Keywords auloanlibody thyroid peroxidase epitope autoimmunity chronic thyroiditis SUMMARY A significant percentage (64%) of healthy subjects was found to contain anti-thyroid peroxidase (TPO) antibodies in their sera. However, in contrast with IgG from sera of patients with chronic thyroiditis, IgG from sera of healthy subjects did not inhibit TPO activities both in guaiacol and iodide assays. In addition, anti-TPO antibodies from healthy subjects did not block the inhibition of enzyme activities by anti-TPO antibodies from patients. These findings suggest that anti-TPO antibodies from healthy subjects do not bind to the epitopes relating to substrate-combining sites of TPO. Thus, the specificities of anti-TPO antibodies in healthy subjects may differ from those in eases of chronic thyroiditis.

Abstract. The IgG subclass distribution of anti-thyroid peroxidase (TPO) antibodies in patients with chronic thyroiditis and in healthy subjects has been investigated. Anti-TPO antibodies in sera of patients with chronic thyroiditis were predominantly associated with IgGI, with a lesser contribution by IgG4 and IgG3. In contrast, anti-TPO antibodies of healthy subjects were exclusively associated with IgG4. Since structural differences in IgG subclasses reflect differences in their biological roles, these findings suggest that the role of anti-TPO antibodies in patients may differ from that in healthy subjects.

Background: Anlotinib demonstrated improved overall survival (OS) and progression-free survival (PFS) compared with placebo as a third-line or subsequent therapy in patients with non-small cell lung cancer (NSCLC) in the ALTER0303 trial. The status of epidermal growth factor receptor (EGFR) mutation, different previous treatment may affect the efficacy of subsequent therapy, and we did this subgroup analysis to characterize the efficacy of anlotinib in patients with and without EGFR mutation.Methods: The ALTER0303 trial was a randomized, double-blind, phase 3 study of anlotinib in patients with NSCLC who failed at least 2 lines of treatment. In the study, 138 of 437 randomized patients were EGFR mutation positive. A Cox model was used to examine the influence of previous treatment on the efficacy of anlotinib according to EGFR mutation status.Results: For patients with EGFR mutation, the OS was 10.7 and 6.3 months (HR 0.59; 95% CI: 0.38-0.94, P=0.025) in the anlotinib and placebo group, respectively. The PFS was 5.6 and 0.8 months (HR 0.21; 95%

Chlorella extract CE has been shown to induce production of T helper-1 cytokines, and regulate serum IgE levels in animal models of asthma. We aimed to evaluate whether CE could inhibit ovalbumin OVA-induced airway hyperresponsiveness AHR and airway remodeling in a murine model of asthma. Balb/c mice were allocated to four groups : a control group no OVA exposure, not given CE , a CE group no OVA exposure, given CE , an asthma group sensitized/challenged with OVA, not given CE and a CE asthma group sensitized/ challenged with OVA, given CE. In the asthma and CE asthma groups, mice were sensitized with OVA on day 0 and day 12, and then challenged with OVA on three consecutive days. In the CE and CE asthma groups, the mice were given feed containing 2 CE. We assessed AHR to methacholine, and analyzed bronchoalveolar lavage uid BALF , serum, lung tissue and spleen cells. Administration of CE was associated with signi cantly lower AHR in OVA-sensitized and challenged mice. CE administration was also associated with marked reduction of total cells, eosinophils and T helper-2 cytokines IL-4, IL-5 and IL-13 in BALF. In addition, administration of CE signi cantly decreased the numbers of periodic acid-Schiff PAS-positive cells in OVA-sensitized and challenged mice. Administration of CE also directly suppressed IL-4, IL-5 and IL-13 production in spleen cells of OVA-sensitized and challenged mice. These results indicate that CE can partly prevent AHR and airway remodeling in a murine model of asthma.

RATIONALE: Cysteinyl leukotrienes (cysLTs) facilitate mucosal type 2 (eosinophilic) immunopathology, especially in aspirin-exacerbated respiratory disease (AERD), by incompletely understood mechanisms. Leukotriene C 4 (LTC 4) acts at platelet-and epithelial-associated type 2 cysLT receptors (CysLT 2 R) to modulate eosinophilic airway inflammation. Because platelets constitutively express IL-33 protein, which is essential to the induction of type 2 immunopathology and aspirin sensitivity, we sought to determine whether platelets, activated through CysLT 2 R, cause IL-33dependent immunopathology. METHODS: Prostaglandin E 2 synthase deficient (Ptges-/-) mice were primed with house dust mite extract, and then were challenged with lysine aspirin (Lys-ASA) for lung function and mediator measurement. Lung IL-5, IL-13, and IL-33 were measured by ELISA. Intrapulmonary platelet recruitment was determined by histological staining and western blotting for CD41. RESULTS: Challenges of AERD-like Ptges-/mice with inhaled Lys-ASA elicited LTC 4 synthesis and caused rapid intrapulmonary platelet recruitment, accompanied by rapid increases in lung IL-33, IL-5, and IL-13. Platelet depletion and blockade of CysLT 2 R eliminate all manifestations of Lys-ASA challenges, including mast cell activation, changes in airway resistance, and increases in IL-33, IL-5, and IL-13. CONCLUSIONS: Platelets are essential to the CysLT 2 R-driven type 2 respiratory immunopathology and IL-33-dependent aspirin sensitivity. Antiplatelet medications may be useful to treat AERD and other disorders associated with type 2 immunopathology.