[Circulating populations of CD4+ CD25+ CD127- regulatory t lymphocytes in peripheral blood of allergic asthmatic children]. / Determinación de poblaciones circulantes en sangre periférica de linfocitos T, reguladores CD4+ CD25+ CD127-, en niños asmáticos alérgicos.

OBJECTIVE: To carry out a preliminary analysis on the Treg lymphocyte counts present in the peripheral blood of allergic asthmatic children from the city of Cartagena, Colombia, compared to healthy controls. METHODS: We compared cytometry counts of ten asthmatic patients (age 7-16 years) and seven healthy controls (6-12 years), recruited in the city of Cartagena. Peripheral blood samples were stained using Cytek's 14-color cFluor Immunoprofiling kit (Cytek® cFluor® Immunoprofiling Kit 14 Color RUO kit), and analyzed on a Northern Lights™ spectral cytometer (Cytek® Biosciences, Fremont, CA, USA), to read 50.000 events per sample. The data obtained were analyzed in SpectroFlo® and FlowJo. The study was approved by the ethics committee of the University of Cartagena (SGR, Grant BPIN2020000100405). RESULTS: The frequency of CD3+, CD4+, CD25+, CD127- Tregs was 11% of all CD4+ T cells, with a range of minimum 8,1% and maximum 17,7%. There was no significant difference in the proportion of Tregs between allergic asthmatic patients and healthy controls (P = 0,2). CONCLUSIONS: With this preliminary sample size, no significant differences were found in the Treg lymphocyte population between allergic asthmatic patients and healthy controls. The 14-color multiplexed panel is a useful tool not only to count CD3+ and CD4+ populations, but also to obtain the percentage of regulatory T cells using cell surface markers.

OBJETIVO: Realizar un análisis preliminar sobre los conteos de linfocitos Tregs presentes en sangre periférica de niños asmáticos alérgicos de la ciudad de Cartagena, comparado con controles sanos. MÉTODOS: Se compararon los conteos de citometría de diez pacientes asmáticos (entre 7 y16 años) y siete controles sanos (entre 6 y12 años), reclutados en la ciudad de Cartagena. La muestra de sangre periférica fue teñida empleando el kit de inmunofenotipo multiplexado de 14 colores de Cytek (Cytek® cFluor® Immunoprofiling Kit 14 Color), y analizada en un citómetro espectral Northern Lights™ (Cytek® Biosciences, Fremont, CA, USA), a lectura de 50.000 eventos por muestra. Los datos obtenidos fueron analizados en SpectroFlo® y FlowJo. El estudio fue aprobado por el Comité de Ética de la Universidad de Cartagena. RESULTADOS: El panel de tinción funcionó apropiadamente y dentro de los parámetros apropiados. Se obtuvo un promedio de células Tregs CD3+, CD4+, CD25+ y CD127- del 11% de todos los CD4+ en las muestras estudiadas, con un rango de mínimo de 8,1% y un máximo de 17,7%. No hubo diferencias significativas en la proporción de linfocitos Tregs entre los pacientes asmáticos alérgicos y los controles sanos (P = 0.2). CONCLUSIONES: Con este tamaño de muestra preliminar, no se encontraron diferencias significativas en la población de linfocitos Tregs entre los pacientes asmáticos alérgicos y los controles sanos. El panel multiplexado de 14 colores es una herramienta útil no solo para derivar las poblaciones CD3+ y CD4+, sino también para obtener el porcentaje de células T reguladoras empleando marcadores de superficie celular.

Reduction in the inflammatory markers CD4, IL-1, IL-6 and TNFα in dogs with keratoconjunctivitis sicca treated topically with mesenchymal stem cells.

Keratoconjunctivitis sicca (KCS) is of predominantly immune-mediated origin. Dogs are an excellent model for understanding this disease, as the origin of KCS in dogs is like that in humans. The objective of this study was to localize and quantify immunological markers, such as CD4 lymphocytes, interleukin (IL)-1, IL-6 and tumor necrosis factor alpha (TNFα), before and after topical treatment with mesenchymal stem cells (MSCs). Twenty-two dogs positive for KCS were topically treated with 50 µL (1 × 106 MSCs) in the conjunctival sac and were evaluated for 6 months. The levels of the markers CD4, IL-6, IL-1 and TNFα were analyzed in conjunctival biopsy and cytology of the third eyelid gland by immunohistochemistry and immunocytochemistry. The results showed that before treatment, there was marked expression of all the markers (CD4, IL-6, IL-1 and TNFα), and after 6 months, there were significant (p < .05) reductions in the expression levels of all the markers. These results demonstrated that topical MSC treatment promotes a significant decrease in the expression levels of these inflammatory markers and could be used as adjuvant therapy in the treatment of KCS in dogs and humans. In addition, these markers can be excellent tools for diagnosing and analyzing the progression of KCS.

