The Scribble Complex PDZ Proteins in Immune Cell Polarities.

hScrib and hDlg belong to the PDZ family of proteins. Since the identification of these highly phylogenetically conserved scaffolds, an increasing amount of experiments has elucidated the roles of hScrib and hDlg in a variety of cell functions. Remarkably, their participation during the establishment of polarity in epithelial cells is well documented. Although the role of both proteins in the immune system is scantly known, it has become a growing field of investigation. Here, we summarize the interactions and functions of hScrib and hDlg1, which participate in diverse functions involving cell polarization in immune cells, and discuss their relevance in the immune cell biology. The fundamental role of hScrib and hDlg1 during the establishment of the immunological synapse, hence T cell activation, and the recently described role of hScrib in reactive oxygen species production in macrophages and of hDlg1 in cytokine production by dendritic cells highlight the importance of both proteins in immune cell biology. The expression of these proteins in other leukocytes can be anticipated and needs to be confirmed. Due to their multiple interaction domains, there is a wide range of possible interactions of hScrib and hDlg1 that remains to be explored in the immune system.

Immunization of BALB/c mice with pigeon IgY induces the production of anti-IgG autoantibodies.

The breakdown of immunological tolerance due to the activation of autoreactive B and T cells triggers physiopathological processes. An example of such conditions is the production of IgG autoantibodies specific for the Fc portion of IgG (anti-Fcγ IgG). Previous reports have shown that patients with pigeon-related hypersensitivity pneumonitis exhibit an increase in the serum levels of anti-Fcγ IgG. There is no in vivo model for the study of this condition and the immunological mechanisms of tolerance breakdown associated with sensitization by pigeon antigens are still unknown. In this work, we show that the repeated immunization of BALB/c mice with pigeon IgY during 16-weeks induces the production of anti-Fcγ IgG and keeps their high levels for seven weeks. The late appearance of anti-Fcγ IgG autoantibodies in the plasma is similar to what has been reported in other experimental autoimmune models. With the occurrence of anti-Fcγ IgG, there is a reduction in the proportion of Foxp3 + cells (regulatory T cells, Tregs) within the population of splenic CD4 + CD25 + T cells. Thus, our data showed that the immunization of BALB/c mice with IgY promotes the production of anti-Fcγ IgG along with a decrease in Tregs in the spleen. We propose that immunization of mice with pigeon antigens, like IgY can provide a model to study the immunological mechanisms involved in the development of pigeon-related hypersensitivity pneumonitis.

Airway Hyperresponsiveness in Asthma Model Occurs Independently of Secretion of ß1 Integrins in Airway Wall and Focal Adhesions Proteins Down Regulation.

The extracellular domains of some membrane proteins can be shed from the cell. A similar phenomenon occurs with ß1 integrins (α1ß1 and α2ß1) in guinea pig. The putative role of ß1 integrin subunit alterations due to shedding in airway smooth muscle (ASM) in an allergic asthma model was evaluated. Guinea pigs were sensitized and challenged with antigen. Antigenic challenges induced bronchoobstruction and hyperresponsiveness at the third antigenic challenge. Immunohistochemistry and immunoelectronmicroscopy studies showed that the cytosolic and extracellular domains of the ß1 integrin subunit shared the same distribution in airway structures in both groups. Various polypeptides with similar molecular weights were detected with both the cytosolic and extracellular ß1 integrin subunit antibodies in isolated airway myocytes and the connective tissue that surrounds the ASM bundle. Flow cytometry and Western blot studies showed that the expression of cytosolic and extracellular ß1 integrin subunit domains in ASM was similar between groups. An increment of ITGB1 mRNA in ASM was observed in the asthma model group. RACE-PCR of ITGB1 in ASM did not show splicing variants. The expression levels of integrin-linked kinase (ILK) and paxillin diminished in the asthma model, but not talin. The levels of phosphorylation of myosin phosphatase target subunit 1 (MYPT1) at Thr(696) increased in asthma model. Our work suggests that ß1 integrin is secreted in guinea pig airway wall. This secretion is not altered in asthma model; nevertheless, ß1 integrin cytodomain assembly proteins in focal cell adhesions in which ILK and paxillin are involved are altered in asthma model. J. Cell. Biochem. 117: 2385-2396, 2016. © 2016 Wiley Periodicals, Inc.

