Local IgE production and positive nasal provocation test in patients with persistent nonallergic rhinitis

BACKGROUND: Allergic rhinitis is an IgE-mediated inflammatory disease of the nasal mucosa, which is usually diagnosed by typical symptoms, positive skin tests, and/or serum specific IgE antibodies to allergens. Despite suggestive symptoms of allergic rhinitis, some patients have a negative diagnostic test for atopy. OBJECTIVE: To evaluate in the nose the inflammatory response, specific IgE to Dermatophagoides pteronyssinus (DP), and the response to a nasal allergen provocation test with DP (NAPT-DP), in patients with persistent nonallergic rhinitis (PNAR) compared with patients with persistent allergic rhinitis (PAR) and healthy controls. METHODS: Fifty patients with PNAR, 30 with PAR to DP, and 30 healthy controls were studied by determining the nasal leukocyte-lymphocyte phenotype by flow cytometry (CD16, CD8, CD4, CD33, CD3, and CD45), nasal eosinophil cationic protein (ECP), albumin, total and specific IgE to DP, and NAPT-DP. RESULTS: The PNAR patients showed a similar leukocyte-lymphocyte phenotype in nasal lavage to the PAR patients and was different to the healthy controls. Within the PNAR group, 54% showed a positive NAPT-DP, with 22% of these having nasal specific IgE to DP. CONCLUSION: These data support the hypothesis that in persistent nonallergic rhinitis some patients may have local inflammation, nasal IgE production, and a positive response to a nasal allergen provocation test despite no evidence of systemic atopy. Further research is needed to evaluate the influence of other perennial allergens and/or immunologic mechanisms. CLINICAL IMPLICATIONS: The local production of IgE antibodies without systemic detection is a condition that should be considered in patients with PNAR.     

Health-related quality of life in allergic rhinitis: comparing the short form ESPRINT-15 and MiniRQLQ questionnaires

BACKGROUND: We compared the psychometric properties of the ESPRINT-15, the short form of a new Spanish instrument to measure health-related quality of life in allergic rhinitis (AR) patients, with those of the Mini-Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ). METHODS: The questionnaires were compared in Spanish patients with intermittent allergic rhinitis (IAR) or persistent AR in a prospective, observational study. Floor and ceiling effects, internal consistency (Cronbach's alpha), test-retest reliability (intraclass correlation coefficient; ICC), convergent and known groups validity, and sensitivity to change (standardized response means; SRMs) were compared. RESULTS: In terms of content, while the MiniRQLQ has a dimension covering practical problems and places more emphasis on symptoms, the ESPRINT-15 has two dimensions (Sleep and Psychological impact) which are not included in the MiniRQLQ. In the validation study, 400 patients were included and 59% of the sample had persistent AR. There were no significant floor or ceiling effects on any dimension on either questionnaire. Cronbach's alpha values for the ESPRINT-15 and MiniRQLQ overall scores were 0.92 and 0.90, respectively. In 48 clinically stable patients, ICCs were 0.80 and 0.77, respectively. Both instruments discriminated between patients with IAR and persistent AR. Correlations with symptom scores and generic measures were moderate to strong. SRMs for overall scores and individual dimensions on the two questionnaires in the 197 patients reporting a change in health status ranged from 0.7 to 1.3. CONCLUSIONS: Both questionnaires performed well in psychometric terms. The ESPRINT-15 is particularly recommended for use in Spanish-speaking populations.     

Canine visceral leishmaniasis in northeast Brazil: epidemiological aspects

In a rural area of Northeast Brazil, the relatively high serological infection by Leishmania in dogs, the lack of classical vector Lutzomyia longipalpis and of American Visceral Leishmaniasis cases in human beings and the observation of Leishmania in ticks collected in infected dogs suggest that ticks may be responsible for the transmission between dogs.     

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.     

The Zung's autoscale for depression as predictor of sensorial and autonomic alterations to pain

Clinical and experimental evidence support a relationship between susceptibility to chronic pain and a subjacent depression. Nevertheless, it's not clear if the currently available clinical evaluation instruments for depression allow for linking both disorders. Thus, we evaluated a Zung's autoscale for depression and its different categories: affective, physiological, motor and psychological, as possible predictors of sensorial and autonomic alterations and vulnerability to clinical chronic pain. In 32 healthy controls and 11 subjects with minor depression and free of treatment, ischemic pain was first induced by applying a tourniquet on the dominant arm, and then followed by paresthesias during the reperfusion of arm as the tourniquet is released. Ischemic muscular pain, post-ischemic paresthesias and associated cardiovascular responses were recorded throughout the experimental procedure. The affective category's score was correlated linearly in individual form with the greatest number of variables and it was adjusted to a model of multiple regressions that almost explained the variance in 100% with a contribution of the sensorial and autonomic variables of a 70% and 30%, respectively. In addition, the affective category was 50% greater in subjects with persistent clinical pain. The Zung's index and the other categories had a smaller number of individual linear correlations and models of multiple correlations that only explained between 30-70% of the variance, with a more predominant contribution of the autonomic variables (20-50%), especially in the psychological category. This suggests that the affective category predicts cutaneous-muscular sensorial alterations with greater effectiveness than the Zung's total index.     