Endocrine and metabolic function in male Carioca High-conditioned Freezing rats.

The aim of this study was to characterize Carioca High-conditioned Freezing rats (CHF) regarding their endocrine and metabolic backgrounds. We found an increase in serum corticosterone (CTRL: 96.7 ± 21.65 vs CHF: 292.0 ± 4 0.71 ng/ml) and leptin (CTRL: 9.5 ± 1.51 vs CHF: 19.2 ± 4.32 ng/ml). Serum testosterone (CTRL: 3.3 ± 0.29 vs CHF: 2.0 ± 0.28 ng/ml) and T3 (CTRL: 52.4 ± 2.74 vs CHF: 42.7 ± 2.94 ng/dl) were decreased in the CHF group, but serum TSH and T4 were unaffected. Body weight and food intake were unchanged, nevertheless retroperitoneal fat (CTRL: 2.2 ± 0.24 vs CHF: 4.8 ± 0.64 g) and epididymal fat (CTRL: 2.6 ± 0.20 vs CHF: 4.8 ± 0.37 g) depot weights were around 2-fold higher in CHF animals. BAT weight was similar in both groups. Serum triglycerides (CTRL: 41.4 ± 6.03 vs CHF: 83.2 ± 17.09 mg/dl) and total cholesterol (CTRL: 181.6 ± 5.61 vs CHF: 226.4 ± 13.04 mg/dl) were higher in the CHF group. Fasting glycemia (CTRL: 68.7 ± 3.04 vs CHF: 82.3 ± 2.99 mg/dl) was also higher in the CHF group, however glucose tolerance test response and serum insulin levels were similar between the groups. Oxygen consumption (CTRL: 10.5 ± 0.40 vs CHF: 7.9 ± 0.58 VO2ml/min/kg(0.75)) and BAT D2 activity (CTRL: 0.7 ± 0.17 vs CHF: 0.3 ± 0.04 fmolT4/min/mg ptn) were lower in the CHF group. Our data show that anxiety could impair endocrine and metabolic functions and may contribute to the development of metabolic diseases.

Analysis of Th1, Th17 and regulatory T cells in tuberculosis case contacts.

We have hypothesized that individuals infected with Mycobacteriumtuberculosis that exhibit different patterns of immune reactivity in serial interferon (IFN)-γ release assays (IGRA's) correspond to different status within the immune spectrum of latent tuberculosis (TB). Accordingly, we analyzed the possible association between the consistent results (negative or positive) in an IGRA test and relevant immune parameters, mainly the levels of Th1 and Th17 lymphocytes and T regulatory (Treg) cells in the peripheral blood of TB case contacts. We found that individuals with a persistently positive IGRA showed increased levels of Th1 and Th17 lymphocytes upon in vitro stimulation with MTB antigens. In addition, a significant increase in the proportion of CD4+CTLA-4+ and CD4+Foxp3+ cells was detected in assays with blood samples from these individuals. Our data support that different immune phenotypes can be identified into the spectrum of latent TB, by combining different parameters of immune reactivity against MTB.

The administration of milk fermented by the probiotic Lactobacillus casei CRL 431 exerts an immunomodulatory effect against a breast tumour in a mouse model.

