IL-27 posttranslationally regulates Y-box binding protein-1 to inhibit HIV-1 replication in human CD4+ T cells.

Objectives: IL-27 is known as an antiviral cytokine that inhibits HIV, hepatitis C virus, and other viruses. We have previously demonstrated that, IL-27 posttreatment after HIV-infection inhibits viral replication in primary CD4 T cells.

Design: Here, we evaluated the anti-HIV effect of IL-27 pretreatment in CD4 T cells from healthy donors prior to HIV infection with HIVNL4.

Hydroa vacciniforme-like lymphoproliferative disorder: an EBV disease with a low risk of systemic illness in whites.

Patients with classic hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) typically have high levels of Epstein-Barr virus (EBV) DNA in T cells and/or natural killer (NK) cells in blood and skin lesions induced by sun exposure that are infiltrated with EBV-infected lymphocytes. HVLPD is very rare in the United States and Europe but more common in Asia and South America. The disease can progress to a systemic form that may result in fatal lymphoma.

A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection.

Background: Herpes simplex virus 2 (HSV2) causes genital herpes in >400 million persons worldwide.

Methods: We conducted a randomized, double-blinded, placebo-controlled trial of a replication-defective HSV2 vaccine, HSV529. Twenty adults were enrolled in each of 3 serogroups of individuals: those negative for both HSV1 and HSV2 (HSV1-/HSV2-), those positive or negative for HSV1 and positive for HSV2 (HSV1±/HSV2+), and those positive for HSV1 and negative for HSV2 (HSV1+/HSV2-).

Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling.

Background: The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days after infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection.

Methods: Gene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls.

HLA-DQ 1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells.

Epstein-Barr virus (EBV) infects B cells and ~95% of adults are infected. EBV glycoprotein gp42 is essential for entry of virus into B cells. EBV gp42 binds to the β1 chain of HLA-DQ, -DR, and -DP on B cells, and uses these molecules for infection.

Elevated interleukin-10: a new cause of dyslipidemia leading to severe HDL deficiency.

Background: Low high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. Investigating mechanisms underlying acquired severe HDL deficiency in noncritically ill patients ("disappearing HDL syndrome") could provide new insights into HDL metabolism.

Objective: To determine the cause of low HDL-C in patients with severe acquired HDL deficiency.

Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations.

Autoimmune lymphoproliferative syndrome (ALPS) presents in childhood with nonmalignant lymphadenopathy and splenomegaly associated with a characteristic expansion of mature CD4 and CD8 negative or double negative T-cell receptor αβ(+) T lymphocytes. Patients often present with chronic multilineage cytopenias due to autoimmune peripheral destruction and/or splenic sequestration of blood cells and have an increased risk of B-cell lymphoma. Deleterious heterozygous mutations in the FAS gene are the most common cause of this condition, which is termed ALPS-FAS.

Interleukin-27 is a potent inhibitor of cis HIV-1 replication in monocyte-derived dendritic cells via a type I interferon-independent pathway.

IL-27, a member of the IL-12 family of cytokines, plays an important and diverse role in the function of the immune system. Whilst generally recognized as an anti-inflammatory cytokine, in addition IL-27 has been found to have broad anti-viral effects. Recently, IL-27 has been shown to be a potent inhibitor of HIV-1 infection in CD4+ T cells and macrophages.

IL-27 inhibits HIV-1 infection in human macrophages by down-regulating host factor SPTBN1 during monocyte to macrophage differentiation.

The susceptibility of macrophages to HIV-1 infection is modulated during monocyte differentiation. IL-27 is an anti-HIV cytokine that also modulates monocyte activation. In this study, we present new evidence that IL-27 promotes monocyte differentiation into macrophages that are nonpermissive for HIV-1 infection.

Partial immune reconstitution of X-linked hyper IgM syndrome with recombinant CD40 ligand.

X-linked hyper IgM syndrome (XHM) is a combined immune deficiency disorder caused by genetic alterations in CD40 ligand. The purpose of this study was to investigate the safety and efficacy of recombinant CD40 ligand (rCD40L) in the treatment of the disease. Three children were administered rCD40L subcutaneously 3 times per week at 0.

Dendritic cells from humans with hypomorphic mutations in IKBKG/NEMO have impaired mitogen-activated protein kinase activity.

The covalent attachment of lysine 63-linked polyubiquitin to the zinc-finger domain of IKBKG/NEMO (also known as IKKγ) is necessary for full activation of NF-κB. Impairments of this biochemical mechanism explain the deleterious effects of hypomorphic NEMO mutations on NF-κB signaling function in humans suffering from X-linked ectodermal dysplasia and immunodeficiency. Nevertheless, the biological function of the NEMO zinc-finger domain in the regulation of mitogen-activated protein kinase (MAPK) activity is poorly understood.

Suppression of inflammation in ulcerative colitis by interferon-β-1a is accompanied by inhibition of IL-13 production.

