The data underscore the fact that “We need to take a broader view on what a normal functional immune system is,” emphasized Dr. Zalocusky.
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Example: The 10,000 Immunomes Project made it possible to power a pregnant-woman analysis. When they performed this analysis, the investigators found that, during pregnancy, women have a distinct immunological profile when compared with a matched population of non-pregnant women. The results are especially significant in the first trimester, when pregnant women experience a large shift in cytokine expression. The analysis also revealed a pro-inflammatory response from CD4+ T cells and a concomitant anti-inflammatory response from natural killer cells during the first trimester of pregnancy.
The researchers hope the 10,000 Immunomes Project can help advance precision immunology by serving as a source of references that can be used as common controls for comparison with molecular and cellular immune system responses in specific populations.
Single-Cell Gene Expression in RA
Theresa L. Wampler Muskardin, MD, a rheumatologist and pediatrician at the Mayo Clinic Inflammatory Arthritis Clinic in Rochester, Minn., presented results from the first study to examine gene expression in single monocytes from patients with seropositive rheumatoid arthritis (RA) prior to treatment.2 The investigators hope their work will help the development of a more individualized approach to therapy in patients with RA.
Researchers found marked differences in the ratio of expression of interferon (IFN) β/α genes in monocytes of patients with RA. Specifically, a ratio >1.3 of IFN β to IFN α predicted nonresponse to anti-tumor necrosis α (anti-TNFα) therapy. When the investigators analyzed each monocyte subset separately, they identified distinct expression signatures that suggested that further study of monocyte subsets may illuminate molecular differences that determine treatment response to anti-TNFα therapy in these patients.
Response to Infection
Darragh Duffy, PhD, research manager at the Institute Pasteur in France, presented his team’s work on the effect of age, sex and genetics on transcriptional immune responses to bacterial, viral and fungal challenges.3 The researchers hope their results will lay a foundation for new patient stratification strategies that consider the effects of age, sex and genetics on variable immune response outcomes. The investigators found that age affects gene expression in a stimuli-specific manner and that sex had a similar effect across all challenges.
Their analysis identified hundreds of expression quantitative trait loci that were regulated in both cis and trans manners for all stimuli-induced responses. They also confirmed the presence of a toll-like receptor 1 master regulator that has recently been shown to be an important factor that controls variable immunity in European populations. The investigators were able to integrate this transcriptomic and cellular data in a model that describes how age and sex mediate their effects through different immune populations.