Neutrophilia induced by histamine challenge in guinea pig: The role of IL-5, IL-10 and IL-17A, but not CXCL8

Background: Histamine is widely used as a pharmacological tool for the evaluation of airway responsiveness. Nevertheless, undesirable and contradictory effects have been described after histamine provocation tests. In previous evaluations of airway responsiveness in a guinea pig asthma model, the control groups consistently showed high neutrophil counts in bronchoalveolar lavage fluid (BALF) immediately after the histamine challenge. The changes in cytokine and chemokine levels in guinea pig lung associated with histamine induced-neutrophilia are described in this paper. Methods: Immediately and 24 h after histamine challenge, airway wall and BALF eosinophil and neutrophil counts as well as lung cytokines (IL-5, IL-10, IL-17A, TNFα and TGFβ) and chemokines (CCL11 and CXCL8) levels were evaluated. Results: Histamine inhalation generated an all-or-none bronchial response, and the dose inducing airway obstruction was similar in all guinea pigs. Immediate increases in neutrophil counts in airway wall and BALF and in IL-5, IL-10 and IL-17A levels in the lung homogenate were observed after histamine challenge. Significant correlations were found between neutrophil counts from airway wall and IL-5, IL-10 and IL-17A levels in the lung homogenate. Conclusions: Histamine inhalation induced rapid neutrophil LBA and airway wall infiltration that was not associated with CXCL8 expression but with a Th2 and Th17 cytokines that probably are involved in the recruitment and activation of neutrophils.

Antigen-induced airway hyperresponsiveness in absence of broncho-obstruction in sensitized guinea pigs.

BACKGROUND: Airway obstruction after antigen challenge is not always observed in patients with allergic asthma, even if they develop hyperresponsiveness. A similar event is observed in our guinea pig model of allergic asthma. Our aim was to study this phenomenon. METHODS: Sensitized guinea pigs were challenged with ovalbumin (OVA) 3 times every 10 days. Animals were divided into 2 groups: (1) Guinea pigs exhibiting airway obstruction after antigen challenge (R = responders), and (2) guinea pigs lacking airway obstruction response (NR = nonresponders). After the third antigen challenge, antigen-induced airway hyperresponsiveness (AI-AHR), serum OVA-specific immunoglobulins, bronchoalveolar lavage fluid (BALF) inflammatory cells, histamine, cysteinyl leukotrienes and thromboxane A2 (TxA2) BALF levels, and in vitro tracheal contraction induced by contractile mediators and OVA were evaluated. RESULTS: R group consistently displayed a transient antigen-induced airway obstruction (AI-AO) as well as AI-AHR, high T×A2, histamine, OVA-IgG1, OVA-IgE and OVA-IgA levels, and intense granulocyte infiltration. NR group displayed no AI-AO and no changes in BALF measurements; nevertheless, AI-AHR and elevated OVA-IgG1 and OVA-IgA levels were observed. In all groups, histamine, TxA2 and leukotriene D4 induced a similar contraction. Tracheal OVA-induced contraction was observed only in R group. AI-AHR magnitude showed a direct association with OVA-IgG1 and OVA-IgA levels. The extent of AI-AO correlated directly with OVA-IgE and inversely with OVA-IgA levels. CONCLUSIONS: Our data suggest that TxA2 and histamine participate in AI-AO likely through an IgE mechanism. AI-AHR might occur independently of AI-AO, contractile mediators release, and airway inflammatory cell infiltration, but IgA and IgG1 seem to be involved.

[Plasmablastic lymphoma of the gastrointestinal tract in AIDS patients]. / Linfomas plasmoblásticos del tracto gastrointestinal en pacientes con sida.

