Susceptibility for Rheumatoid Arthritis Acquired via Microchimerism?

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Women with RA ask why it’s so common to acquire severe Rheumatoid Arthritis after pregnancy the way I did. I don’t blame my son since my symptoms went back years, but these studies are fascinating…

Rheumatoid Arthritis HLA shared epitope may be acquired in pregnancy

depiction of Microchimerism & RAThe current issue of Arthritis and Rheumatism brings a study which concludes that “RA patients who genotypically lack the SE (shared epitope) can acquire the SE as persistent microchimerism from fetal-maternal cell exchange, suggesting that SE-encoding microchimerism could be a risk factor for RA.”

An abstract presented last November at ACR examined whether Rheumatoid Arthritis patients can acquire the shared epitope through Microchimerism. From the full study, in this month’s issue: “The quantity of SE microchimerism (microchimerism concentration) was higher in RA patients than in healthy women. Ranked values of microchimerism with the SE overall were significantly higher among women with RA than healthy women… In separate analyses for SE type, the ranked values of QKRAA microchimerism were also significantly higher among women with RA compared to healthy women… Similarly, ranked values of QRRAA microchimerism were significantly higher among women with RA.”

What is the Shared Epitope (SE)?

The shared epitope for Rheumatoid Arthritis is as genetic pattern that is common in RA patients, especially those with CCP antibodies or severe RA disease.

I found a free article on PLoS One which explains the shared epitope for Rheumatoid Arthritis: “The ‘shared epitope’ (SE) is a five amino acid sequence motif in positions 70–74 of HLA-DRβ chains encoded by HLA-DRB1 alleles that are strongly associated with susceptibility to severe rheumatoid arthritis (RA).”

What is Microchimerism?

One of the researchers, Dr. J.L. Nelson, has authored a site devoted to explaining Microchimerism (Mc).  He explains that genetic material can pass from mother to child or vice versa during pregnancy, contrary to what some of us were taught in college. Even opposite gender DNA can persist for decades. Dr. Nelson and other scientists have been studying how Mc may relate to autoimmunity.

“Fetal Mc may be beneficial during pregnancy in women with rheumatoid arthritis, as elevated levels significantly correlated with pregnancy-induced amelioration of arthritis.” They also believe it may also be involved in the development of RA since it was detected in Rheumatoid nodules. Their hope would be to either harness its protective tendencies or unlock the process by which may stimulate the onset of RA.

Male DNA in mom’s Rheumatoid Nodules via Microchimerism

We went to the intriguing poster session at the ACR meeting called “The Clinical Features of 13 Women with Microchimerism in Rheumatoid Nodules.” Rheumatoid nodules of 13 women with clinically severe RA disease were found to contain male DNA. We were amazed that there was an inverse relationship between the ACPA (anti-CCP) level and the amount of male DNA.

The SE (shared epitope) risk gene was positive in 10 of the 13 patients and 10 of the 13 sons. They concluded that there is a connection between Microchimerism (Mc) and “citrullination of the SE in the pathogenesis of RA” with a possible function for “microtrauma” and an inverse relationship with anti-CCP.

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Kelly Young. All rights reserved.

This entry was posted on Tuesday, March 8th, 2011 at 6:00 am and is filed under RA Research, Resources, and Rheumatology. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.


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