A TNF-p100 pathway subverts noncanonical NF-κB signaling in inflamed secondary lymphoid organs.

Lymphotoxin-beta receptor (LTßR) present on stromal cells engages the noncanonical NF-κB pathway to mediate RelB-dependent expressions of homeostatic chemokines, which direct steady-state ingress of naïve lymphocytes to secondary lymphoid organs (SLOs). In this pathway, NIK promotes partial proteolysis of p100 into p52 that induces nuclear translocation of the RelB NF-κB heterodimers. Microbial infections often deplete homeostatic chemokines; it is thought that infection-inflicted destruction of stromal cells results in the downregulation of these chemokines. Whether inflammation per se also regulates these processes remains unclear. We show that TNF accumulated upon non-infectious immunization of mice similarly downregulates the expressions of these chemokines and consequently diminishes the ingress of naïve lymphocytes in inflamed SLOs. Mechanistically, TNF inactivated NIK in LTßR-stimulated cells and induced the synthesis of Nfkb2 mRNA encoding p100; these together potently accumulated unprocessed p100, which attenuated the RelB activity as inhibitory IκBδ. Finally, a lack of p100 alleviated these TNF-mediated inhibitions in inflamed SLOs of immunized Nfkb2-/- mice. In sum, we reveal that an inhibitory TNF-p100 pathway modulates the adaptive compartment during immune responses.

El sistema inmune en los linfedemas y linfangitis de los miembros inferiores / The immune system in lymphedema and lymphangitis of the lower limbs

El sistema inmune es el mecanismo de resistencia del organismo ante las infecciones. El sistema linfático juega un importante papel en el control fisiológico del fluido tisular y en la iniciación de la respuesta inmune. Nos proponemos describir la función de los componentes celulares del sistema inmune en las linfopatías de miembros inferiores no asociadas a cánceres tales como el linfedema y la linfangitis.Se revisaron las bases de datos PubMed, MedLine, SciELO, Clinical Key, Liliacs, Ebsco y artículos científicos publicados en revistas cubanas entre 2000-2015. Los estudios recientes muestran que el crecimiento de nuevos vasos linfáticos es una característica distintiva de las reacciones inflamatorias agudas y crónicas que caracterizan a las linfopatías, mediado por un incremento en el drenaje del fluido fuera del vaso y de células inflamatorias, así como de la modulación de las respuestas inmunes. Es apremiante continuar investigando, específicamente en lo concerniente al comportamiento de la inmunidad humoral y celular en los pacientes que padecen de linfedema o linfangitis, pues no se encontraron trabajos que aborden de manera específica la posible relación entre ambos. Se sugiere que las subpoblaciones de células T son un componente crítico en la respuesta celular inflamatoria crónica y subaguda en las linfopatías. La comprensión de la función reguladora del fluido linfático en la respuesta inflamatoria puede dar un importante paso en el desarrollo de tratamientos que puedan bloquear el inicio o la progresión de las consecuencias anómalas de las lesiones linfáticas(AU)

The immune system is the body´s mechanism of resistance to infections. The lymph system plays an important role in the physiological control of the tissue fluid and in the onset of the immune response. We intended to describe the function of the cell components of the immune system in the cancer-unrelated lymphopathies of the lower limbs such as lymphedema and lymphangitis. To this end, Pubmed, Medline, Scielo, Clinical Key, Liliacs, Ebsco and scientific articles published in Cuban medical journals from 2000 to 2015 were reviewed. The recent studies show that the growth of new lymphatic vessels is a distinctive characteristic of the acute and chronic inflammatory reactions of lymphopathies, mediated by increase of the fluid drainage outside the vessel and of inflammatory cells as well as the immune response modulations. It is urgent to continue studying this topic, mainly the behavior of the humoral and cell immunity in patients suffering from lymphedema or lymphangitis, since no research papers dealing with the possible relation between both aspects were found. It is suggested that the T-cell subpopulations are a key component of the chronic and sub-acute inflammatory response in lymphopaties. Hence, understanding of the regulating function of the lymph fluid in the inflammatory response may represent an important step in the development of therapies that might block the onset or progression of the anomalous consequences of lymphatic injures(AU)

