Immunometabolic factors in adolescent chronic disease are associated with Th1 skewing of invariant Natural Killer T cells.

Invariant Natural Killer T (iNKT) cells respond to the ligation of lipid antigen-CD1d complexes via their T-cell receptor and are implicated in various immunometabolic diseases. We considered that immunometabolic factors might affect iNKT cell function. To this end, we investigated iNKT cell phenotype and function in a cohort of adolescents with chronic disease and immunometabolic abnormalities. We analyzed peripheral blood iNKT cells of adolescents with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (OB, n = 20), and corrected atrial septal defect (ASD, n = 25) as controls. To study transcriptional differences, we performed RNA sequencing on a subset of obese patients and controls. Finally, we performed standardized co-culture experiments using patient plasma, to investigate the effect of plasma factors on iNKT cell function. We found comparable iNKT cell numbers across patient groups, except for reduced iNKT cell numbers in JIA patients. Upon ex-vivo activation, we observed enhanced IFN-γ/IL-4 cytokine ratios in iNKT cells of obese adolescents versus controls. The Th1-skewed iNKT cell cytokine profile of obese adolescents was not explained by a distinct transcriptional profile of the iNKT cells. Co-culture experiments with patient plasma revealed that across all patient groups, obesity-associated plasma factors including LDL-cholesterol, leptin, and fatty-acid binding protein 4 (FABP4) coincided with higher IFN-γ production, whereas high HDL-cholesterol and insulin sensitivity (QUICKI) coincided with higher IL-4 production. LDL and HDL supplementation in co-culture studies confirmed the effects of lipoproteins on iNKT cell cytokine production. These results suggest that circulating immunometabolic factors such as lipoproteins may be involved in Th1 skewing of the iNKT cell cytokine response in immunometabolic disease.

Modulation of the cellular and humoral immune response to pediatric open heart surgery by methylprednisolone.

BACKGROUND: With the intention to reduce overshooting immune response, glucocorticoids are frequently administered perioperatively in children undergoing open heart surgery. In a retrospective study we investigated extensively the modulation of the humoral and cellular immune response by methylprednisolone (MP). METHODS: This study was carried out on blood samples from two groups of children who had undergone surgical correction of atrial or ventricular septal defects, either without (MP⁻, n = 10), or with MP administration (MP+, n = 23, dose median 11 (IQR 10-16) mg kg⁻¹ body weight) before cardiopulmonary bypass (CPB, duration median 42 (IQR 36-65) min). EDTA blood was obtained 24 h preoperatively, after anesthesia, at CPB begin and end, 4, 24, and 48 h after surgery, at discharge and at out-patient follow-up (median 8.2 (IQR 3.3-12.2) months after surgery). Complex blood analysis including clinical chemistry and flow cytometry were performed to monitor humoral immune response, differential blood count, lymphocyte subsets, and the degree of activation of various leukocyte subpopulations. RESULTS: The patients' postoperative courses and follow-up were uneventful. Release of IL-6 and IL8 was reduced and that of the anti-inflammatory cytokine IL-10 upregulated by MP. Significant increase of circulating neutrophils and monocytes as inflammatory reaction to surgery and CPB contact was detected in both groups. However, invasion of monocytes to the periphery was delayed with MP. CD4+ and CD8+ T-lymphocyte counts were lower with MP treatment. B-lymphocyte count increased significantly after surgery in MP+ but remained constant in MP⁻ group. CONCLUSIONS: MP treatment partially decreased the pro-inflammatory effect of CPB surgery and induced anti-inflammatory effect on the cellular and humoral level.

Antiphospholipid antibodies are common in patients referred for percutaneous patent foramen ovale closure.

Very little is known about any interaction between patent foramen ovale (PFO) and various hypercoagulable disorders that have been associated with cryptogenic stroke. Percutaneous PFO closure for secondary prevention of paradoxical thromboembolization is receiving increasing attention. Hypercoagulability may affect the potential risks and expected benefits of percutaneous PFO closure. Consecutive patients undergoing percutaneous PFO closure at a single center were screened for the presence of antiphospholipid antibodies, elevated lipoprotein(a), hyperhomocysteinemia, and dysfibrinogenemia. Sixteen of 34 patients (47%) with complete arterial hypercoagulability screening had laboratory evidence of arterial hypercoagulability. Thirteen of these patients (38%) had antiphospholipid antibodies. Antiphospholipid antibodies appear to be common in patients referred for percutaneous PFO closure for secondary prevention of systemic thromboembolic events. Thorough testing based on established recommendations is warranted. Further studies are needed regarding the interaction between PFO and various hypercoagulable disorders that have been associated with cryptogenic stroke.

[Effect of acupuncture-drug compound anesthesia on alteration of immune function in patients undergoing open-heart surgery].

OBJECTIVE: To observe the effect of electro-acupuncture (EA) on alteration of immune function of patients undergoing open-heart surgery with cardiopulmonary bypass (CPB), and to appraise the value of acupuncture-drug compound anesthesia in the operation. METHODS: Thirty patients undergoing atrial septal defect repairing operation were selected and divided into three groups, Group A was the general anesthesia group; Group B, the acupuncture anesthesia group and Group C, the general anesthesia plus EA group. Peripheral venous blood of patients was collected at different time points, i.e. before anesthesia, before CPB, 30 min and 24 hrs after CPB, to determine natural killer cells activity (NKCA), and the levels of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in supernatant of cell culture were also tested. RESULTS: NKCA was significantly lowered in Group A before CPB but increased in Group B, while no evident change was found in Group C, so the level of NKCA in Group B was significantly higher than in the other two groups. It lowered in all the three groups after CPB, especially evidently in Group B, so as to cause the NKCA level in Group B lower than that in Group A. The lowering further progressed, 24 hrs after CPB, NKCA in Group B was more reduced than that in Group C. Levels of IFN-gamma and IL-2 lowered in all the three groups after CPB, and further lowered at time point of 24 hrs after CPB, but the parameters in Group C were significantly higher than those in Group B. CONCLUSION: EA could enhance NKCA, but acupuncture anesthesia couldn't inhibit the suppressive effect of CPB on NKCA, IL-2 and IFN-gamma, suggesting that the immunosuppression induced by stress has a prior effect. General anesthesia plus EA yielded better effect than general anesthesia and acupuncture anesthesia, but it could't improve the immunosuppression completely, indicating that the compound anesthesia could partially improve the immunosuppression induced by CPB.

The observation of complement activation and polymorphonuclear neutrocytopenia during cardiopulmonary bypass.

By determining the plasma levels of C2, C4, factor B and polymorphonuclear neutrophils (PMNs) of the patients who received CPB, the path of complement activation and changes of PMNs were studied. The results suggest that complement system was activated through alternative pathway during CPB and was activated through classic pathway after CPB. The anaphylatoxin, the products of complement activation may be responsible for the polymorphonuclear neutrocytopenia.