Adrenocortical function in patients with systemic mycoses

The systemic mycoses like paracoccidioidomycosis and histoplasmosis, are the main cause of adrenal insufficiency in the countries where they arc endemic. In Venezuela an elevated frequency of these mycoses has been registered. The objective of this study was to evaluate the glucocorticoid adrenal function in patients with paracoccidioidomycosis and histoplasmosis hospitalized in the University Hospital "Ruiz y Pácz" of Ciudad Bolivar (Bolivar state) and in the Hospital "Luis Felipe Rojas Guevara", of El Tigre (Anzoátegui state), Venezuela, between January 2003 and January 2004. The test of fast stimulation with synthetic adrenocorticotrophin hormone (ACTH) was applied to a total of 12 patients with diagnosis of some of these mycoses and data of epidemiologic interest were taken. The proportion men:women was of 5:1, the average age was 35.1 +/- 0.37 years, similar to the control group. Basal plasmatic cortisol levels were within the normal rank in all the patients. After the injection of synthetic ACTH, an increase of plasmatic cortisol values in the same rank for patients with a normal adrenal function was observed, but it was significantly lower than the observed for the control group. These results suggest that there is an adrenal gland functional reserve diminution in patients with either Paracoccidioidomycosis or Histoplasmosis. In patients with systemic mycoses, it is important to evaluate the response to the test of fast stimulation with ACTH due to the frequency of impairment of the glucocorticoid adrenal function in our location.     

Influence of KIR gene diversity on the course of HSV-1 infection: resistance to the disease is associated with the absence of KIR2DL2 and KIR2DS2

Herpes simplex virus type 1 (HSV-1) causes lifelong latent infections in most humans. Periodical virus reactivations from latency in the neurons of sensitive ganglia lead to transport to mucocutaneous regions and productive replication, which results in recurrent inflammatory herpetic lesions or in asymptomatic virus shedding. The medical consequences of such lesions and the frequency of recurrences vary greatly in different subjects. Furthermore, many infected individuals never suffer manifestations of the disease, even when exposed to stimuli that trigger clinical recurrences in other humans. The origin of the variability in the clinical course of HSV-1 infection remains unexplained. Herpesviruses and other pathogens sabotage the expression of major histocompatibility complex class I molecules by infected cells, thus subverting T-cell-mediated immunity. Subversion of antigen presentation is counteracted by natural killer cells, which survey the human leukocyte antigen (HLA) expression by specific receptors. These include the killer cell immunoglobulin-like receptors (KIRs), which are encoded by a complex of extremely diverse and rapidly evolving genes. Here, we analyze the contribution of KIR gene diversity to the variable clinical course of HSV-1 infection by comparing the distribution of these genes in humans with clinical manifestations of the disease with that in asymptomatically infected donors. This study provides preliminary evidence that the receptors KIR2DL2 and KIR2DS2 predispose to symptomatic HSV-1 infection and favor the frequently recurring forms of the disease. Possible contribution of the 'HLA-C1' ligand to HSV-1 disease was not statistically supported. Because of an absolute genetic linkage between KIR2DL2 and KIR2DS2, we could not determine which receptor was primarily responsible for the observed association, but our results suggest that presence in the genome of KIR2DL2 and KIR2DS2 hinders an effective cellular response to HSV-1.     

Fas ligand-dependent inflammatory regulation in acute myocarditis induced by Trypanosoma cruzi infection

Fas/Fas ligand (Fas-L) engagement, a potent inducer of apoptosis, is also important for cellular activation, regulation of effector and chemotactic activity, and secretion of chemokines and cytokines. We evaluated the relevance of Fas/Fas-L in the regulation of myocarditis induced by Trypanosoma cruzi infection and observed that in Fas-L(-/-) mice (gld/gld), cardiac infiltration was significantly reduced, accordingly showing less cardiomyocyte destruction. Fluorescence-activated cell sorting analysis of cardiac inflammatory cells showed higher numbers of CD8(+) T cells in BALB/c compared with gld/gld mice but similar levels of lymphocyte function-associated antigen-1, intercellular adhesion molecule, CD2, and CD69 expression; MAC-1(+) myeloid cells and mast cells were increased in BALB/c mice, whereas gld/gld mice exhibited an enrichment of CD4(+/low) T cells. Intracellular labeling of cytokines revealed no clear cardiac skewing of Th1 or Th2 responses, but we found a higher number of interleukin-10(+) cells in gld/gld mice and a deficient expression of vascular cell adhesion molecule-1 on cardiac endothelial cells in gld/gld mice. Finally, we found a population of CD3(+) but CD4/CD8 double negative cardiac T cells in both groups of infected mice, but down-regulation of some adhesion molecules and surface receptors was only observed in gld/gld mice, indicating a targeted T-cell population mostly affected by the lack of Fas-L engagement. These results point to a role for myocarditis regulation by Fas/Fas-L beyond its possible direct relevance in cellular death.     

Critical role for Ipaf in Pseudomonas aeruginosa-induced caspase-1 activation

Pseudomonas aeruginosa is an opportunistic Gram-negative human pathogen that is responsible for a broad range of infections in individuals with a variety of predisposing conditions. After infection, P. aeruginosa induces a marked inflammatory response in the host. However the mechanisms involved in bacterium recognition and induction of immune responses are poorly understood. Here we report that the Nod-like receptor family member Ipaf is required for optimal bacterial clearance in an in vivo model of P. aeruginosa lung infection. Further analysis showed that bacterial flagellin was essential for caspase-1 and IL-1beta and this activity depended on Ipaf and the adaptor ASC but not TLR5. Notably, P. aeruginosa induced macrophage cell death and this event relied on flagellin and Ipaf but not on ASC. Analysis of Pseudomonas mutants revealed that different amino acid residues of flagellin were critical for sensing by Ipaf and TLR5. Finally, activation of caspase-1 and IL-1beta secretion by P. aeruginosa required a functional type III secretion system, but not the effector molecules ExoS, ExoT and ExoY. These results provide new insight into the interaction of P. aeruginosa with host macrophages and suggest that distinct regions of flagellin are sensed by Ipaf and TLR5.