The relationship between coronal sulcus lymphangitis and IgE / Relación entre la linfangitis del surco coronario y la IgE

Objectives. To investigate whether there is a link between serum IgE levels in patients having diagnosis of coronal sulcus lymphangitis and this disease. The patients and method. The patients have been diagnosed clinically. The time of symptoms’ existence, allergy history and the history of a traumatic sexual relationship or masturbation have been investigated. The serum total IgE levels have been measured. Results. The study includes 27 patients. All patients have been diagnosed clinically. The age average is 36 (22-54). The time between the last sexual relationship or masturbation and the emergence of the symptoms is averagely 3 days (1-10). The symptoms emerged in shorter than 24 h in 6 patients. The symptoms emerged statistically earlier in patients having a traumatic sexual relationship or masturbation history (p: 0.0046). The level of serum IgE was over the threshold value in 8 patients (30%). The symptoms emerged statistically later in patients having high IgE level (p: 0.0004). Conclusions. The immunologic, traumatic and infectious reasons are responsible for the etiology of the coronal sulcus lymphangitis. In this study, the rate of the patients considered to be having immunologic reasons has been found as 30% (AU)

Objetivo. Investigar si existe una relación entre los niveles séricos de IgE en pacientes diagnosticados de linfangitis del surco coronario y este resultado. Pacientes y métodos. Los pacientes recibieron un diagnóstico clínico. Se investigaron la duración de los síntomas, antecedentes de alergias o de traumatismos durante el coito o la masturbación. Se midieron los niveles totales de IgE. Resultados. Se incluyeron 27 pacientes en el estudio. Todos habían recibido un diagnóstico clínico. La media de edad fue de 36 (22-54). El tiempo transcurrido desde la última relación sexual o masturbación y la aparición de los síntomas de 3 días de media (1-10). Los síntomas surgieron en menos de 24 horas para 6 pacientes. Los síntomas aparecieron antes de manera estadísticamente significativa en aquellos pacientes con antecedentes de coito o masturbación traumáticos (p: 0,0046). El nivel de IgE en sangre fue superior al valor de referencia en 8 pacientes (30%). Los síntomas aparecieron más tarde con significación estadística en los pacientes con niveles de IgE altos (p: 0,0004). Conclusión. Existen motivos inmunológicos, traumáticos e infecciosos que ocasionan la linfangitis del surco coronario. En el presente estudio se considera que la tasa de pacientes que contaban con motivos inmunológicos ascendía al 30% (AU)

Changes in Antibody Levels during and following an Episode of Acute Adenolymphangitis (ADL) among Lymphedema Patients in Léogâne, Haiti.

INTRODUCTION: Episodes of acute adenolymphangitis (ADL) are often the first clinical sign of lymphatic filariasis (LF). They are often accompanied by swelling of the affected limb, inflammation, fever, and general malaise and lead to the progression of lymphedema. Although ADL episodes have been studied for a century or more, questions still remain as to their etiology. We quantified antibody levels to pathogens that potentially contribute to ADL episodes during and after an episode among lymphedema patients in Léogâne, Haiti. We estimated the proportion of ADL episodes hypothesized to be attributed to specific pathogens. METHODS: We measured antibody levels to specific pathogens during and following an ADL episode among 41 lymphedema patients enrolled in a cohort study in Léogâne, Haiti. We calculated the absolute and relative changes in antibody levels between the ADL and convalescent time points. We calculated the proportion of episodes that demonstrated a two-fold increase in antibody level for several bacterial, fungal, and filarial pathogens. RESULTS: Our results showed the greatest proportion of two-fold changes in antibody levels for the carbohydrate antigen Streptococcus group A, followed by IgG2 responses to a soluble filarial antigen (BpG2), Streptococcal Pyrogenic Exotoxin B, and an antigen for the fungal pathogen Candida. When comparing the median antibody level during the ADL episode to the median antibody level at the convalescent time point, only the antigens for Pseudomonas species (P-value = 0.0351) and Streptolysin O (P-value = 0.0074) showed a significant result. CONCLUSION: Although our results are limited by the lack of a control group and few antibody responses, they provide some evidence for infection with Streptococcus A as a potential contributing factor to ADL episodes. Our results add to the current evidence and illustrate the importance of determining the causal role of bacterial and fungal pathogens and immunological antifilarial response in ADL episodes.

