Various antibodies in TAO have been reported, including anti-endothelial cell antibodies , anti-neutrophil cytoplasmic antibodies , anti-phospholipid antibodies , anti-cardiolipin antibodies , and agonistic auto-antibodies directly against the G-protein coupled receptor . TAO is associated with elevated cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-6, IL-17, and IL-23 [10, 11]. TAO is also associated with an increased expression of vascular cell adhesion molecules, intracellular adhesion molecules, and E-selectin on the endothelial cells of the affected arteries . Kobayashi et al.  reported IgG, IgA, IgM, and complement factors C3d and C4c deposit along the internal elastic lamina, and cell infiltration was observed in the thrombus and the intima of patients with TAO (CD3+ T cells greatly outnumbered CD20+ B cells, CD68+ macrophages or S-100+ dendritic cells). Fu et al.  found that TAO patients have low erythrocyte immune function, so the erythrocytes are less able to adhere to the circulating immune complex, and Cui et al.  found an immune complex deposit in the vessel wall under electron microscopy, which aligns with our findings .The evidence suggests TAO pathogenesis involves humoral and cellular immunity, with TAO vessel cell immune response activation, inflammation, damage, and thrombosis. Immunosuppressive agents suppress the immune response in TAO patients . The use of immunoadsorption to remove TAO antibodies from the blood showed promising results in the clinic [17, 18].
In the present study, TAO humoral immunology showed a highly significant increase in IgE. Combined with TAO clinical manifestations, repeated acute episodes, and the initiating factors (e.g. tobacco use, climate, trauma, and malnutrition) . It has long been recognized that persistent cigarette smoking is a major risk factor for TAO persistence, progression, recurrence, and amputation. TAO patients seem to be in a sensitized state to cigarette smoking, indicating the presence of a Type I allergy. Elevated IgE levels may play some role in the pathogenesis of TAO as an autoimmune disease , but this should be further explored for confirmation. Three types of immuno-labeling techniques all confirmed anti-vessel auto-antibodies in the sera of TAO patients. Furthermore, Ag-Ab complex deposits were observed directly on the vessel wall in multiple immune label samples. The existence of Type III hypersensitivity reaction was again confirmed. The auto-antibodies against the vessel were combined directly with damaged vascular collagen, which reflects a Type II hypersensitivity reaction (as noted in Figs. 4-6).
According to the etiology analysis in our previous study of 876 cases , cigarette smoking was the greatest factor, but we also found other factors closely related to the disease. Most patients (80%) had a history of exposure to dampness and sudden temperature changes (eg, intense exercise with sweating followed by freezing), and exposure to hot or cold extremes. 29% of patients had a history of trauma, and 70% of patients had a history of malnutrition. Also, 17% of TAO patients were not smokers but shared other risk factors as described above—risk factors that induce damage to the vessel walls to become auto-antigen or/and become sensitive factors to induce an allergic reaction. Cigarette smoking can not only introduce an allergic antigen, which may induce a Type 1 allergic reaction in TAO, but nicotine is also a hapten with blood red cells, intracellular histones or DNA binding, and therefore alters their composition, resulting in the production of auto-antibodies .
TAO shares many characteristics with autoimmune diseases. For example, TAO patients have autoantibodies and sensitized lymphocytes, high levels of r-globulin in serum ; deposition of the Ag-Ab complex in damaged vessels; and lymphocyte, plasma cell, and monocyte infiltration in the target vessels . TAO patients also have a variety of auto-antibodies, and TAO has a genetic component [21, 22]. In the clinic, patients with TAO often have repeated recurrences and chronic stability.stage In acute episodes of TAO, the course of the disease is managed using immunosuppressive agents  and immunoadsorption agents to remove TAO antibodies [17, 18]. TAO patients will sometimes experience damage to both extremities and viscera [23, 24], which indicates TAO may be a systemic autoimmune disease. Changes in sex hormones have an impact on immune function and may lead to autoimmune diseases. Although most autoimmune diseases occur in women, TAO is more common in men, suggesting that man hormones may play a role.