Background: The possible role of infectious pathogens in the development of thromboangiitis obliterans (TAO) was considered soon after the disease was first described. However, it is not yet known whether infectious pathogens induce thrombotic vasculitis or if they cause a type of autoimmune disease. To investigate whether TAO relapses are more likely due to reinfection or autoimmune flare, the serum levels of toll-like receptor (sTLR) 4, sTLR2, C-reactive protein (CRP), and neopterin were evaluated in TAO patients during both the acute and quiescent phases of the disease as well as in a gender-, age-, and smoking habit-matched control group.
Methods: Following a cross-sectional study design, 28 patients in the acute phase of TAO and 23 patients in the quiescent phase participated in this study. In addition, 31 matched controls were enrolled.
Results: Toll-like receptor (TLR) 4 was significantly higher in patients in the acute phase of the disease than in patients in the quiescent phase (P=0.012). Also, TLR4 was significantly higher in the patients with CRP >7 µm/mL than in the patients with lower CRP (P=0.031). Notably, TLR4 in the patients in the quiescent phase of TAO was significantly lower than in the controls (P=0.006). No significant difference in the level of TLR2 was found among the groups (P>0.05). Neopterin was significantly higher in the acute phase of TAO in comparison to the quiescent phase (P=0.003) and the controls (P=0.005).
Conclusion: These findings indicate that the trigger of TAO might be Gram-negative bacteria, which can be hidden or immunologically suppressed in the quiescent phase of TAO, leading to a lower level of TLR4 accompanying the normal level of neopterin. However, relapses might develop according to toxic or hypoxic cell injuries. Hence, TLR4 shedding will increase, and therefore, sTLR4 could become closer to the level demonstrated in the controls.
Keywords: Buerger’s disease; CRP; TLR2; TLR4; infection; innate immunity; neopterin; peripheral arterial diseases; thromboangiitis obliterans; vasculitis.