Characteristics of autoantibodies targeting 14-3-3 proteins and their association with clinical features in newly diagnosed giant cell arteritis.

Objectives: Autoantibodies are useful biomarkers for diagnosing and monitoring treatment in some autoimmune diseases. Antibodies against isoforms of 14-3-3 protein have been proposed as biomarkers for the presence of aortic aneurysm in large-vessel vasculitis (LVV). Here, we aimed to evaluate the diagnostic role and potential immunopathological involvement of anti-14-3-3 antibodies in newly diagnosed LVV patients. Methods: Antibodies against three isoforms of 14-3-3 (γ, ɛ and ζ) were measured in 90 subjects: 48 GCA and 3 Takayasu's arteritis (TA) patients, and 39 controls (non-inflammatory and inflammatory diseases), using a multiplexed bead-based immunoassay and immunoprecipitation studies. The positive cut-off value was defined based on young healthy controls. Anti-14-3-3 IgG antibodies in LVV patients were compared with those in controls in order to assess their diagnostic performance, and the relationship of anti-14-3-3 IgG antibodies to the immunohistopathology of artery explants was assessed. Results: Antibodies against all three 14-3-3 isoforms were detected in LVV patients as well as in age-matched inflammatory and non-inflammatory controls. Among LVV patients, detection of antibodies targeting 14-3-3 ɛ and ζ was associated with more severe disease. Detection of antibodies against 14-3-3 γ was linked to latent Toxoplasma gondii infection, a parasite that secrets a 14-3-3 homologue, suggesting potential cross-reactivity. Conclusion: Detection of antibodies against 14-3-3 proteins at the time of LVV diagnosis is not disease-specific. Their presence at high levels in LVV patients with stroke, aortitis and-in a previous study-aneurysm formation may indicate an association with extensive tissue destruction. The relevance of 14-3-3 antibodies in non-LVV patients needs to be investigated in larger cohorts.

Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine Levels.

BACKGROUND: Acute stress drives a 'high-alert' response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans. METHODS: 3,4-methylenedioxymethamphetamine (MDMA), methylphenidate (MPH), or both, were administered to healthy volunteers in a randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset frequencies, natural killer (NK) cell immune-phenotypes, and changes in effector function were assessed, and linked to stress hormone levels and expression of CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells. RESULTS: MDMA/MPH > MDMA > MPH robustly induced an epinephrine-dominant stress response. Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, but they expressed slightly reduced levels of the activating receptor NKG2D. Preferential circulation of mature NK cells was associated with high epinephrine receptor expression among this subset, as well as expression of integrin ligands previously linked to epinephrine-induced endothelial detachment. CONCLUSION: The acute epinephrine-induced stress response was characterized by rapid accumulation of mature and functional NK cells in the peripheral circulation. This is in line with studies using other acute stressors and supports the role of the acute stress response in rapidly mobilizing the innate immune system to counteract incoming threats.