Assists in the early detection of connective tissue disorders, and in monitoring the effectiveness of related treatment protocols. This test evaluates arthritic peptide, collagen complex and fibulin, protein structures that indicate autoimmune reactivity.
Clinical Use
- Assist in the early detection of mixed connective tissue disorders
- Assist in monitoring the effectiveness of related treatment protocols
Recommended for Patients Who
- Have Arthritis or Arthralgias
- Have joint inflammation following exposure to environmental triggers
Antigens Tested (IgG + IgA Combined)
- Arthritic Peptide
- Collagen Complex
- Fibulin
Function Arthritic Peptide
Arthritic peptide, glucose-6-phosphate isomerase, is an endogenous molecule associated with joints. This cytoplasmic enzyme catalyzes the second step of glycolysis and is found at low levels in serum. Arthritic peptide can stimulate KRN T cells when processed and presented by antigen presenting cells.
Antibodies Appear:
- Mixed Connective Tissue Disease 1
- Osteoarthritis 2
- Rheumatoid Arthritis 1, 2, 3
Clinical Significance:
High levels of antibodies to arthritic peptide are found in patients with mixed connective tissue diseases including rheumatoid arthritis.1, 3 Musculoskeletal manifestations of Celiac disease include metabolic bone disease, muscle weakness, osteoarthritis, osteomalacia and polymyalgia rheumatic.2 Due to mucosal immune over-activation in rheumatoid arthritic patients, there is high cross-reactivity between joint tissues and foods, notably gluten, dairy peptides and pork.4 Thus, for better outcome with autoimmune arthritic patients, a tailored diet should be implemented.
References:
- Basu, et al. Molecular basis for the recognition of an arthritic peptide and a foreign epitope on distinct MHC molecules by a single TCR. J Immunol, 2000; 164:5788-5796.
- Bourne, et al. Arthritis and coeliac disease. An Rheum Dis, 1985; 44:592-598.
- Francis, et al. The prevalence of coeliac disease in rheumatoid arthritis. Eur J Gastroenterol Hepatol. 2002; 14:1355-1356.
- Hvatum, et al. The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis. Gut, 2006; 55:1240-1247.
Function Collagen Complex
Collagen is a group of proteins found in the flesh and connective tissues. The most abundant protein of the human body, Collagen is the main component of connective tissue. Collagen is found in tissues such
as tendon, ligament and skin, and is also abundant in cornea, cartilage, bone, blood vessels, the gut, and intervertebral disc. The fibroblast is the most common cell which creates collagen. In muscle tissue, collagen serves as a major component of the endomysium.
Antibodies Appear:
- Arthritis 4
- Goodpasture’s Syndrome* 1
- Type 1 Bullous
- SLE 3
Clinical Significance:
High levels of antibodies to Collagen Complex are noted in autoimmune arthritic disorders.3, 4 Circulating antibodies to collagen appear years before the clinical onset of arthritic conditions and is therefore considered an early biomarker or predictor of autoimmune arthritis.2
Blistering seen in bullous systemic lupus erythematosus may not always be widespread as shown by Fujii et al,3 they can develop on limited parts of the body. Circulating collagen antibodies demonstrate the involvement of an autoimmune mechanism.3
In a rat study, Arends et al. were able to show that infections with microbial peptides may induce antiglomerular basement membrane disease or Goodpasture’s syndrome through T cell epitope mimicry.*
References:
- Arends, et al. T cell epitope mimicry in antiglomerular basement membrane disease. J Immunol, 2006; 176:1252-1258.
- Dzhambazov, et al. Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide in complex with MHC class II molecules. J Immunol, 2006; 176:1525-1533.
- Fujii, et al. Detection of anti-type VII collagen antibody in Sjögren’s syndrome/lupus erythematosus overlap syndrome with transient bullous systemic lupus erythematosus. Br J Dermatol, 1998; 139:302-306.
- Khare, et al. Oral https://drhagmeyer.com/wp-content/uploads/2022/08/pexels-karolina-grabowska-5904094-1.pngistration of immunodominant human collagen peptide modulates collagen-induced arthritis. J Immunol, 1995; 155(7):3653-3659.
- Vojdani. A potential link between environmental triggers and autoimmunity. Autoimmune Dis, 2014; 2014:437231.
- Lundberg, et al. Periodontitis in RA – the citrullinated enolase connection. Nat Rev Rheumatol, 2010; 6(12):727-30.
- Ebringer, et al. Ankylosing spondylitis, HLA-B27 and Klebsiella – an overview: proposal for early diagnosis and treatment. Curr Rheumatol Rev, 2006; 2(1):289-297.
- Petković and Metlas. Cross-reactivity of the V3-specific antibodies with the human C1q. Z Naturforsch C, 2001; 56(11- 12):1135-1143.
- Werkmeister, et al. Characterisation of a monoclonal antibody against native human type I collagen. Eur J Biochem, 1990; 187:439-443.
- Sakaguchi,etal.ReactivityofIgEandIgGantibodiestohumancollagentype1inchildrenwithbovinegelatinallergy.JAllergy Clin Immunol, 2004; 113(2):S181.
Fibulin Function:
Fibulin is a calcium-binding glycoprotein found in blood and extracellular matrices. In the extracellular matrix, Fibulin associates with basement membranes and elastic fibers. This association with these matrix structures is mediated by Fibulin’s ability to interact with numerous extracellular matrix constituents including fibronectin, proteoglycans, laminins and tropoelastin. In blood, Fibulin binds to fibrinogen and incorporates into clots.
Antibodies Appear:
- Atherosclerotic Lesions 1
- Osteoarthritis 3
Clinical Significance:
Antibodies to Fibulin may be a contributing factor in the immunological pathways implicated in the pathogenesis of Osteoarthritis.3 To a lesser extent, anti-Fibulin antibodies were found in patients with Reumatoid Arthritis, Systemic Lupus Erythematosus and Systemic Scleroderma.3 Due to its characteristic of fibrinogen-binding,1, 2 Fibulin has been shown to play a role in the etiology and progression of cardiovascular diseases. Fibulin is a coagulation component of coronary artery atherosclerotic lesions.1, 2
References:
- Argraves, et al. Fibulin-1 and fibrinogen in human atherosclerotic lesions. Histochem Cell Biol, 2009; 132:559-565.
- Tran, et al. The interaction of fibulin-1 with fibrinogen: A potential role in hemostasis and thrombosis. J Biologic Chem, 1995; 270(33):19458-19464.
- Xiang, et al. Fibulin-4 is a target of autoimmunity predominantly in patients with osteoarthritis. J Immunol, 2006; 176:3196-3204.