Blood levels of the protein HMGB1 are elevated in children and adolescents with hemophagocytic lymphohistiocytosis (HLH), and higher levels are associated with clinical features of the disease, such as central nervous system involvement, a new study shows.
Titled “Serum high mobility group box protein 1 (HMGB1) levels reflect clinical features of childhood hemophagocytic lymphohistiocytosis,” the study was published in the Journal of Blood Medicine.
High mobility group box protein 1, known as HMGB1, is a protein with two functions. In healthy cells, it stays in the nucleus, bound to DNA, helping in gene activity. However, when cells become damaged, HMGB1 gets released into the blood, where it acts as a danger signal — sometimes called an alarmin — prompting the body’s immune system to become activated and driving inflammation.
“HMGB1 has been reported to be involved in the pathophysiology of various infectious and noninfectious inflammatory disorders,” the researchers said. However, its role in the hyperinflammatory disorder HLH has not been thoroughly studied.
To learn more, researchers in Japan measured the levels of HMGB1 in the blood of 28 children and adolescents with HLH (ages 10 days to 21 years, median age of 8.5 years), and of six healthy children without HLH (all aged 5), who served as controls.
Results showed that, compared with the controls, patients with HLH had significantly higher levels of HMGB1 in the blood — median 6.5 versus 0.25 ng/mL.
The team then assessed the participants’ medical records to determine whether the levels of this protein were associated with clinical features of HLH.
Of the 28 HLH patients, 10 (35.7%) had central nervous system (CNS) involvement — that is, the disease had an impact on their brain and/or spinal cord. On average, those with CNS involvement had significantly higher HMGB1 levels than those without (median 14.35 versus 5.4 ng/mL).
Additionally, 15 (53.6%) patients had disseminated intravascular coagulation (DIC), a condition in which clots form throughout the bloodstream and block small blood vessels. Those with DIC also had higher average HMGB1 levels than those without (median 11.0 vs. 4.5 ng/mL).
HMGB1 levels were not significantly associated with complications of the respiratory tract or with survival.
The researchers found that higher protein levels were significantly associated with higher levels of aspartate aminotransferase, a marker of liver and muscle damage, and with lower levels of fibrinogen, a clotting factor.
However, the team noted that these findings “must be interpreted cautiously because our sample size was small. Further study in a large cohort is needed to determine which parameters are correlated with HMGB1,” they said.
Because of its known role in inflammation — and because HLH is an inflammatory disease — the researchers speculated that the protein might play a role in the development of HLH.
“Serum HMGB1 levels reflect clinical features of childhood HLH. HMGB1 is a potential mediator involved in the pathogenesis and determining the clinical findings of HLH,” the researchers said.
Nonetheless, the team emphasized that more research is needed to confirm these findings.