduction and renal function. In addition, prostaglandins affect cytokine gene expression.
Prostanoids
Derivatives of prostanoic acid, including prostaglandins and thromboxanes.
Proinflammatory cytokines
Cytokines that possess several biological properties that result in inflammation, usually by increasing expression of genes coding for other inflammatory molecules.
Pannus
A membrane of synovial granulation tissue that covers the articular cartilage and progressively destroys the underlying articular cartilage.
Receptor activator of NF-κB ligand (RANKL)
See osteoprotegerin ligand.
Rheumatoid arthritis
Common systemic disease occurring more often in women, which affects connective tissue. Arthritis is the dominant clinical manifestation, involving many joints, especially those of the hands and feet. The course is variable, but often chronic and progressive, leading to deformity and disability.
Soluble cytokine receptor
A cytokine receptor that lacks transmembrane and intracellular domains and is found in the extracellular compartment. Soluble cytokine receptors retain ligand binding activity and can reduce ligand binding to membrane-associated cytokine receptors, serving as inhibitors or ligand passers.
Synovial membrane (synovium)
The connective tissue that lines the cavity of a synovial joint and produces the synovial fluid.
Synovitis
Inflammation of the synovial membrane, especially that of a joint.
Tumour necrosis factor-α (TNF-α)
A proinflammatory cytokine with multiple effects, including activation of vascular endothelium, induction of apoptosis, stimulation of the innate immune response, and induction of cachexia through alterations in metabolism. TNF-α is a central proinflammatory mediator in rheumatoid arthritis and other diseases. Mature, soluble TNF-α is a homotrimer formed from three 17 kilo Dalton peptide chains.
Tumour necrosis factor receptor type I (TNF-RI)
One of two types of TNF receptor. TNF-RI exists as both a membrane-associated form and as a soluble form (sTNF-RI), in which the shed extracellular domain may serve as a natural inhibitor of TNF-α activity. In contrast to TNF-RII, TNF-RI binds nearly irreversibly to soluble TNF-α. Binding of TNF-α to TNF-RI can cause either activation of proinflammatory properties or the induction of apoptosis, depending upon which intracellular signalling pathway is activated.
Tumour necrosis factor receptor type II (TNF-RII)
One of two types of TNF receptor. Like TNF-RI, TNF-RII exists as both a membrane-associated form and as a soluble form (sTNF-RII), which may serve as a natural inhibitor of TNF-α activity. Unlike TNF-RI, TNF-RII may rapidly dissociate from soluble TNF-α and may therefore serve to pass soluble ligand to TNF-RI for signal transduction.
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