Rheumatic diseases, such as rheumatoid arthritis (RA), lupus and multiple sclerosis, are caused by autoimmune responses. While in immune deficiency disorders the immune system fails to elicit the appropriate immune responses, in autoimmune disorders the immune system overresponds against one’s own antigens. This failure to distinguish between self and nonself arises from breach of immune tolerance, the preventative mechanisms the immune system has in place to prevent attacking itself.1 Autoimmunity could affect specific organs (RA) or they could be systemic (lupus). Some diseases such as ankylosing spondylosis are considered both autoimmune as well as inflammatory arthritic diseases.
Examples of rheumatic diseases
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation and damage of the joints throughout the body, including hands and feet and affects about 0.5–1% of the population, being more common among women than men in the United States.2 Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. It affects multiple organ systems, such as the skin, kidneys, lungs and the central nervous system, by producing autoantibodies.3 Ankylosing spondylosis (AS) is a chronic, progressive inflammatory rheumatic disease of the axial musculoskeletal system caused by multiple genes.4
Genetic basis of AS
Genetic factors contribute significantly to rheumatological disease. In particular, the human leukocyte antigen (HLA) locus accounts for about 50% of genetic predisposition to rheumatological disease, with strong involvement of HLA-DRB1, a major histocompatibility complex (MHC) class II molecule.4 Other non-HLA susceptibility genes, such as protein-arginine deiminase type 4 (PADI4) and interleukin-2 receptor subunit α, are also implicated in rheumatological disease. HLA-B27, an MHC class I molecule, has a strong association with AS. HLA-B27 testing is routinely used to screen for ankylosing spondylitis.5,6
BD Biosciences tool for rheumatic disorders
BD Biosciences provides a tool for screening the presence of HLA-B27 antigen on lymphocyte surfaces. The presence of HLA-B27 is strongly associated with ankylosing spondylitis, a rheumatic disorder. The BD® HLA-B27 Kit offers rapid detection of HLA-B27 antigen expression in erythrocyte-lysed whole blood using BD flow cytometry systems.
Precision Table
| Precision | SD of LMF |
|---|---|
| Within Run | 0.7 |
| Between Instruments | 1.3 |
| Between Days | 0.8 |
| System Total | 1.5 |
The precision of the BD FACSCanto™ System was estimated using ten samples, five positive samples and five negative samples, for the HLA-B27 antigen. Samples were run in duplicate for two days, two runs each day, using three BD FACSCanto™ instruments and three operators. The SD for the mean of the values for HLA-B27 FITC LMF for each of the variables was calculated.
Cross-reactivity characterization
The anti–HLA-B27 antibody, clone GS145.2, used in the BD® HLA-B27 Test, has been shown to cross-react most commonly with HLA-B7.7 The LMF for some cross-reacting samples can fall on the positive side of the decision marker, thus resulting in false-positive results. A study was performed to characterize this cross-reactivity. Twenty-nine samples with known HLA-B cross-reactive antigens and six HLA-B27–positive samples, as determined by cytotoxicity or low-resolution molecular testing, were stained in triplicate and acquired by each of three operators on two BD FACSCanto™ instruments.
All six of the confirmed HLA-B27–positive specimens were above the decision marker. The five false-positive specimens were predominately HLA-B7.
References
- Wang L, Wang F, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015;278(4):369-395. doi: 10.1111/joim.12395
- Hunter TM, Boytsov NN, Zhang X, Schroeder K, Michaud K, Araujo AB. Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004-2014. Rheumatol Int. 2017;37(9):1551-1557. doi: 10.1007/s00296-017-3726-1
- Baechler EC, Batliwalla FM, Karypis G, et al. Interferon-inducible gene expression signature in peripheral blood cells patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-2615. doi: 10.1073/pnas.0337679100
- Chung IM, Ketharnathan S, Thiruvengadam M, Rajakumar G. Rheumatoid arthritis: the stride from research to clinical practice. Int J Mol Sci. 2016;17(6):900. doi: 10.3390/ijms17060900
- Dakwar E, Reddy J, Vale FL, Uribe JS. A review of the pathogenesis of ankylosing spondylitis. Neurosurg Focus. 2008;24(1):E2. doi: 10.3171/FOC/2008/24/1/E2
- Chen B, Li J, He C, et al. Role of HLA-B27 in the pathogenesis of anlkylosing spondylitis. Mol Med Rep. 2017;15(4):1943-1951. doi: 10.3892/mmr.2017.6248
- Levering WHBM, Wind H, Sintnicolaas K, Hooijkaas H, Gratama JW. Flow cytometric HLAB27 screening: cross-reactivity patterns of commercially available anti-HLA-B27 monoclonal antibodies with other HLA-B antigens. Cytometry B Clin Cytom. 2003;54(1):28-38. doi: 10.1002/cyto.b.10022
The BD® HLA-B27 System is a qualitative two-color direct immunofluorescence method for the rapid detection of HLA-B27 antigen expression in erythrocyte-lysed whole blood (LWB) using the BD FACSVia™, BD FACSCanto™, BD FACSCalibur™, BD FACSort™ or BD FACScan™ Flow Cytometers.
Not for use in tissue typing.
The BD FACSCanto™ Flow Cytometer is for In Vitro Diagnostic Use for up to six colors. Seven to ten colors are for Research Use Only.
For In Vitro Diagnostics Use.
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