Macrophage Migration Inhibitory Factor (MIF) Prevents Maternal Death, but Contributes to Poor Fetal Outcome During Congenital Toxoplasmosis.

Migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays important roles in physiology, pathology, immunology and parasitology, including the control of infection by protozoa parasites such as Toxoplasma gondii. As the MIF function in congenital toxoplasmosis is not fully elucidated yet, the present study brings new insights for T. gondii infection in the absence of MIF based on pregnant C57BL/6MIF-/- mouse models. Pregnant C57BL/6MIF-/- and C57BL/6WT mice were infected with 05 cysts of T. gondii (ME49 strain) on the first day of pregnancy (dop) and were euthanized at 8 dop. Non-pregnant and non-infected females were used as control. Our results demonstrated that MIF-/- mice have more accentuated change in body weight and succumbed to infection first than their WT counterparts. Otherwise, pregnancy outcome was less destructive in MIF-/- mice compared to WT ones, and the former had an increase in the mast cell recruitment and IDO expression and consequently presented less inflammatory cytokine production. Also, MIF receptor (CD74) was upregulated in MIF-/- mice, indicating that a compensatory mechanism may be required in this model of study. The global absence of MIF was associated with attenuation of pathology in congenital toxoplasmosis, but resulted in female death probably because of uncontrolled infection. Altogether, ours results demonstrated that part of the immune response that protects a pregnant female from T. gondii infection, favors fetal damage.

Modulation of mucosal/systemic antibody response after sublingual immunotherapy in mite-allergic children.

BACKGROUND: There have been no data on sublingual immunotherapy (SLIT) in Brazilian patients sensitized to house dust mites. This study aimed to evaluate the mucosal/systemic antibody response changes and clinical efficacy after SLIT using Dermatophagoides pteronyssinus (Dpt) allergens with or without bacterial extracts in mite-allergic Brazilian children. METHODS: Patients with allergic rhinitis and asthma were selected for a double-blind, placebo-controlled trial randomized to three groups: DPT (Dpt extract, n = 34), DPT+MRB (Dpt plus mixed respiratory bacterial extracts, n = 36), and Placebo (n = 32). Total symptom and medication scores for rhinitis/asthma, skin prick test (SPT) to Dpt, and measurements of Dpt-, Der p 1-, Der p 2-specific serum IgE, IgG4, IgG1, and specific salivary IgA were evaluated at baseline and after 12 and 18 months of treatment. RESULTS: A significant long-term decline in total symptom/medication scores was observed only in active groups (DTP and DPT+MRB). There was no significant change in SPT results in all groups. SLIT using Dpt allergen alone induced increased levels of serum IgG4 to Dpt, Der p 1, and Der p 2, serum IgG1 and salivary IgA to Dpt and Der p 1. SLIT with Dpt plus bacterial extracts was able to decrease IgE levels, particularly to Der p 2, to increase salivary IgA levels to Der p 1, but had no changes on specific IgG4 and IgG1 levels. CONCLUSIONS: All children undergoing SLIT showed clinical improvement, but a long-term reduction in symptom/medication scores with modulation of mucosal/systemic antibody responses were seen only in active groups (DPT and DPT+MRB).

Immunoproteomics of Brucella abortus reveals differential antibody profiles between S19-vaccinated and naturally infected cattle.

Brucella abortus is a Gram-negative intracellular bacterium that causes infectious abortion in food-producing animals and chronic infection in humans. This study aimed to characterize a B. abortus S19 antigen preparation obtained by Triton X-114 (TX-114) extraction through immunoproteomics to differentiate infected from vaccinated cattle. Three groups of bovine sera were studied: GI, 30 naturally infected cows; GII, 30 S19-vaccinated heifers; and GIII, 30 nonvaccinated seronegative cows. One-dimensional (1D) and two-dimensional electrophoretic profiles of TX-114 hydrophilic phase antigen revealed a broad spectrum of polypeptides (10-79 kDa). 1D immunoblot showed widespread seroreactivity profile in GI compared with restricted profile in GII. Three antigenic components (10, 12, 17 kDa) were recognized exclusively by GI sera, representing potential markers of infection and excluding vaccinal response. The proteomic characterization revealed 56 protein spots, 27 of which were antigenic spots showing differential seroreactivity profile between GI and GII, especially polypeptides <20 kDa that were recognized exclusively by GI. MS/MS analysis identified five B. abortus S19 proteins (Invasion protein B, Sod, Dps, Ndk, and Bfr), which were related with antigenicity in naturally infected cattle. In conclusion, immunoproteomics of this new antigen preparation enabled the characterization of proteins that could be used as tools to develop sensitive and specific immunoassays for serodiagnosis of bovine brucellosis, with emphasis on differentiation between S19 vaccinated and infected cattle.

