Cell-bound complement activation products

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Cell-Bound Complement Activation Products (CB-CAPs) or complement split products, refers to complement activation fragments, C4d, that are bound covalently to somatic cells, as a result of activation of the classical complement pathway. [1] They appear potentially useful for the diagnosis of systemic lupus erythematosus as of 2015. [2]

A somatic cell or vegetal cell is any biological cell forming the body of an organism; that is, in a multicellular organism, any cell other than a gamete, germ cell, gametocyte or undifferentiated stem cell.

Systemic lupus erythematosus inflammation of connective tissue marked by skin rashes, joint pain and swelling, inflammation of the kidneys and inflammation of the tissue surrounding the heart.

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.

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Medical use

CB-CAPs can be used in the diagnosis and monitoring of SLE. [3] Their efficacy is aided by the ability to be measured throughout the lifespans of erythrocytes, b-lymphocytes. [4]

Research

Research into the development of CB-CAPs has been advocated by the Lupus Foundation of America. [5]

Related Research Articles

Autoimmunity is the system of immune responses of an organism against its own healthy cells and tissues. Any disease that results from such an aberrant immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, sarcoidosis, systemic lupus erythematosus (SLE), Sjögren's syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM) and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.

Anti-nuclear antibody autoantibody that binds to contents of the cell nucleus

Antinuclear antibodies are autoantibodies that bind to contents of the cell nucleus. In normal individuals, the immune system produces antibodies to foreign proteins (antigens) but not to human proteins (autoantigens). In some individuals, antibodies to human antigens are produced.

Classical complement pathway Any process involved in the activation of any of the steps of the classical pathway of the complement cascade which allows for the direct killing of microbes, the disposal of immune complexes, and the regulation of other immune processes.

The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and IgM.

Complement receptor 1 protein-coding gene in the species Homo sapiens

Complement receptor type 1 (CR1) also known as C3b/C4b receptor or CD35 is a protein that in humans is encoded by the CR1 gene.

Lupus nephritis glomerulonephritis that is characterized by inflammation of the kidneys resulting from systemic lupus erythematosus

Lupus nephritis is an inflammation of the kidneys caused by systemic lupus erythematosus (SLE), an autoimmune disease. It is a type of glomerulonephritis in which the glomeruli become inflamed. As the result of SLE, the cause of glomerulonephritis is said to be secondary and has a different pattern and outcome from conditions with a primary cause originating in the kidney.

Extractable Nuclear Antigens (ENAs) are over 100 different soluble cytoplasmic and nuclear antigens. The are known as “extractable” because they can be removed from cell nuclei using saline and represent six main proteins: Ro, La, Sm, RNP, Scl-70, Jo1. Most ENAs are part of spliceosomes or nucleosomes complexes and are a type of small nuclear ribonucleoprotein (snRNPS). The location in the nucleus and association with spliceosomes or nucleosomes results in these ENAs being associated with additional RNA and proteins such as polymerases. This quality of ENAs often makes it difficult to purify and quantify their presence for clinical use.

Integrin alpha M protein-coding gene in the species Homo sapiens

Integrin alpha M (ITGAM) is one protein subunit that forms heterodimeric integrin alpha-M beta-2 (αMβ2) molecule, also known as macrophage-1 antigen (Mac-1) or complement receptor 3 (CR3). ITGAM is also known as CR3A, and cluster of differentiation molecule 11B (CD11B). The second chain of αMβ2 is the common integrin β2 subunit known as CD18, and integrin αMβ2 thus belongs to the β2 subfamily integrins.

Belimumab is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator (BLyS). It is approved in the United States, Canada, and Europe to treat systemic lupus erythematosus (SLE).

B-cell activating factor protein-coding gene in the species Homo sapiens

B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans is encoded by the TNFSF13B gene. BAFF is also known as B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) and the Dendritic cell-derived TNF-like molecule.

Discoid lupus erythematosus

Discoid lupus erythematosus is the most common type of chronic cutaneous lupus (CCLE), an autoimmune skin condition on the lupus erythematosus spectrum of illnesses. It presents with red, inflamed, coin-shaped patches of skin with a scaling and crusty appearance, most often on the scalp, cheeks, and ears. Hair loss may occur if the lesions are on the scalp. The lesions can then develop severe scarring, and the centre areas may appear lighter in color with a rim darker than the normal skin. These lesions can last for years without treatment.

Interferon alpha-1 protein-coding gene in the species Homo sapiens

Interferon alpha-1/13 is a protein that in humans is encoded by the IFNA1 gene.