The risk of developing non-Hodgkin lymphoma (NHL) is 200 times higher in HIV-positive patients than otherwise healthy persons. Plasmablastic lymphoma (PL) represents < 3% of all NHL associated with HIV infection. The aim of this study was to review the clinical-pathologic features of PL of the gastrointestinal tract in 5 patients with HIV/aids disease. We performed a retrospective study of PL of the gastrointestinal tract diagnosed at the National Institute of Cancer at Mexico City, from 2000 to 2009. Clinical and pathological information was obtained and immunohistochemical studies were performed in paraffin-embedded tissue sections. The presence of Epstein-Barr Virus (EBV) was examined by in situ polymerase chain reaction (PCR). Four male and 1 female were included with a median of age of 29 years. Three tumors involved the ano-rectal area, one tumor the ascendant colon and one tumor the stomach. All tumors were histologically characterized by a monotonous proliferation of large lymphoid cell with plasmablastic features. Tumor cells were CD 138 / MUM-1 positive and CD 20 / PAX-5 negative in all cases. EVB genome was detected by in situ PCR in 4 cases. The median of follow-up was 18 months, and revealed that three patients are alive with neoplasm disease and two patients are still alive with no evidence of the neoplasm. Recognition of this entity by pathologists and clinicians is important in order to establish the correct diagnosis and the early treatment of these patients.

Linfomas plasmoblásticos del tracto gastrointestinal en pacientes con sida / Plasmablastic lymphoma of the gastrointestinal tract in AIDS patients

Los pacientes con infección por el virus de inmunodeficiencia humana (HIV) tienen 200 veces más riesgo de desarrollar un linfoma no Hodgkin (LNH) con respecto a la población general. El linfoma plasmoblástico (LP) representa menos del 3% de todos los LNH asociados con el HIV. El objetivo de este estudio es informar las características clínico-patológicas de 5 pacientes con enfermedad HIV/sida y LP del tracto gastrointestinal. Se revisaron de forma retrospectiva los casos de LP del tracto gastrointestinal diagnosticados en el Instituto Nacional de Cancerología de la Ciudad de México en el periodo comprendido entre los años 2000 al 2009. Se analizaron las características clínico-patológicas y se realizaron cortes de bloques de tejidos embebidos en parafina para reacciones de inmunohistoquímica. La presencia del virus de Epstein Barr (VEB) se examinó por reacción en cadena de la polimerasa (PCR) in situ. De los cinco pacientes, cuatro fueron hombres y una mujer, con una mediana de edad de 29 años. Tres tumores se localizaron en la región anorrectal, uno en colon ascendente y el restante en el estómago. Histológicamente, todos los tumores se caracterizaron por una proliferación difusa de células grandes de aspecto plasmoblástico. Las células neoplásicas fueron CD 138/MUM-1 positivas y CD 20 / PAX-5 negativas. En cuatro pacientes se detectó el genoma del VEB en las células neoplásicas mediante PCR in situ. La mediana de seguimiento fue 18 meses; tres pacientes estaban vivos con enfermedad y dos sobreviven sin evidencias de la neoplasia. El diagnóstico precoz de LP como una entidad clínico-patológica es importante para establecer el tratamiento correcto y mejorar el pronóstico de estos pacientes.

The risk of developing non-Hodgkin lymphoma (NHL) is 200 times higher in HIV-positive patients than otherwise healthy persons. Plasmablastic lymphoma (PL) represents < 3% of all NHL associated with HIV infection. The aim of this study was to review the clinical-pathologic features of PL of the gastrointestinal tract in 5 patients with HIV/aids disease. We performed a retrospective study of PL of the gastrointestinal tract diagnosed at the National Institute of Cancer at Mexico City, from 2000 to 2009. Clinical and pathological information was obtained and immunohistochemical studies were performed in paraffin-embedded tissue sections. The presence of Epstein-Barr Virus (EBV) was examined by in situ polymerase chain reaction (PCR). Four male and 1 female were included with a median of age of 29 years. Three tumors involved the ano-rectal area, one tumor the ascendant colon and one tumor the stomach. All tumors were histologically characterized by a monotonous proliferation of large lymphoid cell with plasmablastic features. Tumor cells were CD 138 / MUM-1positive and CD 20 / PAX-5 negative in all cases. EVB genome was detected by in situ PCR in 4 cases. The median of follow-up was 18 months, and revealed that three patients are alive with neoplasm disease and two patients are still alive with no evidence of the neoplasm. Recognition of this entity by pathologists and clinicians is important in order to establish the correct diagnosis and the early treatment of these patients.

