Immune NKT Cells May Suggest Early Heart Involvement
The blood levels of natural killer T-cells (NKT), a type of immune cell, are reduced significantly in sarcoidosis patients with subclinical signs of heart involvement relative to those without, a small study shows.
Notably, low NKT cell levels were associated significantly with imaging markers of heart inflammation, suggesting that these cells may be used as an early biomarker of heart involvement in sarcoidosis patients.
Larger studies are needed to confirm these findings and the diagnostic potential of NKT cells in this patient population, the researchers said.
The study, “Peripheral blood natural killer cells in sarcoidosis are associated with early cardiac involvement,” was published in the European Journal of Clinical Investigation.
In sarcoidosis, an overactive immune system leads to the formation of small clumps of inflammatory immune cells, called granulomas, in different tissues and organs, ultimately affecting how well they work.
About 20–25% of sarcoidosis patients are estimated to have subclinical, or asymptomatic, heart involvement (cardiac sarcoidosis), with only about 5% of patients developing symptoms.
Cardiac magnetic resonance imaging (CMR), also known as cardiac MRI, is a non-invasive imaging test that allows the assessment of heart function and structure.
Since it can discriminate between inflammation-related abnormalities and those associated with tissue scarring, CMR is “considered a promising diagnostic modality for early detection of clinical or sub-clinical cardiac Sarcoidosis,” the researchers wrote.
“Given the life-threatening nature of [cardiac sarcoidosis], it is pivotal to identify cardiac involvement on initial diagnostic evaluation through simple and easy to perform screening procedures to provide treatment when deemed necessary,” the researchers wrote.
A previous study suggested that significantly lower counts of T-cells and B-cells — immune cells that fight against infections — in the blood were linked to severe organ involvement in sarcoidosis patients.
Now, a team of researchers in Greece evaluated potential associations between immune cell subsets in the blood and heart involvement in 85 adults newly diagnosed with sarcoidosis from two separate clinics.
Patients’ mean age was 50.5 years and all underwent cardiac investigation including CMR. Blood samples were collected to measure the number and proportion of several immune cells, including different subsets of T-cells, natural killer (NK) cells, and natural killer T-cells.
NK cells are part of the body’s first line of defense against infections and cancer, and are typically associated with pro-inflammatory responses. NKT cells comprise a unique subset of immune cells with features of both T- and NK cells and that have been shown to have both pro-inflammatory and immunosuppressive effects.
Notably, NKT cells were found to accumulate in the lungs of people with lung sarcoidosis, suggesting that they may boost “the inflammatory activity in the lungs,” the team wrote.
Results showed that heart involvement was present in 19 patients (23.5%). These patients showed significantly lower numbers and proportions of NKT cells in the blood relative to those without heart involvement. No significant group differences were detected in the other immune cells.
Notably, the absolute numbers of NKT cells in the blood were found to distinguish, with some level of certainty, patients with heart involvement from those without signs of cardiac sarcoidosis.
In addition, among patients with heart involvement, low blood counts of NKT cells were associated significantly with greater CMR signs of inflammatory lesions. This suggested these immune cells may be involved in the “inflammatory process of the heart,” the researchers wrote.
The number of NKT cells showed no significant link with severity of lung involvement in the whole group of patients.
These findings highlighted that low NKT cell counts in the blood of sarcoidosis patients “is associated with cardiac involvement, and the number of NK-T cells correlates with CMR findings indicative of [heart muscle] inflammation,” the team wrote.
While the data suggest that NKT cell depletion in the blood is due to their accumulation in inflamed tissues — where they may be driving immune responses that lead to granulomas — a true immunological deficiency also may explain these findings, the team noted.
Overall, these findings “might have clinical application as a screening strategy to detect clinically silent cardiac involvement in sarcoidosis and may also suggest potential targets for therapeutic interventions,” the researchers wrote.