Inmunoterapia sublingual en el tratamiento de la linfangitis recidivante / Sublingual Immunotherapy in the treatment of relapsing Lymphangitis

Se plantea actualmente que la inmunoterapia sublingual activa los mecanismos inmunoreguladores, a través del drenaje hacia los ganglios linfáticos regionales, por lo que no parecen existir razones teóricas para dudar del potencial de esta vía de liberación antigénica para la inmunoterapia. Como método se realizaron cuantificación de inmonogloibulinas y de inmunocomplejos circulantes, encontrándose los mismos dentro del rango de los valores normales... En función de los resultados obtenidos, los autores concluyen que la inmunoterapia sublingual con extractos bacterianos puede ser una alternativa válida para el tratamiento de la linfangitis recidivante

Inmunoterapia sublingual en el tratamiento de la linfangitis recidivante / Sublingual Immunotherapy in the treatment of relapsing Lymphangitis

Se plantea actualmente que la inmunoterapia sublingual activa los mecanismos inmunoreguladores, a través del drenaje hacia los ganglios linfáticos regionales, por lo que no parecen existir razones teóricas para dudar del potencial de esta vía de liberación antigénica para la inmunoterapia. Como método se realizaron cuantificación de inmonogloibulinas y de inmunocomplejos circulantes, encontrándose los mismos dentro del rango de los valores normales... En función de los resultados obtenidos, los autores concluyen que la inmunoterapia sublingual con extractos bacterianos puede ser una alternativa válida para el tratamiento de la linfangitis recidivante

A case of sclerosing lymphangitis of the lip.

A 62-year-old woman noted a cord-like swelling on the inner surface of her upper lip. A cross-section of the lesion showed a radial-shaped lumen surrounded by a thickened fibrous wall. Immunohistochemical staining with the anti-factor VIII-related antigen (FVIII-RAg) antibody was negative on the luminal surface and swollen wall, although the vasa vasorum in the swollen wall were positive. The lesion was thus considered to be of lymphatic origin; that is, it derived from a lymphatic collecting vessel. For the present case, the term 'lymphangiopathia obliterans' is considered appropriate. This is the second report of such a lesion appearing on the lip in the literature.

Pulmonary involvement in infectious mononucleosis: histopathologic features and detection of Epstein-Barr virus-related DNA sequences.

Symptomatic pulmonary parenchymal involvement is rare in infectious mononucleosis, and few pathologic descriptions of this lesion exist. We describe an unusual patient who presented with adenopathy and rapidly progressive interstitial lung disease. An open lung biopsy showed a predominantly interstitial infiltrate of mononuclear cells distributed along lymphatic routes. A patchy alveolar exudate was also seen. Biopsy of a paratracheal lymph node showed paracortical hyperplasia typical of infectious mononucleosis. The diagnosis was suspected only after thoracotomy and was established by appropriate serological studies for Epstein-Barr virus. Epstein-Barr virus genomic sequences were also detected within routinely processed lung and lymph node tissues using polymerase chain reaction technology. Infectious mononucleosis should be considered in the differential diagnosis of certain lymphoid lung lesions.

