Levels of soluble TREM-1 in children with newly diagnosed type 1 diabetes and their siblings without type 1 diabetes: a Danish case-control study

Background: Type 1 diabetes (T1D) is an organ-specific autoimmune disease with an increase in incidence worldwide including Denmark. The triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory responses and has been linked to autoimmunity, severe psychiatric disorders, sepsis, and cancer.

Hypothesis: Our primary hypothesis was that levels of soluble TREM-1 (sTREM-1) differed between newly diagnosed children with T1D and their siblings without T1D.

Methods: Since 1996, the Danish Childhood Diabetes Register has collected data on all patients who have developed T1D before the age of 18 years. Four hundred and eighty-one patients and 478 siblings with measurements of sTREM-1-blood samples were taken within 3 months after onset-were available for statistical analyses. Sample period was from 1997 through 2005. A robust log-normal regression model was used, which takes into account that measurements are left censored and accounts for correlation within siblings from the same family.

Results: In the multiple regression model (case status, gender, age, HLA-risk, season, and period of sampling), levels of sTREM-1 were found to be significantly higher in patients (relative change [95%CI], 1.5 [1.1; 2.2],P = 0.02), but after adjustment for multiple testing our result was no longer statistically significant (P _adjust = 0.1). We observed a statistical significant temporal increase in levels of sTREM-1.

Conclusion: Our results need to be replicated by independent studies, but our study suggests that the TREM-1 pathway may have a role in T1D pathogenesis.