Lupus erythematosus

Lupus erythematosus is a collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks healthy tissues. Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs. The most common and severe form is systemic lupus erythematosus.

Anti-dsDNA antibodies

Anti-double stranded DNA (Anti-dsDNA) antibodies are a group of anti-nuclear antibodies (ANA) the target antigen of which is double stranded DNA. Blood tests such as enzyme-linked immunosorbent assay (ELISA) and immunofluorescence are routinely performed to detect anti-dsDNA antibodies in diagnostic laboratories. They are highly diagnostic of systemic lupus erythematosus (SLE) and are implicated in the pathogenesis of lupus nephritis.

Atacicept is a recombinant fusion protein designed to inhibit B cells, thereby suppressing autoimmune disease. The designer protein combines the binding site for two cytokines that regulate maturation, function, and survival of B cells - B-lymphocyte stimulator (BLyS) and A proliferation-inducing ligand (APRIL), with the constant region of immunoglobin. Atacicept blocks activation of B cells by the tumor necrosis factor receptor superfamily member 13B, a transmembrane receptor protein found predominantly on the surface of B cells. Like the monoclonal antibody belimumab, atacicept blocks the binding of BLyS, but it also blocks APRIL. Binding of these TACI ligands induces proliferation, activation, and longevity of B cells and thus their production of autoantibodies. Atacicept is thought to selectively impair mature B cells and plasma cells with less impact on progenitor cells and memory B cells.

suPAR, soluble urokinase-type plasminogen activator receptor is the soluble form of uPAR. uPAR is a membrane bound receptor for uPA, otherwise known as urokinase as well as Vitronectin. suPAR results from the cleavage and release of membrane-bound uPAR. suPAR concentration positively correlates to the activation level of the immune system and is present in plasma, urine, blood, serum, and cerebrospinal fluid. suPAR is a marker of disease severity and aggressiveness.

For women with systemic lupus erythematosus (SLE), pregnancy can present some particular challenges for both mother and child.

Autoimmune optic neuropathy (AON), sometimes called autoimmune optic neuritis, may be a forme fruste of systemic lupus erythematosus (SLE) associated optic neuropathy. AON is more than the presence of any optic neuritis in a patient with an autoimmune process, as it describes a relatively specific clinical syndrome. AON is characterized by chronically progressive or recurrent vision loss associated with serological evidence of autoimmunity. Specifically, this term has been suggested for cases of optic neuritis with serological evidence of vasculitis by positive ANA, despite the lack of meeting criteria for SLE. The clinical manifestations include progressive vision loss that tends to be steroid-responsive and steroid dependent.

Neuropsychiatric systemic lupus erythematosus or NPSLE refers to the neurological and psychiatric manifestations of systemic lupus erythematosus. SLE is a disease in which the immune system attacks the body's own cells and tissues. It can affect various organs or systems of the body. It is estimated that over half of people with SLE have neuropsychiatric involvement.

Dipyaman Ganguly is an Indian immunologist and cell biologist, currently a Senior Scientist and Swarnajayanthi Fellow at the CSIR-Indian Institute of Chemical Biology (IICB). He heads the Dendritic Cell Laboratory of IICB, popularly known as Ganguly Lab, where he hosts several researchers involved in research on regulation of innate Immunity and pathogenesis of inflammatory disorders.

References

  1. Ramsey-Goldman, Rosalind; Li, Jian; Dervieux, Thierry; Alexander, Roberta Vezza (21 August 2017). "Cell-bound complement activation products in SLE". Lupus Science & Medicine. 4 (1): e000236. doi:10.1136/lupus-2017-000236. PMC   5704741 . PMID   29214038.
  2. Abulaban, Khalid M.; Brunner, Hermine I. (5 December 2014). "Biomarkers for Childhood-Onset Systemic Lupus Erythematosus". Current Rheumatology Reports. 17 (1). doi:10.1007/s11926-014-0471-2. PMC   4980820 .
  3. Ahearn, Joseph M.; Liu, Chau-Ching; Manzi, Susan (6 November 2017). "Cell-bound complement activation products as lupus biomarkers: diagnosis, monitoring and stratification". Expert Review of Clinical Immunology. 13 (12): 1133–1142. doi:10.1080/1744666X.2017.1392238. PMID   29025354.
  4. Wallace, Daniel; Hahn, Bevra Hannahs (27 September 2012). "Dubois' Lupus Erythematosus and Related Syndromes E-Book: Expert Consult - Online and Print". Elsevier Health Sciences via Google Books.
  5. "Exagen and the Lupus Foundation of America Partner on New Initiative to Reduce the Time to an Accurate Lupus Diagnosis". Lupus Foundation of America.