THE TIN MAN GUIDE TO STIFF-PERSON SYNDROME
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Anti-nuclear antibodies (ANA) are autoantibodies that bind to contents of the cell nucleus. There are many subtypes of ANA: anti-RNA, anti-ENA, antinuclear Smith, antinuclear RNP, antihistidyl, antichromatin, antinucleosome, antihistones, anti-ds-DNA anti-ss-DNA, anti-SS-A (Ro), anti-SS-B- (Lo).


There are four patterns:


Homogeneous (diffuse) is associated with lupus and mixed connective tissue disease.


Outline pattern (peripheral)  is associated with lupus.


Speckled pattern is associated with lupus, scleroderma, Sjögren's syndrome, polymyositis, rheumatoid arthritis, and mixed connective tissue disease.


Nucleolar pattern is associated with scleroderma and polymyositis.


ANA titer and pattern are helpful in screening for autoimmune diseases, including lupus, scleroderma, Sjögren's syndrome, polymyositis, dermatomyositis, myasthenia gravis, leukemia, cirrhosis, rheumatoid arthritis, polyarteritis nodosa, mixed connective tissue disease, drug-induced lupus, and autoimmune hepatitis, or juvenile arthritis.


Sögren's antibodies (anti-SS-A, anti-SS-B) are used to diagnose Sögren's.


Antineutrophil cytoplasmic antibody (ANCA) are antigens that target cytoplasmic components neutrophils. It is used to screen for  Wegner’s granulomatosis, microscopy polyarteritis, idiopathic gromerulonephritis, ulcerative colitis, primary sclerosing cholangitis, autoimmune hepatitis, active viral hepatitis, and Crohn’s disease.


Myeloperoxidase antibodies (MPO) are antigens that attack myeloperoxidase which is expressed in neutrophil granulocytes (a subtype of white blood cells). MPO catalyzes the conversion of hydrogen peroxide to hypochlorite and hypochlorous acid. This test is used to screen for vasculitis and Wegener's granulomatosis.


Cryoglobulins are abnormal globulin protein complexes in the blood of patients with various diseases. It is used to screen for connective tissue disease (lupus, Sjögren's syndrome, rheumatoid arthritis, multiple myeloma, leukemia, lymphoma, acute and chronic infections, toxoplasmosis, cytomegalovirus, and liver disease.


Cyclic citrullinated peptide (CCP), or anti-CCP, target the bodiy’s citrullinated proteins. It appears early in patients with rheumatoid arthritis, sometimes before the rheumatoid factor.


Endomysial, gliadin, and tissue transglutaminase antibodies are made in the gut mucosa and serum of gluten sensitive patients.


Gliadin and gluten are proteins in wheat and wheat products and become toxic to the mucosa of the small intestine and cause pathologic lesions. These tests screen for celiac disease, sprue, and dermatitis herpetiformis.


IFA with reflex /  IFIQN: intrinsic factor antibodies are used to diagnose pernicious anemia, which is the primary cause of B12 deficiency.  Type 1 is a blocking antibody that prevents the binding of B12 and IF. Type 2 affects the binding of IF to the ileum.


Ganglioside antibodies include:


Ganglioside GD1a Antibody (IgG, IgM)

Ganglioside GD1b Antibodies (IgG, IgM)

Ganglioside GQ1b antibody (IgG)

Ganglioside GM-1 Antibodies (IgG, IgM)

Ganglioside Asialo-GM-1 Antibody (IgG)

Ganglioside Asialo-GM-1 Antibody (IgM)


These antibodies are found in autoimmune neuropathies, Guillain-Barré syndrome, dementia, rheumatoid arthritis, Sjögren's syndrome, and lupus.


Myelin associated glycoprotein antibodies (MAG) disrupt the function of myelin associated glycoproteins and damage Schwann cell production of myelin. This test is used to diagnose a MAG-related neuropathy.


