A new topical panthenol-containing emollient for maintenance treatment of childhood atopic dermatitis: results from a multicenter prospective study.

PURPOSE: A study was conducted with a new topical panthenol-containing emollient (NTP-CE) to investigate the efficacy and safety of a 3-month maintenance treatment in infants and children with stabilized mild atopic dermatitis (AD). METHODS: After the stabilization phase (up to 2 months) using a corticosteroid-free topical medical device, 108 subjects (aged 2-49 months) with a SCORing AD (SCORAD) on the target area of <5, were randomized to receive NTP-CE (N = 52) or reference emollient (N = 56) twice-daily for ∼3 months. SCORAD scores, occurrence of flares, and tolerability were assessed at regular intervals. RESULTS: In both groups, local SCORAD decreased during the study with a mean change from baseline (=end of stabilization phase) of -1.2 ± 1.3 (NTP-CE) and -1.0 ± 1.9. Kaplan-Meier analysis provided success rates (i.e. proportion of subjects without flares at study end) of 96 and 77% for the NTP-CE and reference group, respectively (p =.083, log-rank test). Mean time to flare-up was 47 days (range: 29-65) in the NTP CE group and 50 days (6-100). Study products were well tolerated. CONCLUSIONS: Our results indicate that NTP-CE is efficacious and safe when used for maintenance treatment of mild childhood AD.

Interchangeability of Quinvaxem during primary vaccination schedules: results from a phase IV, single-blind, randomized, controlled, single-center, non-inferiority study.

Combination vaccines against diphtheria, tetanus and pertussis (DTP) represent the core of childhood vaccination programs. Quinvaxem, a fully-liquid, pentavalent combination vaccine containing inactivated hepatitis B (HepB), Haemophilus influenzae type b (Hib) and whole-cell pertussis (wP) antigens, and tetanus and diphtheria toxoids, has been shown to be suitable for boosting children primed in infancy with another DTwP-HepB-Hib vaccine. This single-blind, randomized, controlled study was designed to demonstrate non-inferiority of a primary vaccination course (6-10-14 week schedule) of Tritanrix HB+Hib (first dose) and Quinvaxem (second/third doses) versus three doses of Quinvaxem with respect to the seroprotection/seroconversion rates for all antigens one month after vaccination course completion. Four hundred healthy subjects eligible for the local Expanded Program on Immunization were enrolled and equally randomized to the two treatment regimens. All subjects achieved seroprotection for tetanus and Hib, all except one for diphtheria, and all except two achieved seroconversion against Bordetella pertussis. Seroprotection against hepatitis B was achieved by 97.4% of Tritanrix HB+Hib followed by Quinvaxem and 94.9% of Quinvaxem subjects. Therefore, one month after vaccination course completion, seroprotection rates (seroconversion rate for B. pertussis) of Tritanrix HB+Hib followed by Quinvaxem were non-inferior to those elicited by Quinvaxem only, thus meeting the primary objective. Adverse events were comparable between the groups and were in line with the safety profile of the vaccines. The switch of vaccine had no apparent effect on safety endpoints. Our results support the use of Quinvaxem interchangeably with Tritanrix HB+Hib in a primary vaccination course and provides further evidence for the interchangeability of pentavalent vaccines (Clinical Trials.gov registry: NCT01357720).

Haploinsufficiency at the human IFNGR2 locus contributes to mycobacterial disease.

Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome, the known genetic etiologies of which impair the production of, or the response to interferon-gamma (IFN-γ). We report here a patient (P1) with MSMD whose cells display mildly impaired responses to IFN-γ, at levels, however, similar to those from MSMD patients with autosomal recessive (AR) partial IFN-γR2 or STAT1 deficiency. Whole-exome sequencing (WES) and Sanger sequencing revealed only one candidate variation for both MSMD-causing and IFN-γ-related genes. P1 carried a heterozygous frame-shift IFNGR2 mutation inherited from her father. We show that the mutant allele is intrinsically loss-of-function and not dominant-negative, suggesting haploinsufficiency at the IFNGR2 locus. We also show that Epstein-Barr virus transformed B lymphocyte cells from 10 heterozygous relatives of patients with AR complete IFN-γR2 deficiency respond poorly to IFN-γ, in some cases as poorly as the cells of P1. Naive CD4(+) T cells and memory IL-4-producing T cells from these individuals also responded poorly to IFN-γ, whereas monocytes and monocyte-derived macrophages (MDMs) did not. This is consistent with the lower levels of expression of IFN-γR2 in lymphoid than in myeloid cells. Overall, MSMD in this patient is probably due to autosomal dominant (AD) IFN-γR2 deficiency, resulting from haploinsufficiency, at least in lymphoid cells. The clinical penetrance of AD IFN-γR2 deficiency is incomplete, possibly due, at least partly, to the variability of cellular responses to IFN-γ in these individuals.

The expression of CD40 on monocytes of children with primary humoral immunodeficiencies.

