Chemical Messenger CCL28 May Be Promising Biomarker for Sjögren’s
Levels of the chemical messenger CCL28 are reduced in the blood of people with primary and secondary Sjögren’s syndrome, and were correlated with oral disease features like dental cavities and salivary gland damage, according to a recent Chinese study.
Additionally, blood count changes — also lower — were linked to CCL28, adding to knowledge about the chronic autoimmune disorder.
Similar changes were not observed among patients with other autoimmune conditions, suggesting that CCL28 may serve as a promising and specific biomarker for Sjögren’s, the researchers noted.
The study, “Serum CCL28 as a biomarker for diagnosis and evaluation of Sjögren’s syndrome,” was published in the Scandinavian Journal of Rheumatology.
Sjögren’s is an autoimmune condition characterized by the body’s mistaken immune attack on its own moisture-producing glands. The salivary glands are one of the most affected, leading to a lack of saliva production, dry mouth, and oral disease.
CCL28 is a chemokine — a type of protein involved in orchestrating the movement of immune cells via chemical signals. It mediates immunity by promoting the movement of antibody-expressing cells to several tissues, including the salivary glands.
Levels of this chemical messenger are decreased in the saliva of Sjögren’s patients, suggesting that it could be used as a biomarker, particularly for oral disease manifestations.
Since many patients lack saliva due to damage to the salivary glands, it is of importance to understand how CCL28 levels in the serum — the fluid component of blood — relate to Sjögren’s, the research team noted.
To address this, they evaluated CCL28 levels in the serum of 35 people with primary Sjögren’s and 25 people with Sjögren’s secondary to other autoimmune conditions, namely rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). The study involved 11 people with RA and 14 with SLE.
Also included were 18 people with RA only, 10 with SLE only, and 24 healthy volunteers.
Researchers observed that serum levels of CCL28 were in general lower in Sjögren’s patients — including those with primary and secondary disease — than healthy participants. Specifically, the levels were a median of 700.3 picograms per milliliter (pg/mL) versus 1,246 pg/mL.
Individuals with Sjögren’s secondary to RA or SLE had markedly diminished CCL28 levels compared with those who had RA or SLE alone. CCL28 levels were comparable between patients with RA, SLE, and healthy individuals, who served as controls.
When comparing the relationship between CCL28 levels and clinical Sjögren’s features, including dry mouth, dry eyes, dental cavities, and arthritis, researchers found that levels of the chemical messenger tended to be lower in Sjögren’s patients who had cavities than in those without.
CCL28 has some anti-bacterial properties, which could explain an increase in cavities among those with low levels of the protein, the researchers hypothesized.
Sjögren’s can sometimes present with changes in the blood, including a reduction in platelet counts — a condition known as thrombocytopenia. The team found that patients with thrombocytopenia also had lower CCL28 levels.
“Thrombocytopenia secondary to [Sjögren’s] is a complication that is difficult to treat clinically,” the team wrote.
“Exploration of the relationship between the two and further studies on the relevant mechanism may lead to a new therapeutic target for thrombocytopenia,” they added.
Images of cells from the salivary glands of a few patients showed that reduced CCL28 levels were associated with a greater degree of injury to the glands. Such data indicate that CCL28 could possibly be a marker of Sjögren’s severity, the team said.
CCL28 normally binds to the CCR10 receptor to recruit IgA antibody-secreting cells, which are an important component of immune responses. Given this relationship, researchers hypothesized that IgA levels also would be impaired or dysregulated in Sjögren’s patients.
While IgA levels were significantly increased among Sjögren’s patients compared with healthy individuals, these levels did not correlate with CCL28, which, the team noted, could be explained by the fact that IgA has several sources in the body.
Previous studies have shown that in contrast to the decrease observed in Sjögren’s, CCL28 is elevated in several other autoimmune conditions. According to the team, this means that the protein may be a useful biomarker for distinguishing Sjögren’s from other autoimmune disorders.