An acquaintance of mine (45 year old, female) had a sudden onset of pain and swelling in one knee. Three doctors later, a rheumatologist finally diagnosed her with reactive arthritis. As an affirmation of the diagnosis, her blood was tested for the human leukocyte antigen B27 (HLA-B27), a MHC Class I molecule. She tested positive. About 3 weeks prior to this onset, on the way home from an international trip, she came down with a nasty GI bug, ultimately requiring antibiotics… seemingly unrelated, right? Wrong. The presence of HLA-B27 doesn't necessarily mean a person will develop reactive arthritis, rather that there is an increased risk of developing it upon exposure to specific bacteria. Painful arthritis involving joints of the lower extremities generally begins within a month of the initial infection in the majority of patients.
There are conflicting theories as to the involvement of HLA-B27 in these immune responses; one describes an autoimmune response subsequent to an initial response mounted against an infectious agent. Many cases, particularly those of reactive arthritis and uveitis, follow infection with gram-negative organisms, especially in the gut. Animal models support this theory. Subsequent cross-reactivity with HLA-B27, encoded by the B locus of the major histocompatibility complex (MHC) on chromosome 6, occurs due to similar epitopes between HLA-B27 and the infectious agent. As we have learned, Class I molecules are present on all nucleated cells and present antigen to CD8 T cells.
There are a number of inflammatory diseases associated with HLA-B27 and its prevalence varies significantly in the population from 0.1% of people of Japanese decent to 24% of those from northern Scandinavia. Over 100 disease associations have been made including ankylosing spondylitis, reactive arthritis, inflammatory bowel disease, and psoriatic arthritis.
Treatment includes NSAIDs, local administration of corticosteroids, physical therapy for posture maintenance and diet management in order to minimize the potential for developing a chronic problem. It is unclear whether antibiotics are helpful. A year later, the individual I spoke about still wrestles with pain and swelling in her knees and lower back. Diet alterations, physical therapy and acupuncture have provided her the most relief.
http://www.jbc.org/content/285/50/39180.abstract
http://www.nlm.nih.gov/medlineplus/ency/article/003551.htm
http://en.wikipedia.org/wiki/HLA-B27
what is the normal job of HLA-B27? I assume that its involvement in these afflictions is secondary to it's role in the body.
ReplyDeleteSo there are four theories offer us how HLA-27 cause spondyloarthritis: 1) HLA-B27 presents a ‘arthritogenic peptide’ that derived from bacteria; (2) a misfolding of HLA-B27 heavy chains causing a pro-inflammatory response; (3) individuals with HLA-B27 have arthritogenic organisms intracellular killing deficiency: and (4) HLA-B27 becomes autoantigenic, because it has the sequence homology with bacterial proteins. In fact, this give us an interesting inquiry for the discovery.
ReplyDeleteWell, in general HLA it self are proteins that help our immune system to differentiate the own cells and foreign or harmful substances.
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