Background/Purpose:

The major source of naturally acquired microchimerisms (MC) is the transplacental traffic of fetal cells between a mother and the fetus during pregnancy. Fetal cells have been found to persist in maternal blood for many years post partum. It was the aim of this study to analyze the prevalence of fetal MC in patients with inflammatory rheumatic diseases and to investigate the association of MC with disease severity.

Methods:

A total of 143 women who had delivered at least one male offspring were recruited: 73 women with rheumatoid arthritis (RA), 16 women with systemic lupus erythematosus (SLE) and 54 women as non-affected controls. The mean age was 62.5 years (RA), 56.2 years (SLE), and 40.5 years (control cohort). Women who had received a blood transfusion in the past were not included in this study.

For the analysis of fetal MC in DNA from maternal circulation a nested PCR was used to detect a male fetal sequence in the TSPY gene on the Y chromosome.

For both disease groups age at disease onset and markers for disease activity were compared for MC+ and MC- patients, this includes for RA patients anti-CCP-antibodies (anti-CCP), rheumatoid factor (RF) and radiographic progression (Steinbrocker score); and for SLE antinuclear antibody (ANA) and anti-dsDNA antibody,  serum C3, C4, CH50, and soluble interleukin 2 receptor (sIL2R) levels.

Results:

The prevalence of fetal MC was 18% in RA patients and 31% in patients with SLE, which is significantly increased compared to 3.7% in non-affected controls (p=0.02 and p=0.006, resp.).

The mean age at disease onset was comparable in MC+ and MC- RA patients with about 43.3 years. Disease onset occurred 18.7 and 19.8 years post partum of the first son for MC+ and MC- patients, respectively. The presence of anti-CCP and RF did not differ significantly: anti-CCP were found in 75% of MC+ and 87% of MC- RA patients, RF in 75% of both MC+ and MC- patients. A higher mean Steinbrocker Score in MC+ patients (3.2 vs. 3.0) was associated with a longer disease duration: 19.4 years (MC+) vs. 16.5 years (MC-).

In SLE patients mean age at disease onset was 42.6 years in MC+ and 49.1 years in MC- patients. Disease onset occurred 24.0 and 26.4 years post partum of the first son for MC+ and MC- patients, respectively. The presence of ANA and anti-dsDNA antibodies, sIL2R, C3, C4, and CH50 did not differ significantly. In MC+ patients sicca symptoms were found most frequently (80%), followed by involvement of joints (60%), central nervous system (20%) and kidneys (20%). In contrast, in MC- patients joints were affected mostly (70%), followed by skin (60%), central nervous system (30%) and sicca symptoms (20%).

Conclusion:

In a cohort of RA patients as well as in patients with SLE the prevalence of MC was significantly increased compared to a cohort of non-affected controls. The disease severity in patients with RA or SLE did not differ depending on the presence of MC.

In conclusion our results indicate that the long persistence of microchimerism as a marker of a pathologic clearance of semi-allogeneic DNA is associated with rheumatic diseases without effect on disease severity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-fetal-microchimerisms-on-disease-onset-and-severity-in-women-with-rheumatoid-arthritis-and-systemic-lupus-erythematosus/