New research may show way to tell sarcoidosis from tuberculosis
Activation of immune B-cells may be key feature to distinguish 2 conditions
The activation of signaling pathways associated with immune B-cells may be a key feature that distinguishes sarcoidosis from tuberculosis, according to new research.
Both conditions are characterized by the presence of granulomas, or small clumps of inflammatory cells, and can have similar clinical manifestations, such as uveitis, a type of eye inflammation. That can make it difficult for people with these symptoms to get an accurate diagnosis — needed to ensure patients receive the correct treatment — the researchers noted.
Thus, the protein signature identified in this research could be “a key discriminative immunological feature” that helps distinguish the two conditions, the team wrote.
“Precise and timely diagnosis of [tuberculosis] and sarcoidosis are crucial since the two conditions are managed in distinct ways,” the scientists wrote.
The study, “A serum B-lymphocyte activation signature is a key distinguishing feature of the immune response in sarcoidosis compared to tuberculosis,” was published in the journal Communications Biology.
Investigating links between sarcoidosis and tuberculosis
Sarcoidosis is marked by granulomas that can form in any of the body’s tissues, most often the lungs. When sarcoidosis affects the eyes, it is known as ocular sarcoidosis.
It’s not exactly known how sarcoidosis arises, but it’s believed to involve a combination of genetic and environmental factors that drive abnormal immune activation.
Meanwhile, tuberculosis or TB, an infectious disease caused by Mycobacterium tuberculosis, also causes granulomas to form. It also usually affects the lungs, but can have ocular manifestations.
Both ocular sarcoidosis and ocular TB can manifest as uveitis, an inflammation in the middle layer of the eye. However, despite their clinical overlap, sarcoidosis and TB are treated differently, so establishing the right diagnosis is important, according to the researchers.
Finding reliable disease-specific biomarkers that align with the underlying disease-specific pathways in sarcoidosis and TB … is an urgent need.
While the two conditions have distinct cellular features that can be distinguished under a microscope, getting an ocular sample for analysis in a person with uveitis isn’t easy, among other diagnostic challenges, the team noted.
As such, “finding reliable disease-specific biomarkers that align with the underlying disease-specific pathways in sarcoidosis and TB … is an urgent need,” the researchers wrote.
To identify possible disease biomarkers, the team performed a protein analysis of blood samples from 90 sarcoidosis patients in the Netherlands and 22 people in Indonesia with active pulmonary TB. Among the sarcoidosis patients, 46 had uveitis, while 12 of those with tuberculosis had the eye condition.
Protein levels for each disease were compared with a group of geographically-matched healthy people, who served as control groups.
A number of common protein signaling pathways appeared to be activated in both disease states relative to their respective healthy control groups, including ones associated with inflammatory proteins, wound healing, and certain immune cell populations.
“Our findings highlight that … the two diseases exhibit significant overlap in the activation status of different biological pathways,” the researchers wrote, noting that the findings could possibly explain “the overlap in clinical manifestations between these diseases.”
More and larger studies needed for ‘unraveling’ the role of B-cells
Still, through a series of experiments, the researchers identified a possible signature of sarcoidosis that could distinguish it from TB. This was the excessive activation of a type of immune cell called B-cells. B-cells are responsible for producing antibodies that help the body fight off harmful invaders, but which can also underlie inflammatory and autoimmune diseases.
Specifically, the protein analyses indicated that B-cell activation pathways were more strongly linked to sarcoidosis than TB, including increased activity of two proteins — BAFF and APRIL — as well as a number of other related proteins that are important for B-cell maturation and survival.
Analyses of granuloma tissue from patients indicated that the areas surrounding sarcoidosis granulomas had more B-cells than those from TB patients.
While the findings overall point to a role for B-cells in sarcoidosis, the researchers pointed out that the exact role of these immune cells in the inflammatory disease is not established.
Further, certain treatments that work by depleting immune B-cells, including rituximab, are sometimes used to treat sarcoidosis that has not responded to standard therapy.
Overall there was no clear protein profile associated with the presence or absence of uveitis in either disease.
However, using an alternative approach, the researchers did identify a handful of proteins that might be able to distinguish sarcoidosis-associated uveitis from TB-associated uveitis. These proteins warrant additional study, the team noted.
The scientists noted as a study limitation that the findings were obtained from a single time point, and thus don’t account for how protein profiles might change over time in either disease.
Moreover, patients with the two diseases came from different geographical areas, which limited the ability to directly compare them.
“Further studies unraveling the role of [B-cells] in sarcoidosis and TB … are warranted,” the researchers wrote, noting that such studies should be larger and include patients from the same geographical region.
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