Immune Profiles to Detect Heart Recipients at Risk of Development of Severe Infection

Abstract

Regulatory T cells (Tregs) were identified several years ago and are key in controlling autoimmune diseases and limiting immune responses to foreign antigens. Imaging of the human sodium/iodide symporter via Single Photon Emission Computed Tomography (SPECT) has been used to image various cell types in vivo . This study addresses whether SPECT/CT imaging can be used to visualise the migratory pattern of Tregs in vivo . Murine Treg lines were retrovirally transduced with a construct encoding for the human Sodium Iodide Symporter (NIS). NIS expressing self-specific Tregs were specifically radiolabelled in vitro with Technetium-99m pertechnetate ( 99m TcO 4- ) and exposure of these cells to radioactivity did not affect cell viability, phenotype or function. In addition adoptively transferred Treg-NIS cells were imaged in vivo in mice by SPECT/CT using 99m TcO 4- . After 24-hours Treg-NIS cells were observed in the spleen and their localisation was further confirmed by organ-biodistribution studies and flow cytometry analysis. Moreover, we have demonstrated that this method of imaging can be utilised to image migration of Tregs with direct and indirect allo-specificity in a skin transplant model. The data presented here suggests that SPECT/CT can be utilised in preclinical imaging studies of adoptively transferred Tregs without affecting Treg function and viability thereby allowing longitudinal studies within disease models. study. heart Clinical follow-up: 6 months. intravenous antimicrobial therapy, with positive clinical compromise. Study points: pre-trasplant, day-7 and day-30 after transplant. The immunological study included humoral and cellular immunity markers of : adaptive and innate immunity: Serum IgG, IgA, IgM, IgG subclasses, C3, C4, factor B (Nephelometry), manose binding lectin (ELISA), specific antibodies after vaccination (anti-pneumococcal polysaccharide [anti-PPS], anti-HBs, [ELISA]), natural specific antibodies without vaccination (anti-cytomegalovirus, anti-haemophilus influenzae type B, anti-salmonella typhi, anti-varicella zoster and T, B, NK lymphocyte subsets (flow-cytometry). Results: 154 patients were analysed. (38.3%) severe infections during follow-up. Univariate single marker analysis: Patients who disclosed: Lower levels of IgG (day 7, p< 0.001), C4 (day 7, p=0.016), IgG (day 30, p=0.007), IgA (day 30, p=0.016), anti-PPS (day 30, p=0.003) and lower absolute counts of NK CD3-CD16/CD56+ (day 7, p=0.017), T-CD3+ (day 30, p=0.008), T-CD4+ (day 30, p=0.012) and T-CD8+ lymphocytes (day 30, p=0.003). of immune profiles severe infection risk: Day 7: IgG< mg/dl + cells/uL (OR 3.327, p< 0.001, specificity 88.5%, PPV 72%); day 30: IgG<