Antitumour activity is one of the health-promoting effects attributed to probiotics specially analysed from preclinical models, mostly murine. Here, the effect of milk fermented by the probiotic bacterium Lactobacillus casei CRL 431, on a murine breast cancer model was analysed. Mice were fed with milk fermented by Lactobacillus casei or unfermented milk before and after tumour injection. Rate of tumour development, cytokines in serum, IgA, CD4, CD8, F4/80 and cytokines positive cells in mammary glands were determined. Microvasculature in the tumour tissues was monitored. The effect of fermented milk administration after tumour injection was also evaluated. It was observed that probiotic administration delayed or blocked tumour development. This effect was associated to modulation of the immune response triggered by the tumour. The area occupied by blood vessels decreased in the tumours from mice given fermented milk which agrees with their small tumours, and fewer side effects. Finally, it was observed that probiotic administration after tumour detection was also beneficial to delay the tumour growth. In conclusion, we showed in this study the potential of milk fermented by the probiotic Lactobacillus casei CRL431 to stimulate the immune response against this breast tumour, avoiding or delaying its growth when it was preventively administrated and also when the administration started after tumour cells injection.

Evaluation of late immunologic parameters among renal transplant recipients induced with Campath-1H.

Organ transplantation success depends principally on avoiding rejection, a purpose almost accomplished with immunosuppressant therapy. Nevertheless, drug side effects have promoted the search for other mechanisms to restrain alloresponses. T-regulatory cells (Treg) might exert that function. Campath 1H (C1H) induces Treg proliferation in the period subsequent to T-cell depletion following C1H administration. In the present study, the status of Treg and de novo HLA antibody production was determined posttransplantation when T-cell repopulation had been completed. In 14 patients, the following parameters were analyzed: renal function, rejection, Treg, panel-reactive antibody (PRA), and HLA antibodies. Patient and graft survivals were 100%. At the moment of Treg determination (20 months following transplant) the mean tacrolimus level was 8.4 ng/mL. One patient experienced an antibody-mediated rejection at 15 months after transplantation while having 3.2% Treg, with excellent treatment responses. Mean leukocyte and lymphocyte counts were 5752 and 1183 cells/mm(3); the mean peripheral blood percentage of Treg of 7.1% +/- 5.9% was not different from that observed in subjects without induction (mean 5.5% +/- 2.5%). Three patients (21%) showed Treg greater than 8.0%. In seven patients, we compared Treg at 4 and 20 months posttransplant, observing a decline from a mean of 19.9% to 5.9% (P = .05). In seven recipients, posttransplant PRA was determined; five of them became "de novo" sensitized, three with a mean class I PRA of 16% and two with a mean class II PRA of 37%. In conclusion, patient and graft survivals were excellent, mean Treg percentage was not elevated with results lower than in the early posttransplant period. Rejection incidence was negligible. Late "de novo" sensitization occurred in 70% showing that B cell-mediated alloresponses were only partially controlled among recipients induced with C1H even when associated with sustained anticalcineurin treatment.

Quality control of the total lymphocyte count parameter obtained from routine haematology analyzers, and its relevance in HIV management.

Lylmphocyte subsets/CD4 T Helper cell enumeration in HIV care and treatment in resource constrained settings can be difficult to ascertain as a result of the lack of the necessary instrumentation, capacity and infrastructure. However. it is imperative to gain such information for patient monitoring in HIV. The Total Lymphocyte Count (TLC) is useful as a surrogate marker for CD4 count as recommended by the World Health Organisation (WHO) and to calculate CD4% for pacdiatric use. This study therefore sets out to determine and compare the accuracy of the total lymphocyte counts obtained from three haematology analysers designated A. B and C. that are in regular use for routine haemnatological parameters at the main referral hospital in Barbados. West Indies. The TLC of 263 HIV treatment naive individuals attending the HIV Reference Unit in Barbados were enumnerated on the three haematology analysers. The lymphosumn (Sum of lymphocyte subsets: T-helper cell. T-cytotoxic cells. B lymphocytes and Natural killer cells) should be equal to the TLC. and is derived by immunophenotypic analysis on a 4-colour flowcytometer. Machine C had the highest positive correlation between the TLC and the lymphosumn with and R' of 0.9031 compared to machine A with an R values of 0.7119 and Machine B with R(2) values of 0.637. These results show that there can be dramatic inaccuracies when using routine haematology analysers for both routine use. as a surrogate marker of CD4 or for derivation of CD4% in HIV management. It further demonstrates that all haematology analyzers require some form of Quality control. The possible lack of accuracy of the TLC by haematology analysers should be taken into consideration when following the recommendations of the WHO in resource poor settings or using it as a denominator for calculating CD4%.