Aerosolized polymerized type I collagen reduces airway inflammation and remodelling in a guinea pig model of allergic asthma.

Collagen-polyvinylpyrrolidone (Collagen-PVP) has been demonstrated to elicit immunomodulatory properties in different chronic inflammatory diseases. Nevertheless, its effects on asthma are still unknown. We have evaluated whether collagen-PVP could modulate airway inflammation and remodelling in a guinea pig model of allergic asthma. Sensitized guinea pigs were challenged with the allergen (ovalbumin) six times (at 10-day intervals). From the third challenge on, animals were treated every 5 days with saline aerosols containing 0.16, 0.33, or 0.66 mg/ml of collagen-PVP (n = 5, respectively). Some guinea pigs, sensitized and challenged with saline as well as treated with 0 or 0.66 mg/ml collagen-PVP, were included in the study as control (n = 7) and sham groups (n = 5), respectively. From the first challenge on, ovalbumin induced a transient airway obstruction, measured by barometric plethysmography, which was not modified by collagen-PVP treatments. After the last allergen challenge, guinea pigs were anesthetized to obtain bronchoalveolar lavage (BAL) and the left lung caudal lobe. As expected, BAL cell count from allergen-challenged guinea pigs showed abundant neutrophils and eosinophils, as well as numerous tumor necrosis factor (TNF)-alpha-expressing granulocytes and macrophages in airway wall (determined by immunohistochemical assay). Neutrophilia and TNF-alpha-expressing leukocytes, from collagen-PVP treated animals, diminished from 0.16 mg/ml, and eosinophilia from 0.66 mg/ml of collagen-PVP doses. Histological changes induced by allergen challenges include thickening of connective tissue below airway epithelium and vascular wall widening of airway adjacent vessels; these changes were reduced by collagen-PVP treatment. Collagen-PVP seems to have anti-inflammatory and antifibrotic properties in this guinea pig asthma model.

IgM, IgG, and IgA anti-DNA topoisomerase I antibodies in systemic sclerosis.

BACKGROUND: Anti-DNA topoisomerase I (anti-topo I) antibodies have been broadly studied in systemic sclerosis (SSc). The use of different native and molecularly cloned antigens has shown a predominant IgG response, and a variable frequency of positive IgM and IgA tests. We report herein the serological findings of SSc using a recombinant topo I obtained through a standard bacterial system. METHODS: Anti-topo I antibodies were studied in 45 SSc patients and 85 healthy controls through ELISA and western blot. Escherichia coli XL1-blue strain and pT7-7 vector were used to amplify a DNA topo I cDNA clone, and to obtain the recombinant polypeptide. The latter was purified by affinity chromatography, and the enzymatic and antigenic properties were evaluated through specific tests. A native antigen was included for comparison. RESULTS: The SSc group disclosed positive IgM (20%), IgG (86.6%), and IgA (26.6%) anti-topo I tests with the recombinant polypeptide, and a purified calf thymus antigen yielded similar results. IgG autoantibodies were frequently associated with skin involvement, esophageal dysfunction, and restrictive lung disease. The recombinant protein showed a molecular weight of 86.6 kDa, a positive topo I activity using a supercoiled pBR322 DNA relaxation test, and its carboxyl terminus region was recognized by specific antibodies. CONCLUSION: This report confirms that different immunoglobulin classes with anti-topo I activity may occur in SSc. IgG was the predominant serological feature with both, the recombinant and native antigens. The study also demonstrates the association between high levels of these autoantibodies and some clinical manifestations of SSc.