Eficácia clínica da imunoterapia nasal comparada com imunoterapia sublingual em pacientes com rinite alérgica / Clinical efficacy of nasal immunotherapy compared to sublingual immunotherapy in patients with allergic rhinitis

A eficácia da imunoterapia (IT) com extratos alergênicos em pacientes com rinite alérgica (RA) tem sido demonstrada por via subcutânea ou sublingual, não existindo comprovação da eficácia terapêutica da IT tópica nasal. Objetivo: Comparar a eficácia da IT sublingual com a IT tó¬pica nasal em pacientes com RA. Pacientes e Método: Quarenta indivíduos com RA persistente, leve ou moderada, foram divididos em dois grupos em estudo prospectivo, duplo-cego, randomizado, com duração de doze meses. O grupo I utilizou IT tópica nasal com extratos alergênicos de ácaros da poeira domiciliar + placebo sublingual e o grupo II foi submetido a IT sublingual com extratos alergênicos + placebo tópico nasal. Foram realizadas oito avaliações durante o estudo, determinando-se a gravidade da RA e o consumo de medicamentos, além das alterações das mucosas nasais ao exame físico. Níveis de IgE e IgG4 anti-Oermatophagoides pteronyssinus foram determinados em amostras de soro de 22 pacientes, antes e após tratamento. Resultados: Vinte e cinco pacientes concluíram o estudo (grupo I, n=l1 e grupo lI, n=14). Redução significante na gravidade da RA e no consumo de medicamentos foi observada após tratamento nos dois grupos, enquanto que a redução nas alterações da mucosa nasal só foi observada no grupo Il. Não se observaram alterações significantes nos níveis de IgE e IgG4 anti-D. pteronyssinus nos dois grupos. Conclusão: Ambos os procedimentos de IT (sublingual e nasal) são eficazes na redução dos sintomas e do consumo de medicamentos de pacientes com RA por alérgenos de ácaros da poeira domiciliar. No grupo de pacientes que receberam IT sublingual, houve redução nas alterações da mucosa nasal.

Several studies have demonstrated the efficacy of subcutaneous or sublingual immunotherapy (IT) with allergen extracts for the treatment of perennial allergic rhinitis (AR), but there are no actual data on nasal IT efficacy. Aim: Evaluate the efficacy of topical nasal IT compared to sublingual IT in AR patients. Patients and Methods: Forty patients with mild or mederate perennial AR were selected to participate on this prospective, one-year follow-up, doubleblind randomized study. They were divided in 2 groups: group I (n=20) was treated with sublingual IT containing mite allergen extracts plus placebo on nasal mucosa and group II (n=20) was treated with topical nasal IT containing mite allergen extracts plus placebo via sublingual. A total of eight evaluations were performed during the follow-up to determine rhinitis severity and medicine consumption, as well as abnormalities of nasal mucosa. IgE and IgG4 antibodies anti-Oermatophagoides pteronyssinus were determined in serum samples of 22 subjects before and after IT. Results: Twenty-five subjects concluded the study (group I, n=l1 and group lI, n=14). There was a significant reduction on rhinitis severity and medicine consumption before and after the treatment in both groups. In addition there was a significant reduction on nasal mucosa abnormalities before and after treatment in group II patients. There were no changes on leveis of IgE or IgG4 antibodies anti-D. pteronyssinus before and after IT in both groups. Conclusion: The efficacy of sublingual and nasal IT was demonstrated in patients with AR, by reducing symptoms and medicine consumption. In addition, sublingual IT also reduced nasal mucosa abnormalities.

Heterogeneidade da resposta de anticorpos IgE aos alérgenos principais de Dermatophagoides pteronyssinus entre pacientes com alergia respiratória: Implicações para a imunoterapia específica com alérgenos / Heterogeneity of the IgE antibody response to major allergens from Dermatophagoides pteronyssinus among patients with respiratory allergy: Implications for allergen-specific immunotherapy

Objetivo: Analisar os níveis de IgE sérica específica aos alérgenos Der p 1 e Der p 2 de Dermatophagoides pteronyssinus (Dpt) em pacientes com alergia respiratória e comparar com as sensibilizações in vivo (teste cutâneo de puntura - TCP) e in vitro (ELISA- IgE) ao extrato total de Dpt. Métodos: Um total de 73 pacientes atópicos apresentando rinite alérgica com ou sem asma moderada e TCP positivo ao extrato total de Dpt foram estudados. Trinta indivíduos saudáveis com TCP negativo a ácaros da poeira domiciliar foram incluídos como controles. Níveis de IgE total e IgE específica a Dpt, Der p 1 e Der p 2 foram determinados por ELISA em pacientes atópicos (TCP+) e indivíduos controles não atópicos (TCP-). Resultados: Dos 73 pacientes atópicos, 38 (52 por cento) foram IgE duplo positivos aos alérgenos Der p 1 e Der p 2 (Der p 1+/Der p 2+), 11 (15 por cento) foram IgE positivos somente para Der p 1 (Der p 1+/Der p 2–), 7 (10po9r cento) foram IgE positivos somente para Der p 2 (Der p 1–/Der p 2+) e 17 (23 por cento) foram IgE duplo negativos para ambos alérgenos (Der p 1–/Der p 2–). Correlações significativas foram encontradas entre os níveis de IgE anti-Dpt e seus alérgenos (Der p1 ou Der p 2) bem como entre IgE anti-Der p 1 e anti-Der p 2 (P < 0,0001), mas não entre IgE específica a Dpt, Der p 1 ou Der p 2 e resultados do TCP. Pacientes com IgE duplo negativos apresentaram níveis de IgE anti-Dpt (IE = 1,4 ± 0,9) significativamente menores que os outros grupos, embora com altos níveis médios de IgE sérica total e valores de TCP. Conclusões: Os pacientes com alergia respiratória que apresentaram TCP+ ao extrato Dpt mostraram grande heterogeneidade da resposta de anticorpos IgE aos alérgenos principais de D. pteronyssinus, particularmente Der p 1 e Der p 2 e portanto, a determinação desses anticorpos específicos pode ser de grande valia para indicação e/ou seguimento de pacientes sensibilizados a ácaros sob imunoterapia específica com alérgenos.