Seroprevalence of antibodies against varicella-zoster virus and response to the varicella vaccine in pediatric renal transplant patients.

The severity of varicella-zoster virus (VZV) in immunocompromised children, especially in those receiving renal transplants, is well known. However, the use of live attenuated virus vaccine in this population is controversial. This study aimed to: (i) assess the immunization status of pediatric renal transplant recipients at our center; (ii) determine the anti-VZV antibody titers in such patients; (iii) evaluate the response to VZV vaccine in seronegative children and in those who present low antibody titers (defined as <500 mAU/mL). Vaccinated children were monitored for adverse effects for 8 wk after vaccination. Fifty patients with a mean age of 13.7 yr (range, 3-17 yr) were enrolled. In 49, blood samples were collected and antibodies were screened using ELISA. Seropositivity to VZV was found in 43 (88%), and antibody titers were >/=500 mAU/mL in 37 (75.5%). Of the 12 children who were eligible for vaccination and had antibody titers <500 mAU/mL, one developed varicella before vaccination, two did not meet the inclusion criteria, and three parents refused the vaccination. In the six vaccinated children, there were no adverse reactions to the vaccine, and four (66.6%) responded with anti-VZV titers >/=500 mAU/mL 6-8 wk after vaccination. In conclusion, after renal transplantation, varicella vaccine is safe with a 66% rate of conversion to high antibody titers.

CD25+CD4+ regulatory T cells in patients with Kawasaki disease.

OBJECTIVE: To investigate whether the CD25 + CD4 + regulatory T-cell population, which plays important roles not only in maintaining immunologic self-tolerance but also in controlling the magnitude and character of antimicrobial immune responses, is related to the pathophysiology of Kawasaki disease (KD). STUDY DESIGN: The patient group consisted of 54 patients (median age, 30 months; 27 female and 27 male patients) fulfilling the criteria for KD. Age-matched control subjects included 17 patients with active infections and 24 healthy children. We analyzed CD25 + CD4 + cells and the mRNA expression of Foxp3, cytotoxic T lymphocyte-associated antigen 4 (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), and transforming growth factor beta in peripheral blood mononuclear cells and purified CD4 + T cells. RESULTS: The proportions of CD25 + CD4 + cells in patients with acute-phase KD (median, 2.35% of total lymphocytes) were significantly lower than those in healthy control subjects (median, 3.14%) and control subjects with disease (median, 3.15%). The proportions returned to the normal level after intravenous gammaglobulin treatment (median, 3.86%). The mRNA expression of Foxp3, CTLA4, and GITR showed similar tendencies. CONCLUSIONS: The decrease of CD25 + CD4 + regulatory T cells in the acute phase might have a role in the development of KD.

A consistent pattern of minor immunodeficiency and subtle enteropathy in children with multiple food allergy.

OBJECTIVE: Although immunoglobulin (Ig)E-mediated allergies are readily identifiable, non-IgE-mediated allergies present more diagnostic difficulty. We performed a formal retrospective analysis to determine whether there is a recognizable clinical pattern in children. METHODS: We studied 121 children (mean age, 17.3 months) with multiple food allergies who were recruited on the basis of adequate immunological assessment by using case notes and parental questionnaire. RESULTS: Group 1 (n=44) had rapid reactions to dietary antigens, of whom 41 also showed delayed reactions. Group 2 (n=77) had delayed reactions only. Mean IgE was increased in group 1 but both groups otherwise shared a pattern of increased IgG1, decreased IgG2/4, and low-normal IgA. Lymphocyte subsets were skewed, with an increased percentage of CD4 and CD19 and decreased CD8 and natural killer cells. Gastroesophageal reflux, esophagitis, subtle enteropathy, and constipation were frequent in both groups. Of 55 exclusively breast-fed infants, 44 sensitized before weaning. Twenty-one of the mothers suffered from autoimmunity. CONCLUSIONS: There appears to be a recognizable pattern of immune deviation and minor enteropathy in children with multiple food allergy, irrespective of the speed of reactions. Disturbed gut motility is particularly common, as is a maternal history of autoimmunity.

Effect of in vivo administered hexachlorobenzene on epidermal growth factor receptor levels, protein tyrosine kinase activity, and phosphotyrosine content in rat liver.

