Premature infants are at increased risk for persistent growth failure, neurodevelopmental impairment, hypertension, and diabetes. Rapid neonatal growth has been linked to the increasing prevalence of diabetes and obesity. Nutritional goals for the premature infant with incipient growth failure have thus become a source of controversy. We used isogenic mice with natural variation in perinatal growth to test the hypothesis that neonatal catch up growth improves the neurobehavioral and cardiovascular outcomes of lowbirth weight mice, despite an increase in diabetes susceptibility. Adult mice that experienced prenatal and neonatal growth restriction had persistent growth failure, hypertension, and neurobehavioral alterations. When switched from standard rodent chow to a hypercaloric diet, growth restricted mice were protected from diet-induced obesity. Among low-birth weight male mice, neonatal catch up growth normalized neurobehavioral and cardiovascular phenotypes, but led to insulin resistance and high fat diet-induced diabetes. Among low-birth weight female mice, neonatal catch up growth did not prevent the development of adult hypertension and significantly increased measures of anxiety, including self-injury and the avoidance of open spaces. These studies support the importance of the perinatal environment in the resetting of adult disease susceptibility and suggest an earlier window of vulnerability among growth restricted female mice. (Pediatr Res 66: 53-58, 2009) R estricted perinatal growth is an independent risk factor for the development of type 2 diabetes, hypertension, and coronary heart disease (1,2). The primary animal models of programmed adult disease induce fetal growth restriction through maternal nutrient restriction or uterine artery ligation (3). The development of diabetes and obesity in these models has been most dramatic when rodent pups are cross-fostered to well-nourished dams and then weaned to postnatal high-fat diets (4,5). These studies are consistent with epidemiologic data linking excessive weight gain in infancy with adult metabolic syndrome (6). Although these data suggest that restriction of neonatal nutrition might improve adult metabolic health, a comprehensive approach is essential when considering the long-term consequences of perinatal dietary alterations (7).Preterm delivery increases the risk of impaired growth during a critical window of brain development. By 36-wk postmenstrual age, ϳ90% of premature infants have growth failure (weight less than the 10th percentile of reference fetuses) (8). This perinatal growth failure is associated with permanent reductions in adult weight and height (9). It follows that premature delivery greatly increases the risk of neurodevelopmental impairment, insulin resistance, and adult hypertension (10 -12). As parallel epidemics of prematurity and obesity unfold, there is a critical need for research-based neonatal nutritional recommendations that seek to optimize short-term health and long-term outcomes.We previously evaluated th...

Several autoimmune diseases are marked by a deficiency of soluble tumor necrosis factor (TNF). The TNF deficiency is caused in at least one autoimmune disease, multiple sclerosis, by an overabundance of TNF receptor 1 (TNFR1). Excess TNFR1 binds and inactivates TNF and this leaves less TNF bioavailable. This study sought to determine if expression of fresh or IL2-stimulated TNF receptors on Tregs cells, an important immunoregulatory cell involved in autoimmunity, is altered in type I diabetes. Standard fluorescence analysis was used to examine the levels of TNFR1 and TNFR2 on human Tregs in patients with type I diabetes (T1D) or controls. Fresh Tregs from T1D compared to control Tregs had identical levels of TNFR1. In marked contrast, Type 1 diabetic patients Treg cells had statistically elevated levels of TNFR2 compared to controls. Tregs stimulated with IL2 from both T1D and controls showed marked increase of TNFR2 expression in a dose-response manner, but the dose response increase in TNFR2 was significantly higher for T1D Treg cells. No IL2 dose-response was present for TNFR1 on either T1D or control Tregs exposed to IL2. A large study of serum for secreted levels of TNFR2 also revealed elevated circulating levels consistent with the elevated surface expression on Tregs. These findings suggest that abnormal regulation of TNFR2 expression with elevated cellular and secreted levels of TNFR2 is a characteristic of Type 1 diabetes. It is possible that the relative deficiency of TNF in type I diabetes, in contrast to multiple sclerosis, is caused by excess expression of TNFR such as TNFR2, a binding structure for inactivating TNF. OPEN ACCESSAntibodies 2015, 4 35

Guillain-Barre syndrome (GBS) is an acute autoimmune demyelinating polyradiculoneuropathy that presents with rapidly progressive ascending muscle weakness. GBS typically follows a respiratory or gastrointestinal infection. Early detection and treatment can improve recovery rate [1]. We present a case of GBS induced by varicella zoster virus (VZV) reactivation in a patient receiving treatment for multiple myeloma. CASE PRESENTATION:A 68-year-old male with a history of multiple myeloma, abdominal aortic aneurysm with repair and hypertension initially presented to the emergency department (ED) with fever and altered mental status. In the ED, his blood pressure was initially 210/134 and remained elevated despite intravenous (IV) administration of labetalol. The patient was started on empiric therapy with IV vancomycin, acyclovir, ceftriaxone, and ampicillin for possible meningitis. It was found that the patient had previously received an autologous stem cell transplantation, as well as treatment with bortezomib, lenalidomide, and low-dose dexamethasone, with only partial response. The patient was started on an escalated regimen with daratumumab one week prior to admission. The patient was transferred to the intensive care unit (ICU) and placed on an IV esmolol drip for hypertensive emergency. The next day, the patient developed bilateral lower extremity areflexia and motor weakness. IV immunoglobulin (IVIg) was initiated for presumed GBS. Cerebrospinal fluid (CSF) results were significant for positive VZV-PCR and elevated protein. Magnetic resonance imaging (MRI) of the brain showed a linear enhancement in the cauda equina that was consistent with GBS. The patient continued to receive acyclovir and IVIg with clinical improvement.DISCUSSION: GBS induced by reactivation of latent VZV is rare. Prompt initiation of empiric treatment is imperative to prevent further complications and decrease time to recovery. Patients may also present with labile blood pressures or arrhythmias due to dysautonomia and should be monitored closely for cardiovascular and respiratory stability. Daratumumab is an IgG1 subtype human monoclonal antibody directed against CD38, a cell surface glycoprotein that is highly expressed in myeloma cells. Previous studies have noted infection complications of daratumumab [2-5], including reactivation of a viral infection. Further studies investigating the role of prophylaxis and screening in individuals who begin immunomodulatory therapies should be considered. CONCLUSIONS:In an immunocompromised patient presenting with bilateral lower extremity areflexia and motor weakness, GBS should be considered with prompt initiation of appropriate therapy. This case report highlights the importance of a thorough history, prompt treatment, and close follow-up to avoid adverse outcomes.

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