IgM, IgG, and IgA rheumatoid factors in pigeon hypersensitivity pneumonitis.

The association of rheumatoid factor (RF) and lung disease in several immunologically mediated conditions has suggested that it may be physiopathologically relevant. Since previous reports in hypersensitivity pneumonitis (HP) have dealt mainly with the immunoglobulin M (IgM) RF measurement, we studied such antibody activity in other immunoglobulins, to determine the IgG and IgA RF levels in pigeon-HP, and in asymptomatic breeders (AB) and rheumatoid arthritis (RA) as controls. RFs were measured in 35 HP patients, 41 AB, 31 RA controls, and 55 healthy donors by enzyme-linked immunosorbent assay (ELISA) using human or rabbit immunoglobulin G (IgG), anti-IgM, F(ab')2 of IgG, and IgA F(ab')2 conjugates. An affinity chromatography, fragment crystallizable (Fc) preparations of IgG, pepsin digestion, and Western blots were used to confirm RF specificity. We also evaluated anti-avian antibodies (AA) and cross-reacting antibodies. The HP group revealed positive IgM (51.4%), IgG (31.4%), and immunoglobulin A (IgA) (34.2%) RF tests, and these antibody values exceeded the AB reference levels (P<0.02). HP and RA showed a similar frequency and distribution of RFs. Possible immunoassay interferences were excluded. As in other immunologically mediated diseases, IgG and IgA RFs may play a pathogenic role in HP, amplifying the inflammatory reaction, immune-complex formation, and complement activation. IgM-RF producing cells that have been implicated in the presentation of self and foreign antigens, and T-cell activation might induce the isotype switching of RFs.

Pigeon hypersensitivity pneumonitis: immunohistochemical demonstration of the causative antigen in the lung.

A number of clinicopathological manifestations may define the presence of hypersensitivity pneumonitis. Histological study is used to establish the diagnosis and to differentiate the disease from other respiratory disorders. This case report suggests that immunohistological demonstration of the causative antigen in the lung may be a useful diagnostic approach in cases of pigeon hypersensitivity pneumonitis. A 52 year-old woman was studied. She had a prior history of pigeon exposure, and lived in an area with a high prevalence of tuberculosis. Her clinical presentation, respiratory function tests and imaging studies revealed a predominant interstitial lung disease. The results of antiavian antibodies, bronchoalveolar analysis, and other laboratory parameters were non-diagnostic. A lung biopsy showed a prominent granulomatous reaction with a sarcoid-like appearance in some areas, and an interstitial infiltration constituted by lymphocytes, plasma cells and foamy macrophages. Although the disease manifestations were compatible with hypersensitivity pneumonitis, we decided to study the causal antigen by immunohistochemistry. The use of a polyclonal antibody raised against pigeon serum showed a predominant cytoplasmic immunostaining in multinucleated giant cells and histiocytes from lung granulomas. Other respiratory disorders were reasonably excluded. Previous exposure to a known antigen may support the diagnosis of hypersensitivity pneumonitis. Although the inhalation of organic dusts may be clinically evident, the aetiology is commonly evaluated by different challenge tests or immunological methods. We propose that the study of pigeon antigen by immunohistochemistry may be used as part of the diagnostic approach for hypersensitivity pneumonitis.

Expression of cyclooxygenase-2, alpha 1-acid-glycoprotein and inducible nitric oxide synthase in the developing lesions of murine leprosy.

