How pregnancy can affect Sjögren’s ectopic lymphoid structures

Take-home message: Investigators have found that pregnancy in a rabbit model can interact with stochastic phenomena that contribute to the formation of ectopic lymphoid structures (ELS) in Sjögren’s syndrome. However, counter-regulatory phenomena were also found that prevent cells from coalescing into ELS. With better understanding of the counter-regulatory mechanisms, it may be possible to prevent ELS from developing or to reverse the process, thus reducing the risk of Sjögren’s syndrome developing.

Reviewed by Austin K. Mircheff, PhD

Los Angeles-Research in an animal model has shown that pregnancy can increase accumulation and activation of cells and functions associated with ectopic lymphoid structures (ELS) in Sjögren’s syndrome. Further research on the mechanisms involved in the development of ELS as well as the counter-regulatory mechanisms that may prevent cells from coalescing into these structures could eventually lead to interventions that might prevent the development of Sjögren’s syndrome, said Austin K. Mircheff, PhD, professor, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles.

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Dr. Mircheff and colleagues have begun to explore an approach that can not only describe what is happening during pregnancy that could cause Sjögren’s syndrome later in life, but it also could discern potential therapeutic targets, although the work is in very early stages.

“It’s not just a way of visualizing the precursors of a disease process but also seeing what the biological mechanisms and signaling interactions  are between the various types of cells that have to organize themselves into rather complex structures and then interrupting the signals that are crucial to them finally coalescing,” said Dr. Mircheff.

Cells organizing and pregnancy

In earlier research, the researchers discovered a cluster of very strongly correlating transcripts in the lacrimal glands of rabbits. They mapped the transcripts conceptually or hypothetically to the different cell types that are likely to be producing them. The cells seemed to have organized themselves into a network resembling an ELS, Dr. Mircheff said, and many of the proteins the network transcripts specify are characteristic of Sjögren’s syndrome ELS. While all were present in normal glands in small amounts, the numbers varied, partly in relation to the climatic conditions under which the rabbits had been raised and partly in response to intrinsic, stochastic factors.

The team hypothesized that pregnancy might influence the development of the cellular network. They then conducted additional studies in which they tested six pregnant rabbits and six virgin rabbits using q-RT-PCR to determine the abundances of 62 transcripts in each lacrimal gland, and they used Pearson’s test to identify clusters of positively- and negatively-correlating transcripts.¹

When comparing the abundances from the lacrimal glands of pregnant rabbits and virgin rabbits for all of the transcripts in the network, there were few statistically significant differences.

“But what was obvious was that there was a hugely bigger range of variation among the glands from the pregnant animals than the glands from the virgin animals,” Dr. Mircheff said. “Then when we looked at the data more closely, we saw that the individual glands from the pregnant animals sorted into two clusters, one where all of these transcripts were higher than normal and another cluster where they were all lower than normal.”

This dichotomy has been confirmed with principal component analysis. 

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