In the present study, the effects of hexachlorobenzene (HCB) on epidermal growth factor receptor (EGFR) content of liver microsomes and plasma membrane, and on EGFR-tyrosine kinase activity in the microsomal fraction were investigated. In addition, we studied the parameters of the tyrosine kinase signalling pathway such as protein tyrosine kinase (PTK) activity and phosphotyrosine content in microsomal and cytosolic protein. To determine whether the observed alterations were correlated with a manifestation of overt toxicity, a single very low dose of HCB (1mg/kg body wt) and two much higher doses (100 and 1000 mg/kg body wt), the highest being toxicologically significant in that it reduced serum thyroxine (T(4)) and inhibited uroporphyrinogen decarboxylase (URO-D) (EC 4.1.1.37) activity, were tested. Our results demonstrated that liver microsomes of rats treated with HCB had higher levels of EGFR than untreated rats; treated rats also had less EGFR present in hepatocyte plasma membrane fractions than did untreated rats. HCB altered the phosphotyrosine content and protein phosphorylation of some microsomal and cytosolic proteins in a biphasic dose-response relationship. At the low dose, phosphorylation and phosphotyrosine content of several microsomal proteins were increased; however, these effects were diminished or reversed at the higher doses. Our results suggest that chronic HCB treatment produces a down-regulation of the EGFR and a dose-dependent increase in EGFR-tyrosine kinase activity in the microsomal fraction. This effect may contribute to the alteration of membrane and cytosolic protein tyrosine phosphorylation. The level of sensitivity encountered in our studies is extraordinary, occurring at 1/10 to 1/1000 the doses of HCB known to cause other toxicological lesions.

Patterns of cytokines and soluble cellular receptors in the sera of children with acute chagas' disease.

Cytokines and soluble cellular receptors are involved in inflammatory processes and probably in the pathogenesis of parasite and bacterial diseases. In a previous study, we reported increased levels of soluble receptors of interleukin-2 (sIL2-R) in children with acute Chagas' disease, one of the main parasitic infections that is endemic in Latin America. We sought to analyze the pattern of different cytokines and soluble receptors in the sera of children with chagasic infection. Children with acute and indeterminate stages of Chagas' disease, as well as nonchagasic children, were studied. Sera were assayed by enzyme-linked immunosorbent assay to measure the levels of tumor necrosis factor alpha (TNF-alpha), IL-6, IL-2, IL-8, IL-12, sIL-2R, and the soluble receptors of CD8 and CD4 (sCD8 and sCD4). sIL-2R and sCD8 showed the highest levels in serum in acutely infected children, decreasing after specific antiparasite therapy. Chronic children showed a pattern similar to the one of nonchagasic children. Although they were not statistically significant, TNF-alpha, IL-6, and sCD4 showed a tendency to reach high levels in the acutely infected group, whereas IL-2, IL-8, and IL-12 did not reveal changes with respect to the noninfected children. In summary, we report here the patterns of cytokines and soluble receptors in in the sera of children infected with Trypanosoma cruzi; we found significantly increased levels of sIL-2R and sCD8 in acute infection that decreased after therapy, and high levels of TNF-alpha, IL-6, and sCD4 in some of the acute patients. The measurement of sIL-2R and sCD8 may provide a useful tool in the follow-up of children with Chagas' disease.

[Immune events in central nervous system of early and late onset Alzheimer's disease patients]. / Eventos inmunológicos en el sistema nervioso central de pacientes con enfermedad de Alzheimer temprana y tardía.

INTRODUCTION: Alzheimer s disease (AD) is a progressive degenerative disease affecting a significant proportion of the elderly population. The disease is characterized clinically by a progressive loss of memory function and mental impairment associated with the presence of degenerative well known pathological lesions. Although, the pathogenesis of AD is unclear; several reports indicate the involvement of immune factors. PATIENTS AND METHODS: This paper evaluates some cerebrospinal fluid immune markers from 21 patients with early and late AD and 20 age matched non-demented subjects. The analytical method included the evaluation of T cell subpopulations (using AcMc CD2, CD4, CD8) and activated T cells (AcMc HLA-DR and CD25) from CSF and peripheral blood by immunocytochemical techniques on a fixed cell slide as described by Bernd. The lymphocyte phenotype expressed as a percentage of positively stained cells for each cell surface marker evaluated. RESULTS: Some significant differences were observed for T cell subpopulations from different compartments, between the different AD groups and the controls (p< 0.05). Nevertheless, the most significant differences were found in the activated T cells from cerebrospinal fluid between AD groups and controls (p< 0.01). CONCLUSIONS: These results support the theory of neuroimmune dysregulation, probably involved in the progressive neurodegeneration and dementia in some AD.