Murine leprosy is a chronic disease of the mouse, the most popular animal model used in biomedical investigation, which is caused by Mycobacterium lepraemurium (MLM) whose characteristic lesion is the macrophage-made granuloma. From onset to the end of the disease, the granuloma undergoes changes that gradually transform the environment into a more appropriate milieu for the growth of M. lepraemurium. The mechanisms that participate in the formation and maturation of the murine leprosy granulomas are not completely understood; however, microbial and host-factors are believed to participate in their formation. In this study, we analysed the role of various pro-inflammatory and anti-inflammatory proteins in granulomas of murine leprosy after 21 weeks of infection. We assessed the expression of cyclooxygenase-2 (COX-2), alpha acid-glycoprotein (AGP), and inducible nitric oxide synthase (iNOS) at sequential stages of infection. We also looked for the nitric-oxide nitrosylation product, nitrotyrosine (NT) in the granulomatous lesions of murine leprosy. We found that a pro-inflammatory environment predominates in the early granulomas while an anti-inflammatory environment predominates in late granulomas. No obvious signs of bacillary destruction were observed during the entire period of infection, but nitrosylation products and cell alterations were observed in granulomas in the advanced stages of disease. The change from a pro-inflammatory to an anti-inflammatory environment, which is probably driven by the bacillus itself, results in a more conducive environment for both bacillus replication and the disease progression.

LTD4 induces hyperresponsiveness to histamine in bovine airway smooth muscle: role of SR-ATPase Ca2+ pump and tyrosine kinase.

Airway hyperresponsiveness is a key feature of asthma, but its mechanisms remain poorly understood. Leukotriene D(4) (LTD(4)) is one of the few molecules capable of producing airway hyperresponsiveness. In this study, LTD(4), but not leukotriene C(4) (LTC(4)), produced a leftward displacement of the concentration-response curve to histamine in bovine airway smooth muscle strips. Neither LTC(4) nor LTD(4) modified the concentration-response curve to carbachol. In simultaneous measurements of intracellular Ca(2+) ([Ca(2+)](i)) and contraction, histamine or carbachol produced a transient Ca(2+) peak followed by a plateau, along with a contraction. LTD(4) increased the histamine-induced transient Ca(2+) peak and contraction but did not modify responses to carbachol. Enhanced responses to histamine induced by LTD(4) were not modified by staurosporine or chelerythrine but were abolished by genistein. Western blot showed that carbachol, but not histamine, caused intense phosphorylation of extracellular signal-regulated kinase 1/2 and that LTD(4) significantly enhanced the phosphorylation induced by histamine, but not by carbachol. L-type Ca(2+) channel participation in the hyperresponsiveness to histamine was discarded because LTD(4) did not modify the [Ca(2+)](i) changes induced by KCl. In tracheal myocytes, LTD(4) enhanced the transient Ca(2+) peak induced by histamine (but not by carbachol) and the sarcoplasmic reticulum (SR) Ca(2+) refilling. Genistein abolished this last LTD(4) effect. Partial blockade of the SR-ATPase Ca(2+) pump with cyclopiazonic acid reduced the Ca(2+) transient peak induced by histamine but not by carbachol. These results suggested that LTD(4) induces hyperresponsiveness to histamine through activation of the tyrosine kinase pathway and an increasing SR-ATPase Ca(2+) pump activity. L-type Ca(2+) channels seemed not to be involved in this phenomenon.

Citocinas en médula ósea de pacientes con linfoma no Hodgkin: estudio por RT-PCR y revisión de la literatura / Cytocines in patientïs Osseous marrow presenting Non-Hodgkin Lymphoma

