Abstract Body (Do not enter title and authors here): Introduction: Atherosclerosis displays all features of a chronic inflammatory disease, in which both cell - mediated and humoral immune responses participate. Instead of secondary lymphoid organs such as regional lymph nodes and spleen, local immune defenses against exogenous or intrinsic antigens are most likely carried out in tertiary lymphoid organs (TLOs) – lymph node-like immune cell clusters at the adventitial side of the arteries (Fig 1A-B). There are only a few human studies on the frequency of TLOs in coronary atherosclerosis and on their association with the severity of coronary heart disease (CHD).
Hypothesis: TLOs associate with the severity of CHD.
Methods: We studied the frequency of TLOs in 2142 histological sections from the left (LAD) and right (RCA) coronary arteries of 688 sudden out-of-hospital deaths of the Tampere Sudden Death Study (TSDS). The areas of atherosclerotic lesions were measured from fresh coronary specimens and stenosis percentage from microscopical sections of the coronary plaques using microscope and Olympus CellD morphometrical software. The presence of TLOs was studied in histological sections of the coronary arteries stained with van Gieson or MOVAT- Pentachrome.
Results: TLOs were detected in 190 (27.1%) of the coronaries of the victims. In logistic regression analysis with age and sex as confounding factors (Fig 1 C-D) their presence in coronary sections associated especially with larger calcified plaque area (LAD p<0.001, RCA p=0.002), larger atherosclerotic plaque surface area (LAD p=0.003; RCA p<0.001), with more severe coronary stenosis percentage (LAD p=0.008; RCA p<0.001) and with death due to fatal prehospital myocardial infarction (p<0.001) or CHD (p<0.001). The size of the TLOs varied and most were situated in the lamina adventitia or in the periadventitial fatty tissue. In some of the myocardial infarction cases, TLOs were also present in the media layer.
Conclusion: TLOs were frequently found in coronaries of victims who died of severe coronary heart disease with or without myocardial infarction and they may represent the end stage of chronic inflammation of coronary plaques due to immune response against intrinsic and/or extrinsic antigens such as oxidized LDL or bacteria.