Angiotensin II Type-1 Receptor Antibodies Are Associated With Active Allograft Dysfunction Following Pediatric Liver Transplantation
Authors: Wozniak, Laura J.; Hickey, Michelle J.; Chan, Alvin P.; Venick, Robert S.; Farmer, Douglas G.; Busuttil, Ronald W.; Reed, Elaine F.; McDiarmid, Sue V.
Background. Angiotensin II type-1 receptor (AT1R) antibodies have been associated with rejection and allograft loss in solid organ transplantation and may act synergistically with HLA donor-specific antibodies (DSA). Our aims were to assess the prevalence of AT1R antibodies and determine if they were associated with allograft dysfunction in pediatric liver transplant recipients. Methods. We performed a retrospective, cross-sectional study of HLA DSA and AT1R antibodies in 2 cohorts of pediatric liver transplant recipients: a stable control cohort with normal allograft function (n = 70) who consented to have serum samples collected for research purposes during a routine clinic visit and a cohort with active allograft dysfunction (n = 9) whose serum samples were collected as part of clinical care. Results. AT1R antibodies >17 U/mL were detected in 29% of stable control patients and 89% of patients with active allograft dysfunction (P = 0.001). In stable control patients, AT1R antibodies were associated with younger age at transplant (P = 0.010), younger age at time of sample collection (P < 0.001), shorter interval since transplant (P = 0.090), and presence of HLA DSA (P = 0.003). AT1R antibodies in stable control patients were not associated with rejection or allograft loss. However, AT1R antibodies combined with HLA DSA in patients with active allograft dysfunction were associated with rejection and allograft loss. Conclusions. Our results suggest that AT1R antibodies are more common in patients with active allograft dysfunction and may be a risk factor for worse outcomes. Further research is needed to longitudinally assess the clinical impact of HLA DSA and AT1R antibodies.
Serum folate and cytokines in heterozygous beta-thalassemia
INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY
Authors: Paniz, Clovis; Lucena, Maylla Rodrigues; Bertinato, Juliano Felix; dos Santos, Magnun Nueldo Nunes; Gomes, Guilherme Wataru; Figueiredo, Maria Stella; Sonati, Maria de Fatima; Blaia-D Avila, Vera Lucia Nascimento; Green, Ralph; Guerra-Shinohara, Elvira Maria
Introduction Folate deficiency is commonly reported in beta-thalassemia. Individuals heterozygous for beta-thalassemia may have higher folate requirements than normal individuals. Objectives: To document the concentration of serum total folate and its forms in beta-thalassemia heterozygote users (beta-TmU) and nonusers (beta-TmN) of 5 mg folic acid/d; to determine whether folic acid (FA) consumption from fortified foods allows beta-Tm patients, who do not take FA supplements, to meet their dietary folate requirements; and to investigate the association between higher serum unmetabolized folic acid (UMFA) and inflammatory cytokine concentrations. Methods Serum total folate and forms were measured in 42 beta-Tm (13 beta-TmU and 29 beta-TmN) and 84 healthy controls. The mononuclear leucocyte mRNA expression of relevant genes and their products and hematological profiles were determined. Results beta-TmU had higher serum total folate, 5-methyltetrahydrofolate, UMFA, and tetrahydrofolate (THF) compared with beta-TmN. The beta-TmN had lower serum total folate and THF than controls. Plasma total homocysteine (tHcy) was lower in beta-TmU compared with both beta-TmN and controls, while beta-TmN had higher tHcy than controls. beta-TmU had higher IL-8 than their controls while beta-TmN had higher IL-6 and IL-8 than their controls. beta-TmU have higher levels of serum total folate, 5- methyltetrahydrofolate, UMFA, and THF than controls. There was no association between UMFA concentrations and cytokine levels. Conclusions Mandatory flour fortification with FA in Brazil may be insufficient for beta-TmN, since they have higher tHcy and lower serum total folate than controls. Furthermore, beta-TmN have higher IL-6 levels than beta-TmU. UMFA was not associated with inflammatory cytokine levels.