El conocimiento de las interacciones que se llevan a cabo entre los precursores y progenitores sanguíneos con los componentes estromales y los factores solubles en la médula ósea (MO), ha sido la base para estudiar la existencia de anormalidades específicas en el microambiente hematopoyético. En neoplasias hematológicas como el linfoma no Hodgkin (LNH) se desconoce si existen anormalidades en cuanto a la producción de citocinas en la MO y si éstas pueden afectar el desarrollo de los progenitores linfoides predisponiéndolos a la neoplasia. Mediante el empleo de retrotranscripción y la reacción en cadena de la polimerasa (RT-PCR) se estudió la expresión de citocinas supresoras de la hematopoyesis como interleucina-10 (IL-10), factor de necrosis tumoral a (TNF-a) e interferon g (IFN-g) en aspirados de MO de 20 pacientes con LNH sin tratamiento previo. El grupo testigo incluyó 19 individuos clínicamente sanos pertenecientes al programa de trasplante de MO. También se determinó la expresión de TGF-b en 15 pacientes y 15 testigos mediante la misma técnica. La extracción de ARN se realizó con el método de isotiocianato de guanidina y el ADNc fue obtenido por retrotranscripción. La amplificación por PCR se realizó con Taq ADN-polimerasa y oligonucleótidos específicos para cada citocina y b-actina empleada como testigo interno de la síntesis de ADNc. El análisis estadístico se realizó mediante la prueba exacta de Fisher. Se encontró una disminución en la expresión de TNF-a (p= 0.001) y TGF-b (p= 0.001) en LNH comparado con el grupo testigo. En cambio, no se observó una diferencia significativa en la presencia de IL-10 e IFN-g entre ambos grupos. Los resultados obtenidos sugieren una expresión anormal de citocinas inhibitorias en la MO, lo que podría conducir a: 1) defectos en la diferenciación y desarrollo anormal de las células progenitoras, 2) un desbalance de los mecanismos hematopoyéticos que regulan el crecimiento celular y 3) escape de las células anormales a la apoptosis, favoreciendo la transformación neoplásica de las células linfoides y sus progenitores en linfoma no Hodgkin.

Detección de factor reumatoide por nefelometría en pacientes de un centro hospitalario en México / Determination of rheumatoid factor by nephelometry in a mexican medical center

Se estudió la presencia de factor reumatoide por nefelometría en 6.264 muestras consecutivas de suero, provenientes de pacientes captados de una población hospitalaria de 1988 a 1990. El 52 por ciento de estos pacientes presentaron FR positivo, en comparación con el 1,4 por ciento en el grupo control. Se obtuvieron resultados negativos en 48 por ciento de los sueros captados en población hospitalaria, en comparación al 98 por ciento de muestras negativas en una población control (p<0,000001), captada en una clínica de atención de primer nivel. Ambos grupos mostraron características demográficas y socioeconómicas similares y los resultados no dependieron del número de pacientes estudiados, cuando se divieron a los resultados en negativos (<30Ul/ml), intermedios (30-110 Ul/ml) y altos (>30 Ul/ml), se encontró una frecuencia similar de los sueros positivos (20-27 por ciento), especialmente cuando se evaluaron los límites intermedios. Estos niveles variaron muy poco en los diferentes períodos del estudio. Los resultados de factor reumatoide pueden mostrar gran variación de acuerdo a la edad, sexo, antecedentes inmunogenéticos, o antecedentes patológicos en diferentes poblaciones. Los pacientes de población hospitalaria, muestran una alta incidencia de padecimientos infecciosos e inflamatorios crónicos que pueden cursar con pruebas positivas para factor reumatoide, y esto puede explicar su alta frecuencia en comparación con el grupo control. Falta definir la participación de ésta y otras variables en estudios posteriores

Alteraciones en lavado bronquialveolar de pacientes con artritis reumatoide / Alterations of bronchioalveolar lavage in patients with reumatoid arthritis

Estudiamos 16 pacientes con artritis reumatoide, sin evidencia clínica de patología pulmonar. la selección fue realizar mediante un estudio clínico radiológico y pruebas funcionales respiratorias. Una vez detectada la ausencia de alteraciones pulmonares se realizó broncoscopia y lavado bronquioalveolar. la cuenta celular mostró un incremento de los linfocitos o neutrófilos en 6 pacientes. ningún caso presentó simultáneamente ambas alteraciones. En cambio, 2 pacients presentaron un descenso del némero de macrófago en correlación con la elavoración de linfocitos y neutrófilos. La determinación de inmunoglobulinas por nefelometría, mostró elevación de IgG en 4 muestras, incremento de la IgM en 5 lavados y aumento de la IgA en 4 muestras. Sólo 4 de estos 9 enfermos, presentaron elevación de 2 inmunoglobulinas. Las alteraciones subclínicas detectadas por lavado bronquioalveolar puden evideniar los cambios que favorecen el desarrollo y progresión del daño pulmonar en la artritis reumatoide.