Doppler echocardiographic evaluation of HIV-positive patients in different stages of the disease.

OBJECTIVE: To evaluate by Doppler echocardiography (DE) early abnormalities of ventricular function in HIV-positive patients, as well as other cardiac abnormalities that can be detected by this method, with special emphasis on mitral valve flow. METHODS: 84 HIV-positive patients, 59 with CD4 cell count > 500/mm3 (Group A) and 25 with CD4 cell count < 500/mm3 (Group B), were analyzed. CD4 cells were counted and matched with structural data and systolic and diastolic function of the left ventricle (LV), as analyzed by DE. The results were compared with those obtained in 47 healthy individuals (Group C). RESULTS: 8% of patients in Group B had mild pericardial effusion; 31.5% showed decreased systolic function of the LV, and 12% had moderate mitral regurgitation. A wave velocity from the mitral inflow was different among the 3 groups, being higher in Group B, where the deceleration time of the E wave of the mitral inflow and the E/A ratio were significantly lower with a normal value of the isovolumic relaxation time (IVRT). CONCLUSION: HIV-positive patients with a CD4 cell count > 500/mm3 had no abnormalities by DE. Patients with a more advanced infection (those with a CD4 cell count < 500/mm3), had a significantly abnormal LV systolic function and a higher incidence of pericardial effusion and mitral regurgitation. Mitral valve inflow by Doppler did not indicate diastolic dysfunction.

Increased CD4-positive monocytes in HIV-infected haemophilic patients.

The monocyte-macrophage system is known to play a central role in HIV infection, and expression of CD4 on the surface of monocytes/macrophages is important, since this molecule is a key factor for the entrance of HIV into susceptible cells. In this paper we evaluated the expression of CD4 in monocytes of haemophilic patients (He) who had been infected with HIV (HIV + He) through transfusion of contaminated plasma concentrates. Thirty seropositive patients (HIV + He), 10 seronegative He patients (HIV-He) and 20 voluntary normal blood donors were studied. Phenotypic evaluation of monocytes was performed by flow cytometry of peripheral blood stained with anti-CD45, -CD3, -CD4 and -CD14 monoclonal antibodies. The percentage of CD4 monocytes was increased in all HIV+ patients groups, but it was highest in those belonging to Groups III and IV A of the CDC classification. Furthermore, the median of fluorescence intensity of CD4+ monocytes from individual patients was shifted to the right, indicating expression of increased numbers of CD4 molecules on the cell membrane of monocytes. This could in turn favour HIV infection and viral persistence, facilitating in vivo dissemination of the virus.

Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis.

Visceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery from VL is linked to cellular immune response. Unresponsiveness to antimonial therapy reinforces the importance of determining parameters for treatment assessment. We analysed the pre- and post-treatment serum levels of soluble CD4 (sCD4), sCD8, sIL-2R, soluble intercellular adhesion molecule-1 (sICAM-1) and neopterin in groups of VL patients either responsive or not to standard antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1 were significantly higher in VL patients than in healthy subjects from the same area (P < 0.05). sICAM-1 levels were similar in healthy controls and in VL patients refractory to antimonial therapy (P = 0.25), but significantly higher in patients responsive to treatment (P = 0.02). The comparison of pre- and post-treatment concentrations showed that all markers, except sCD4 and sICAM-1, presented a significant fall (P < 0.05) in patients responsive to antimonial therapy. However, only neopterin presented with levels compatible with those of healthy subjects at the end of treatment (P = 0.30). In refractory patients sICAM-1 presented with post-treatment levels significantly higher than the pretreatment determinations (P = 0.03), while sCD4 experienced a significant drop (P = 0.01). All markers displayed clearly distinct behaviour according to the patient's response to therapy. This makes all soluble molecules studied suitable for use as indicators of antimonial therapy response. Additionally the comparison of pretreatment levels of the markers between responders and refractory patients to antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1 significantly differed among these two groups (P = 0.02 in each case), suggesting that they may be used in future as predictors of antimonial therapy response.

