Susanne Dam Nielsen

Reliable methods to assess immune function after solid organ transplantation (SOT) are needed to guide dosing of immunosuppression. We hypothesized that toll‐like receptor ligand‐induced cytokine concentrations would decrease post‐transplantation due to the use of immunosuppressive medication. Furthermore, we hypothesized that induced cytokine concentrations pre‐transplantation would be higher in recipients with episodes of acute rejection post‐transplantation due to underlying immunological dispositions. We aimed to investigate toll‐like receptor ligand‐induced cytokine concentrations by TruCulture©, a standardized immunoassay, in SOT recipients before and 3 months after SOT and explored associations with methylprednisolone‐treated acute rejections. We conducted a prospective, observational cohort study including 123 participants (67 liver, 32 kidney and 24 lung transplant recipients). Whole blood was stimulated for 22 h with: (A) Lipopolysaccharide (LPS), (B) Resiquimod, (C) Polyinosinic:polycytidylic acid (Poly I:C) and (D) a blank control. Cytokine concentrations (TNF‐α, IL‐1β, IL‐6, IL‐8, IL‐10, IL‐12p40, IL‐17A, IFN‐α and IFN‐γ) were measured by Luminex. 30 participants developed methylprednisolone‐treated acute rejection at a median of 9 days (IQR 5–17) post‐SOT. We found that all induced cytokine concentrations decreased post‐SOT except from LPS‐induced and Poly I:C‐induced IL‐10. The induced cytokine concentration pre‐transplantation did not differ in recipients with or without acute rejection. In conclusion, the induced cytokine concentrations decreased for all stimuli post‐SOT, except the anti‐inflammatory cytokine IL‐10. Importantly, recipients developing early acute rejection did not differ in induced cytokine concentrations pre‐SOT. Thus, the use of a standardized assay in SOT is feasible in a clinical setting and may provide important information on the immune function post‐SOT.

Background: People with HIV (PWH) have an increased risk of peripheral artery disease (PAD), but the pathogenesis is unknown. We aimed to determine the associations between markers of endothelial dysfunction and platelet activation and both PAD at baseline and de novo PAD in PWH. Methods: In total, 1012 PWH from the longitudinal Copenhagen Comorbidity in HIV-infection (COCOMO) study and 57 age-matched and sex-matched population controls were included. Plasma samples were collected at baseline and analyzed for soluble thrombomodulin, syndecan-1, and CD40 ligand (sCD40L). The ankle-brachial index was measured at baseline and two-year follow-up in PWH. Logistic and Poisson regression models were used to test associations. Results: PWH had higher concentrations of soluble thrombomodulin ( P = 0.03) and syndecan-1 ( P < 0.001) and lower concentration of sCD40L ( P < 0.001) compared with controls. High concentration of soluble thrombomodulin, but not syndecan-1 or sCD40L, was associated with lower odds of PAD in PWH at baseline after adjustments (adjusted odds ratio: 0.50 [0.28, 0.90], P = 0.02). None of the markers were associated with de novo PAD. Conclusions: PWH had higher concentrations of soluble thrombomodulin and syndecan-1 and lower concentration of sCD40L compared with controls. Soluble thrombomodulin was associated with lower odds of PAD at baseline. Further studies are needed to elucidate the pathogenesis of PAD in people with HIV.