The interactions between CD40 and CD40L (CD154) are critical for effective humoral immune response. CD40 signaling facilitates T lymphocyte dependent B cell proliferation and immunoglobulin isotype switch. The objective of our study was to investigate the CD40 and CD40L expression on peripheral blood mononuclear cells (PBMC) of children with symptomatic transient hypogammaglobulinemia (THI), common variable immunodeficiency (CVID) and selective IgA deficiency (SIgAD). Additionally we studied the production of IL-12 and IL-18 by PBMC stimulated with soluble CD40L. CD40 expression was analyzed on B cells and monocytes, CD40L on activated T lymphocytes, using flow cytometry following staining of the cells with appropriate MAb. We found that CD40 expression on B cells and CD40L on activated T cells were essentially similar in the control and patient groups, while the decreased CD40 expression on monocytes was observed in THI and SIgAD patients compared with normal subjects. The most significant decrease of CD40 expression was observed in THI (37% of positive cells) in comparison with control (81% of positive cells). IL-12, but not IL-18, release by PBMC was increased in THI and CVID, but not in SIgAD. In conclusion we suggest that the decreased expression of CD40 on monocytes of children with THI and SIgAD, but not CVID, may be involved in the pathomechanism of these immunodeficiencies.

Human immunodeficiency virus type 1 (HIV-1) antigen secretion by latently infected resting CD4+ T lymphocytes from HIV-1-infected individuals.

In resting CD4(+) T lymphocytes harboring human immunodeficiency virus type 1 (HIV-1), replication-competent virus persists in patients responding to highly active antiretroviral therapy (HAART). This small latent reservoir represents between 10(3) and 10(7) cells per patient. However, the efficiency of HIV-1 DNA-positive resting CD4(+) T cells in converting to HIV-1-antigen-secreting cells (HIV-1-Ag-SCs) after in vitro CD4(+)-T-cell polyclonal stimulation has not been satisfactorily evaluated. By using an HIV-1-antigen enzyme-linked immunospot assay, 8 HIV-1-Ag-SCs per 10(6) CD4(+) resting T cells were quantified in 25 patients with a plasma viral load of <20 copies/ml, whereas 379 were enumerated in 10 viremic patients. In parallel, 369 and 1,238 copies of HIV-1 DNA per 10(6) CD4(+) T cells were enumerated in the two groups of patients, respectively. Only a minority of latently HIV-1 DNA-infected CD4(+) T cells could be stimulated in vitro to become HIV-1-Ag-SCs, particularly in aviremic patients. The difference between the number of HIV-1 immunospots in viremic versus aviremic patients could be explained by HIV-1 unintegrated viral DNA that gave additional HIV-1-Ag-SCs after in vitro CD4(+)-T-cell polyclonal stimulation. The ELISPOT approach to targeting the HIV-1-Ag-SCs could be a useful method for identifying latently HIV-1-infected CD4(+) T cells carrying replication-competent HIV-1 in patients responding to HAART.

Involvement of pattern recognition receptors in the induction of cytokines and reactive oxygen intermediates production by human monocytes/macrophages stimulated with tumour cells.

BACKGROUND: Some ligands of pattern recognition receptors (PRR) are present on tumour cells. The role of PRR in signalling for cytokine and reactive oxygen intermediates (ROI) production by monocytes and monocyte-derived macrophages (MDM) stimulated with tumour cells was studied. MATERIALS AND METHODS: Monocytes/MDM were pretreated with PRR ligands or anti-PRR monoclonal antibodies (mAbs) and stimulated with tumour cells. Cytokine secretion was measured by enzyme-linked immunoassay (ELISA) and ROI production by luminol-dependent chemiluminescence (CL). RESULTS: The ligands of scavenger receptor A (SR-A): (fucoidan, polyguanylic acid (polyG) and modified low density lipoproteins (LDL)) and B (SR-B) (native and modified LDL, phosphatidylserine (PdS)) and of mannose receptor (MR) (mannan), induced tumour necrosis factor alpha (TNF) and ROI (except LDL) release by monocytes. Production of TNF and interleukin-10 (IL-10) by MDM was stimulated by SR-A ligands and mannan. Tumour cell-induced TNF and IL-10 production by monocytes, but not MDM, was diminished by fucoidan and polyG, while ROI release was reduced by MR and SR-A ligands. Supplementation of tumour cells with modified LDL and PdS enhanced their stimulatory capacity. TNF and ROI release by tumour cells-stimulated monocytes was inhibited by anti-CD36 and anti-MR (clone PAM-1) mAbs. CONCLUSION: SR and MR may be involved to different extents in the induction of cytokines and ROI production by monocytes, but not MDM, stimulated with tumour cells.

Detection and enumeration of circulating HIV-1-specific memory B cells in HIV-1-infected patients.