Autoanticuerpos en niños con enfermedades del tejido conjuntivo / Auto antibodies in children with connective tissue disease

El diagnóstico y clasificación de las enfermedades del tejido conjuntivo en los niños se ha basado principalmente en datos clínicos. Sin embargo, la adición de un número importante de hallazgos inmunológicos puede sustentar que en la infancia se presentan diferentes tipos y subgrupos de enfermedades autoinmunes. Los autoanticuerpos con diferentes especificidades definen no solo a distintos padecimientos sino también a diferentes subgrupos de pacientes con enfermedades del tejido conjuntivo. Esta revisión enfatiza que el factor reumatoide y los anticuerpos antinucleares son pruebas útiles que pueden ayudar a definir las características clínicas en niños con padecimientos reumáticos. El factor reumatoide de la clase IgM está presente frecuentemente en el grupo de pacientes con artritis reumatoide poliarticular, mientras que el grupo oligoarticular con uveitis tiene por características presentar una alta prevalencia de anticuerpos antinucleares. Los anticuerpos anti-DNA y anti-Sm son positivos en niños con lupus eritematoso generalizado. Los pacientes con dermatomiositis infantil tienen una menor frecuencia de anticuerpos contra los antígenos Jo-1 y PM-1, al compararlos con el grupo de polidermatomiositis del adulto. Los niños con esclerosis sistémica y síndome de CREST pueden mostrar anticuerpos anti-Scl-70 (topoisomerasa-1) y anticuerpos anti-centrómeto. Los títulos elevados de los anticuerpos anti RNpn (U1) parecen definir no sólo a la enfermedad mixta del tejido conjuntivo del adulto sino también a los niños. Los anticuerpos anti-SS-A (Ro) y anti-SS-B (La) han sido encontrados en pacientes con síndrome de Sjögren primario. Interesante otras anomalías, incluyendo a los anticuerpos antifosfolípidos, anti-proteínas hsp-70 y hsp-90, así como los anticuerpos contra productos contra oncogene-c-myc que han sido reportados en pacientes adultos con diferentes padecimietos del tejido conjuntivo, no han sido estudiados completamente en las enfermedades autoinmunes del niño. En suma los autoanticuerpos constituyen marcadores importantes que pueden ayudar a comprender lo complejo de la autoinmunidad en los niños.

Dermatomiositis del niño: estudio inmunológico / Childhool dermatomyositis: immunologic study

Estudiamos 8 niños con dermatomiositis con el objeto de detectar las anormalidades inmunológicas relacionadas al padecimiento. Las inmunoglobulinas séridas IgG, IgM e IgA, fueron determinadas por nefelometría, resultando normales en todos los casos, excepto en 2 enfermos, en quienes se notó un ligero incremento sin relación con la fase de actividad de la enfermedad. Sólo un paciente tuvo descenso de C4 asocaido a miopatía activa, pero no con vasculitis. No detectamos hipogamaglobulinemia y la prueba de VDRL fue negativa en todos los niños. El factor reumatoide fue positivo en 4 casos con títulos menores de 1:80 por la técnica de Waaler Rose. Los anticuerpos antinucleares por inmunofluorescencia indirecta estuvieron presentes en 5 niños, predominando el patrón moteado, resultados que no tuvieron relación con la exacerbación del padecimiento. No hubo anticuerpos anti-DNAn, o contra antígenos nucleares extraibles. Los anticuerpos anti-Jo-1, Mi-1 y Mi-2 fueron negativos. Los anticuerpos anti-toxoplasma de la clase IgG por la prueba de inmunofluorescencia indirecta estuvieron presentes en 7 pacientes. En ningún caso de encontró historia de toxoplasmosis ni datos de este padecimiento al momento del estudio o durante el seguimiento. Los anticuerpos anti-músculo liso fueron positivos en un caso. Ninguna de estas anormalidades mostró correlación con la actividad del padecimiento.