The first report of familial adult T-cell leukaemia lymphoma in the United Kingdom.

We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older sibling had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents the development of ATLL in second-generation Caribbean immigrants.

The first report of familial adult T-cell leukaemia lymphoma in the United Kingdom

We describe two siblings who developed adult T-cell leukaemia lymphoma (ATLL) within 4 years. Both were black of Afro-Caribbean extraction, but one had been born in the United Kingdom and had visited the Caribbean only once. Both patients were HTLV-1 seropositive, as was their mother; their father and brother were negative. The older siblings had the lymphoma form of ATLL, whilst the younger had chronic ATLL. The former was unresponsive to chemotherapy and died of progressive disease; the latter chemotherapy and died of progressive disease; the latter experienced transient responses to various treatments and is alive 5 years after presentation. Immunophenotyping showed a CD4+, CD25+ phenotype; Southern blot demonstrated a monoclonal integration of HTLV-I in the tissues involved. This report, of the first familial ATLL in the U.K., supports the suggestion of transmission of HTLV-I from mother to child and documents and the development of ATLL in second-generation Caribbean immigrants (AU)

Evolución inmunológica de madres HIV reactivas y sus hijos / Immunology evolution of mother reactive HIV and sons

De 23 partos de madres HIV reactivas, ingresaron en el estudio 17 de ellas y 22 niños, confirmados por 2 ELISA, IFI (inmunofluorescencia indirecta) y Western blot. El propósito fue controlar cada tres meses su inmunidad celular (IMC) y humoral por medio de test de rosetas, subpoblaciones linfocitarias CD3, CD4, CD8, relación CD4/CD8 para linfocitos T, DR para linfocitos B, CMI multitest para linfocitos T con memoria. Proteinograma electroforético, inmunoglobulinas séricas (IgG, IgM e IgA), C3 y C4 por inmunodifusión radial. Del total de madres, 10 (58,8 por ciento) presentaron una relación CD4/CD8<1, la mitad de ellas un recuento CD4<400/mm3 (252, 252, 359, 279, 194/mm3). Valores tan bajos como este último se detectaron en forma previa a la muerte de una de ellas. De este grupo, cuatro presentaron hipergammaglobulinemia y elevación de IgG con sintomatología clínica, a diferencia del resto de madres con déficit de IMC pero con valores de CD4 por encima de 400/mm3; durante los controles seriados, en tres de ellas se produjo un segundo embarazo en cuyo curso se observó una disminución de la IMC. En cuanto a los niños, nueve se tornaron negativos después de los seis meses de vida; de los trece que continúan siendo seropositivos, dos presentaron un déficit de IMC, con disminución progresiva de CD4 (4 085; 3 401; 2 008; 1 445/mm3), (662; 491; 1 519/mm3) y de relación CD4/CD8 (1,88; 0,99; 0,58; 0,82), (0,69; 0,31; 0,30). No se observaron valores tan bajos de CD4 como en los adultos, pero sí un descenso del 50 por ciento del valor inicial en un niño durante su primer año de vida. Estos niños corresponden al grupo de madres con CD4<400/mm3. Los resultados sugieren que la negativización se produce después de los seis meses de vida. El déficit de IMC, sobre todo una relación CD4/CD8<1, CD4<400mm3, hipergammaglobulinemia y elevación de IgG son de mal pronóstico. Las madres con severo compromiso inmunitario presentan mayor riesgo de infectar intraútero. Durante el curso de su embarazo presentaron una disminución de IMC. El chequeo seriado de inmunidad permite detectar actividad del virus en infectados y su evolución a enfermedad antes de que se presente sintomatología clínica

Placental involvement in paracoccidioidomycosis.

A case of juvenile-type paracoccidioidomycosis in a pregnant woman is reported. The disease pre-dated pregnancy and antifungal treatment was being administered when she became pregnant. A premature male infant was delivered with no evidence of infection. Microscopic examination of the placenta showed numerous Paracoccidioides brasiliensis yeast forms in the intervillous space, enmeshed in a macrophagic-phagocytic reaction, with damage of the trophoblastic layer. Placental transfer of specific P. brasiliensis antibodies was demonstrated.