Algunos aspectos del pérfil inmunológico de pacientes linfangíticos / Some aspects of the immunologic profile of patients suffering lymphangitis

Se estudió un total de 75 pacientes linfangíticos a los cuales se les realizaron determinaciones de distintos parámetros del sistema inmune que incluyó: niveles de inmunoglobulina IgG, IgA e IgM, nivel del sistema complemento, porcentaje de células T y B en sangre periférica y adherencia leucocitaria. Entre los pacientes se encontró una elevación significativa de los niveles de IgM y complemento hemolítico y una disminución significativa del porcentaje de células B y de la adherencia leucocitaria al compararlos con un grupo control de promedio de edad comparable. No pudo establecerse una relación entre el estado clínico del paciente o de la recurrencia de las crisis con los valores obtenidos, aunque el grupo que padeció el mayor número de crisis por año tuvo las cifras más bajas para la adherencia leucocitaria

Algunos aspectos del pérfil inmunológico de pacientes linfangíticos / Soe aspects of the immunologic profile of patients suffering lymphangitis

Se estudió un total de 75 pacientes linfangíticos a los cuales se les realizaron determinaciones de distintos parámetros del sistema inmune que incluyó: niveles de inmunoglobulina IgG, IgA e IgM, nivel del sistema complemento, porcentaje de células T y B en sangre periférica y adherencia leucocitaria. Entre los pacientes se encontró una elevación significativa de los niveles de IgM y complemento hemolítico y una disminución significativa del porcentaje de células B y de la adherencia leucocitaria al compararlos con un grupo control de promedio de edad comparable. No pudo establecerse una relación entre el estado clínico del paciente o de la recurrencia de las crisis con los valores obtenidos, aunque el grupo que padeció el mayor número de crisis por año tuvo las cifras más bajas para la adherencia leucocitaria

Immune reactions to Wuchereria bancrofti infections in Tanzania. I. Serum-mediated adherence of leucocytes to microfilariae in vitro, using serum from different groups of patients.

Studies on serum-mediated adherence of leucocytes to microfilariae of Wuchereria bancrofti in vitro were carried out in an area of Tanzania endemic for filarial infections. Patients were divided into age-matched groups according to parasitological and clinical conditions. No adherence was seen with serum from microfilariae-positive patients (with or without clinical disease). A slightly, but not statistically significantly, higher prevalence of adherence-positive sera was found among hydrocele patients (27%) and lymphangitis/elephantiasis patients (33%) than among endemic control patients (20%). These three positive groups exhibited a marked difference in age distribution of prevalence of positivity, with very high prevalences found among young hydrocele patients (48%) and old lymphangitis/elephantiasis patients (63%). The hydrocele fluid from hydrocele patients with adherence-positive serum also mediated adherence.

Immune reactions to Wuchereria bancrofti infections in Tanzania. II. Characterization of the serum-mediated adherence reaction of leucocytes to microfilariae in vitro.

Investigations to characterize the in vitro reaction of serum-mediated leucocyte-adherence to microfilariae of Wuchereria bancrofti were carried out in Tanzania. The adherence reaction took place within one hour and at least two serum factors were involved: a heat-labile factor, present also in normal serum (probably complement), and a more heat-stable factor, present in positive serum only (probably an antibody). Neutrophils and eosinophils were involved in the reaction proportionately to Their numbers in the cell solutions used; the reaction killed significantly more microfilariae, than did adherence-negative tests. Microfilariae could be used for at least one week after their isolation from the donor, but a significant decrease in the percentage of reactive microfilariae occurred within 16 hours of isolation. A high degree of species specificity was observed when positive sera were tested against other nematodes. The involvement of complement and the speed with which the reaction took place is in contrast to the results of similar studies from India, and may indicate a difference in the parasite in the two continents.

Cyclic pharyngeal lymphoiditis: immunological considerations.

This communication presents the concept that recurrent infections of the lingual tonsils, lateral pharyngeal lymphoid bands and lymphoid follicles on the posterior pharyngeal wall, occurring with the same periodicity, is a cyclic clinical and immunological entity. These patients lacked resistance to the normal flora of the nasopharynx and pharynx. They were accordingly treated with a mixed respiratory bacterial vaccine, administered intradermally and according to a formulated program, to improve resistance or immunity of the lymphoid tissue. These patients showed definite improvement by this method of therapy. It is suggested that the effectiveness of therapy was accomplished through the immunological process of cell-mediated immunity. The immunobiologic development of cell-mediated immunity by T thymic-dependent cells and humoral immunity by B cells is briefly discussed.