Memory B cells are long-living cells that circulate throughout the body and differentiate into plasma cells after stimulation by antigens, cytokines, and direct cell-to-cell interaction in lymphoid tissues. For HIV-1-infected patients, we assessed whether in vitro polyclonal B cell activation that induces immunoglobulin secreting cells (SCs) also generates HIV-1-specific resting B cells to synthesize antibodies specific to HIV-1. To this end, highly purified B cells from 10 HIV-1-untreated patients were cultured with or without mouse fibroblastic cells expressing the CD40 ligand in the presence of IL-2 and IL-10. The percentage of immunoglobulin SCs we obtained by using the B cell-CD40L stimulation system was equal to 55% to 98% of the circulating memory B cells. Moreover, the anti-HIV-1 IgG, IgA, or IgM antibody SCs represented 1 x 10-2 to 1 x 10-3 of the total immunoglobulin SCs. The anti-HIV-1-specific antibodies detected in cell culture supernatants were directed to gag-, pol-, and env-encoded viral proteins. We found that in AIDS patients, HIV-1-specific resting memory B cells circulate in the blood and can be quantified by their anti-HIV-1 antibody secretion after strong B cell polyclonal stimulation.

Extracellular matrix proteins modulate cytokine production by monocytes during their interactions with cancer cells.

BACKGROUND: This study examined the role of extracellular matrix compounds (EMC) in the alteration of tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) production by human monocytes stimulated with cancer cells. MATERIALS AND METHODS: Monocytes were cultured with cancer cells in the absence or presence of EMC and cytokine release was measured by ELISA. In some experiments monocytes preincubated with monoclonal antibodies (mAbs) against CD29 and CD44 were used. RESULTS: Fibronectin, collagen type I and type IV induced production of cytokines by monocytes and mAbs inhibited this effect. The release of TNF alpha monocytes stimulated with cancer cells was inhibited by fibronectin, collagen type I and IV and IL-10 by fibronectin and collagen type IV. Other EMC were ineffective. Both mAbs partly reversed this inhibitory effect. CONCLUSION: These findings suggest that some EMC induced cytokine release by monocytes but inhibit monocyte-cancer cell interactions and this effect is presumably due to competition for the same receptors.

Susceptibility to fungal infections of nails in patients with primary antibody deficiency.

Primary antibody deficiencies are rare diseases, which require early treatment with intravenous immunoglobulins to prevent fatal infections. The cell mediated immunity in patients with those immunodeficiencies remains unimpaired and usually they do not develop fungal infections. The aim of the study was to determine the susceptibility to fungal infections of nails in children with X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVID). Nail plate fragments collected from five patients with XLA and five with CVID were experimentally infected with a Candida albicans and Trichophyton mentagrophytes strains. The same procedures were carried out with the nails from a control group of 10 healthy volunteers. The intensity of the infection was evaluated on the basis of hyphae ingrown into the nail fragments. The main finding of the study was the increased susceptibility of antibody deficient patients to experimental nail infection with C. albicans and T. mentagrophytes.

[Immunologic methods in diagnosis of inflammatory bowel disease]. / Wspólczesne metody diagnostyki immunologicznej zapalnych schorzen jelit.

Chronic inflammatory bowel disease is included into autoimmune diseases, which is proved by presence of inflammatory lesions, circulating autoantibodies and the deposits of immune complexes in tissues. Coeliac disease (classic and atypical form), Crohn's Disease and ulcerative colitis are considered as chronic autoimmune bowel diseases. The auto-antibodies can be detected with indirect immunofluorescence, ELISA and immunoblotting methods. In coeliac disease the autoantibodies against endomysium (tissue transglutaminase) and antibodies against gliadin are found in patient's sera. The auto-antibody detecting is helpful in establishing diagnosis, controlling gluten-free diet effectiveness and during gluten challenge. In Crohn's disease and ulcerative colitis immunological laboratory tests are helpful to confirm the clinical diagnosis. The following auto-antibodies are tested: against cytoplasm of exocrinal pancreatic cells, and products of these cells, against the neutrophile cytoplasm and against goblet cells. The antibodies against Saccharomyces cerevisiae are also investigated. The clinical relevance of above autoantibodies is not clear, but it is suggested that their presence correlates with exacerbations and severe clinical outcome. In the present study the pictures of autoantibodies from fluorescent microscope were shown.

[Common variable immunodeficiency concomitant with liver cirrhosis--case report]. / Opis przypadku pospolitego zmiennego niedoboru odpornosci z towarzyszaca marskoscia watroby.

The authors present a report of a seventeen year old girl with common variable immunodeficiency (CVID) and liver cirrhosis. A child of healthy, non-consanguineous parents was diagnosed at the age of 13 years to have immune deficiency and an early stage of liver cirrhosis. Patient revealed the following signs of immune deficiency: decreased level of serum immunoglobulins, considerably decreased number of B cells and CD4 cells and a lack of proliferative response to mitogen stimulation. The USG, scintigraphy and biopsy of liver confirmed the diagnosis of liver cirrhosis. The patient has been receiving intravenous immunoglobulins (IVIG) as substitutional treatment of CVID.