Proteinase-3 antibody is a 29kD serine protease that exists as a protein triplet in human neutrophils. It is used to screen for Wegener granulomatosis.



Rheumatoid Factor measures IgM antibodies that are involved in an inflammatory process in synovial tissues, blood vessels, lungs, nerves, and heart. It is used to screen for rheumatoid arthritis, lupus, chronic viral infection, tuberculosis, chronic hepatitis, dermatomyositis, scleroderma, infections, mononucleosis, leukemia, cirrhosis, syphilis, and renal disease.


Ribosomal P antibodies are specific for lupus and have been reported in patients with central nervous system involvement. Most patients with lupus do not have detectable levels, but when they do central nervous system involvement is possible.


Anti-topoisomerase antibodies (ATA) are directed against topoisomerase and react with self-proteins. They are also referred to as anti-DNA topoisomerase I antibody (anti-topo I). This is test is used to screen for scleroderma.


Tissue transglutaminase antibodies (tTG) attack the transglutaminase protein and is used to screen for celiac disease, inflammatory bowel disease, arthritis, and juvenile diabetes.


Immunoglobulin A ((IgA) has two forms and is found in mucosal areas, such as the gut, respiratory tract, and urogenital tract, and prevents colonization by pathogens. It is also found in saliva, tears, and breast milk.


Increased IgA can indicate chronic liver disease, chronic infection, and inflammatory bowel disease. Decreased levels can point toward ataxia, nephrotic syndrome, treatment with immunosuppressive drugs, liver disease, rheumatoid arthritis, Sjögren's syndrome, lupus, and multiple myeloma,


Immunoglobulin D (IgD) acts mainly as an antigen receptor on B cells that have not been exposed to antigens. It has been shown to activate basophils and mast cells to produce antimicrobial factors.


In B cells, IgD's function is to signal the B cells to activate. IgD is expressed when B-cells exit the bone marrow to populate peripheral lymphoid tissues. When a B-cell reaches its mature state, it co-expresses both IgM and IgD


Immunoglobulin E (IgE) binds to allergens and triggers histamine release from mast cells and basophils. IgE defends against allergic diseases, such as asthma, most types of sinusitis, allergic rhinitis, food allergy, and some types of chronic urticaria and atopic dermatitis. IgE also plays a pivotal role in anaphylactic reactions to certain drugs, bee stings, and antigen preparations used in specific desensitization immunotherapy.


This test is useful in screening for allergic reactions, hay fever, asthma, and parasites.


Immunoglobulin G (IgG) has four forms and provides the majority of antibody-based immunity against invading pathogens.  It is the only antibody capable of crossing the placenta to give passive immunity to the fetus.


IgG binds to many pathogens such as viruses, bacteria, and fungi.


IgG activates a cascade of immune protein production that results in pathogen elimination. IgG also binds and neutralizes toxins. It can be a factor in many autoimmune diseases such as hemolytic anemia, thrombocytopenia, rheumatic heart disease, Goodpasture’s sundrome, Graves' disease, rheumatoid arthritis, post streptococcal glomerulonephritis, lupus nephritis, systemic lupus erythematosus, and myasthenia gravis, multiple myeloma, Sjögren's syndrome, and leukemia.


When patients are treated with IVIG, they are given IgG antibodies collected from the plasma of thousands of blood donors.


Immunoglobulin M (IgM) is expressed on the surface of B cells and in a secreted form (pentamer) with very high binding affinity. It is manufactured in the spleen and eliminates pathogens in the early stages of B cell-mediated immunity before there is sufficient IgG. IgM appears early in the course of an infection.


Activated B cells differentiate into either antibody-producing cells called plasma cells that secrete soluble antibody or memory cells that survive in the body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures. Memory cells are why some immunomodulating treatments fail. The circulating antigens are removed, but the memory cells are spared.


This test is useful in screening for chronic infections, hepatitis, chronic liver disease, nephrotic syndrome, multiple myeloma, and leukemia.


For more information on these tests, visit Quest Labs.

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