Objective: Ulcerative colitis is associated with increased interleukin 13 (IL-13) production by natural killer T cells. Taking advantage of the inhibitory actions of interferon β on IL-13 expression, this proof-of-concept study aimed to show that decreasing IL-13 production is associated with clinical improvement of ulcerative colitis symptoms.

Design: Open-label interventional drug trial.

Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome.

Autoimmune lymphoproliferative syndrome (ALPS) is characterized by childhood onset of lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias, elevated numbers of double-negative T (DNT) cells, and increased risk of lymphoma. Most cases of ALPS are associated with germline mutations of the FAS gene (type Ia), whereas some cases have been noted to have a somatic mutation of FAS primarily in their DNT cells. We sought to determine the proportion of patients with somatic FAS mutations among a group of our ALPS patients with no detectable germline mutation and to further characterize them.

Kinetics of serum cytokines after primary or repeat vaccination with the smallpox vaccine.

Background: The smallpox vaccine is associated with more serious adverse events than any other live attenuated vaccine in use today. Although studies have examined serum cytokine levels in primary vaccine recipients at 1 and 3-5 weeks after vaccination with the smallpox vaccine, serial measurements have not been performed, and studies in revaccinated subjects have not been conducted.

Methods: We analyzed cytokine responses in both primary vaccine recipients and revaccinated subjects every other day for 2 weeks after vaccination.

Serological diagnosis of human herpes simplex virus type 1 and 2 infections by luciferase immunoprecipitation system assay.

Highly quantitative and high-throughput serological tests for evaluation of humoral responses to herpes simplex virus 1 (HSV-1) and HSV-2 are not available. The efficacy of luciferase immunoprecipitation system (LIPS) assays for antibody profiling and serologic diagnosis of HSV-1 and HSV-2 infection was investigated using a panel of five recombinant HSV antigens. Plasma samples from subjects seropositive for HSV-1 and/or HSV-2 or seronegative for HSV-1 and HSV-2 that had previously been analyzed by Western blotting and the Focus Plexus immunoassay were evaluated.

Relapsing fever borreliosis in interleukin-10-deficient mice.

Relapsing fever (RF) is a spirochetal infection characterized by periods of sickness with fever at time of high bacteremia that alternate with afebrile periods of relative well being during low bacteremia. Patients with epidemic RF who are doing relatively well have extraordinarily high levels of interleukin-10 (IL-10) in the circulation. We investigated the possibility that IL-10 plays an important protective role in this infection using wild-type and IL-10-deficient mice inoculated with virulent serotype 2 of the RF spirochete Borrelia turicatae.

IL-10 helps control pathogen load during high-level bacteremia.

During relapsing fever borreliosis, a high pathogen load in the blood occurs at times of peak bacteremia. Specific IgM Abs are responsible for spirochetal clearance so in absence of B cells there is persistent high-level bacteremia. Previously, we showed that B cell-deficient mice persistently infected with Borrelia turicatae produce high levels of IL-10 and that exogenous IL-10 reduces bacteremia.

Borrelia burgdorferi lipoprotein-mediated TLR2 stimulation causes the down-regulation of TLR5 in human monocytes.

Toll-like receptors (TLRs) trigger innate immune responses via the recognition of conserved pathogen-associated molecular patterns. Lipoproteins from Borrelia burgdorferi, the agent of Lyme disease, activate inflammatory cells through TLR2 and TLR1. We show that stimulation of human monocytes with B.

Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody.

Background: Interleukin (IL)-12p70 and IL-23 are key T helper-1 (TH1) cytokines that drive the inflammation seen in numerous models of intestinal inflammation. These molecules contain an identical p40 chain that is bound to a p35 chain in IL-12 and a p19 chain in IL-23, making both potentially susceptible to modulation by an anti-IL-12p40 monoclonal antibody (mAb).

Methods: In the present study, we sought to determine whether active inflammation in Crohn's disease (CD) is associated with the increased synthesis of both of these cytokines and whether patients treated with an anti-IL-12p40 mAb down-regulate IL-23 as well as IL-12p70 as previous reported.

Detection of immune complexes is not independent of detection of antibodies in Lyme disease patients and does not confirm active infection with Borrelia burgdorferi.

The Borrelia burgdorferi-specific immune complex (IC) test, which uses polyethylene glycol (PEG) precipitation to isolate ICs from serum, has been used as a research test in the laboratory diagnosis of early Lyme disease (LD) and has been proposed as a marker of active infection. We examined whether B. burgdorferi-specific antibodies were present within PEG-precipitated ICs (PEG-ICs) in patients with LD, posttreatment Lyme disease syndrome, and controls, including individuals who received the outer surface protein A (OspA) vaccine.

Anti-interleukin-12 antibody for active Crohn's disease.

Background: Crohn's disease is associated with excess cytokine activity mediated by type 1 helper T (Th1) cells. Interleukin-12 is a key cytokine that initiates Th1-mediated inflammatory responses.

Methods: This double-blind trial evaluated the safety and efficacy of a human monoclonal antibody against interleukin-12 (anti-interleukin-12) in 79 patients with active Crohn's disease.