Lowered anti-beta1 adrenergic receptor antibody concentrations may have prognostic significance in acute coronary syndrome

Abstract

Although several risk factors exist for acute coronary syndrome (ACS) no biomarkers for survival or risk of re-infarction have been validated. Previously, reduced serum concentrations of anti-ß1AR Ab have been implicated in poorer ACS outcomes. This study further evaluates the prognostic implications of anti-ß1AR-Ab levels at the time of ACS onset. Serum anti-ß1AR Ab concentrations were measured in randomly selected patients from within the PLATO cohort. Stratification was performed according to ACS event: ST-elevation myocardial infarct (STEMI) vs. non-ST elevation myocardial infarct (NSTEMI). Antibody concentrations at ACS presentation were compared to 12-month all-cause and cardiovascular mortality, as well as 12-month re-infarction. Sub-analysis, stratifying for age and the correlation between antibody concentration and conventional cardiac risk-factors was subsequently performed. Serum anti-ß1AR Ab concentrations were measured in 400/799 (50%) STEMI patients and 399 NSTEMI patients. Increasing anti-ß1AR Ab concentrations were associated with STEMI (p = 0.001). Across all ACS patients, no associations between anti-ß1AR Ab concentration and either all-cause cardiovascular death or myocardial re-infarction (p = 0.14) were evident. However among STEMI patients ≤60 years with anti-ß1AR Ab concentration <median higher rates of re-infarction were observed, compared to those with anti-ß1AR Ab concentrations > median (14/198 (7.1%) vs. 2/190 (1.1%)); p = 0.01). Similarly, the same sub-group demonstrated greater risk of cardiovascular death in year 1, including re-infarction and stroke (22/198 (11.1%) vs. 10/190 (5.3%); p = 0.017). ACS Patients ≤60 years, exhibiting lower concentrations of ß1AR Ab carry a greater risk for early re-infarction and cardiovascular death. Large, prospective studies quantitatively assessing the prognostic relevance of Anti-ß1AR Ab levels should be considered.

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

“…This was demonstrated both for the autoantibodies to cell surface receptors [ 42 , 53 , 54 , 55 , 56 ] and for ANA [ 12 , 57 ]. For example, anti-DFS70 autoantibodies against the lens epithelium-derived growth factor are more prevalent in healthy people than in patients with ADs, and have been considered in recent years as an important marker of the lower probability of rheumatic diseases, even when the ANA test is positive [ 58 ].…”

“…Traditionally, it was assumed in diagnostic immunology that the more autoantibodies (either damaging or functional ones) a patient has, the more symptoms of the disease that will be present [62]. However, apparently, the level of some autoantibodies in a healthy individual should be no more, but no less than the optimum [53,63]. It has been suggested, by analogy with endocrine disorders which can equally occur both from excess and deficiency of a certain signaling molecule, that not only an increase, but also a pathological decrease in the concentration of autoantibodies may reflect and even cause pathological processes in the body [64].…”

Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease

“…Some autoantibodies are associated with a favorable outcome of the disease. This was demonstrated both for the autoantibodies to cell membrane receptors [42,[53][54][55][56] and for ANA [12,[57][58]. For example anti-DFS70 autoantibodies against the lens epithelium-derived growth factor are more prevalent in healthy people than in patients with ADs, and have been considered in recent years as an important marker of the lower probability of rheumatological diseases, even with ANA test being positive [59].…”

“…But, apparently, the level of some autoantibodies in a healthy individual should be no more, but no less than the optimum [53,63]. It has been suggested, by analogy with endocrine disorders which can equally occur both from excess and deficiency of a certain signaling molecule, that not only an increase, but also a pathological decrease in the concentration of autoantibodies may reflect and even cause pathological processes in the body [64].…”

What Makes Antibodies Against G Protein-Coupled Receptors so Special? A Novel Concept to Understand Chronic Diseases

“…Thus, patients with giant cell arteritis have lower ETAR ab levels compared to healthy donors (24) and patients with granulomatosis with polyangiitis have reduced levels of antibodies against complement receptors (2). Furthermore, reduced levels of antibodies against ß1-adrenergic receptors are present in patients with acute coronary syndrome and are associated with a more severe disease particularly with a higher risk for early reinfarction and cardiovascular death in patients ≤ 60 years (25,26). Lower abs against the thrombin receptor PAR-1 are associated with ovarian cancer and with high-grade carcinoma (2,27).…”