Cristina Miuki Abe Jacob

Autoimmunity in IgA deficiency: revisiting the role of IgA as a silent housekeeper.

Both systemic and organ-specific autoimmune diseases are major manifestations of IgA deficiency (IgAD), the most common primary immunodeficiency. In addition, to discuss the clinical findings of IgAD patients, we proposed a hypothesis to explain the high association with autoimmune phenomena. Based on observations, interactions of monomeric IgA with FcαRI result in a partial phosphorylation of FcRγ-associated FcαRI, notably in the immunoreceptor tyrosine-based activation motif (ITAM) inducing the recruitment of the SHP-1 tyrosine phosphatase. This leads to deactivation of several activating pathways of the immune system including immunoreceptors that bear ITAM motif and ITAM-independent receptors. Consequently, inflammatory reactions and auto-immune process would be prevented.

Freqüência de soropositividade para antígenos de Toxocara canis em crianças de classes sociais diferentes

Frequency of seropositivity for Toxocara in children from different socioeconomic strata in the city of Brasilia (Brazil) was measured. Six hundred and two children of both sexes, aged one to 12 years were distributed in two socioeconomically distinct groups. The samples of sera of the first group were obtained from blood drawn for routine tests in the laboratory of a public hospital attending children from low-income families. Samples from the second group were obtained from private laboratories attending children from middle-class families. Anti-toxocara antibodies were detected by ELISA, using Toxocara canis excretory-secretory antigens previously absorbed with Ascaris suum extract. The prevalence of seropositivity was 21.8% (66/302) in the first group and 3% (9/300) in the second (p< 0.0001). No differences in frequency according to age or sex could be detected. Our results suggest a high prevalence of childhood toxocariasis in Brasilia, with children from lower income brackets being the most affected.

Visceral leishmaniasis: clinical and laboratorial aspects

OBJECTIVE To compare the clinical and laboratorial data before and after the treatment of patients with visceral leishmaniasis admitted to a pediatric hospital in a nonendemic area, highlighting the importance of recognizing visceral leishmaniasis in pediatric patients. METHODS Clinical, laboratorial and treatment data of 78 patients with visceral leishmaniasis were evaluated from 1981 to 1992. We analyzed the average level of hemoglobin, leukocyte, neutrophil, platelet, albumin, gammaglobulin, class and subclass of immunoglobulin, size of the liver and spleen during the pre- and post-treatment using the paired t test. RESULTS We included 78 patients with visceral leishmaniasis, 44 males, with age ranging from 8 months to 13.5 years. Sixty-one patients were from Bahia. Fever and splenomegaly were present in 96.1% and 100% of the cases, respectively. The parasitological diagnosis was obtained in 74/78 patients: 67 patients through smear and/or culture of bone marrow (85.7%), five through liver biopsy and two through spleen puncture. The hematological findings and serum albumin presented significant improvement at the end of treatment (P<0.001), differently from serum gammaglobulin levels (P=0.087). There was predominance of IgG1 subclass, with two patients presenting low levels of IgG2. Initial treatment used antimoniate in 67 cases and amphotericin B in five. Eleven patients (15.7%) needed a second treatment, and were considered cured after it. There was significant improvement in the liver and spleen size at the end of the treatment (P<0.001). One patient presented spontaneous remission and five died due to bleeding. CONCLUSIONS In order to obtain accurate diagnosis and treatment, especially regarding health services of areas with low-incidence of visceral leishmaniasis, the diagnosis of patients with fever and visceromegaly, who come from endemic areas, should include visceral leishmaniasis.

Brazilian report on primary immunodeficiencies in children : 166 cases studied over a follow-up time of 15 years

One hundred sixty-six cases of primary immunodeficiency diseases (PID) (95 males, 71 females), diagnosed according to WHO criteria, have been registered at the Childrens Hospital, University of São Paulo, Brazil. The following frequencies were found: predominantly humoral defects, 60.8% (n = 101); T cell defects, 4.9% (n = 8); combined ID, 9.6% (n = 16); phagocyte disorders, 18.7% (n = 31); and complement deficiencies, 6% (n = 10). IgA deficiency was the most frequent disorder (n = 60), followed by transient hypogammaglobulinemia (n = 14), chronic granulomatous disease (n = 14), and X-linked agammaglobulinemia (n = 9). In comparison to other (national) reports, we observed higher relative frequencies of phagocyte and complement deficiencies. Recurrent infections were the cause of death in 12.7%. Allergic symptoms were observed in 41%, mainly in IgA-deficient, hypogammaglobulinemic, or hyper-IgE patients, and autoimmune disorders in 5%, predominantly in IgA and complement deficiencies. Five patients suffered from BCG dissemination; two of them died. This is the first Brazilian report on PID over an observation time of 15 years.

The role of probiotics and prebiotics in pediatric practice.

OBJECTIVE To review the effects of probiotics and prebiotics in clinical pediatric practice. SOURCES MEDLINE was searched, especially for articles that addressed their practical application, in the form of reviews, clinical trials and meta-analyses. Articles that had already been analyzed by the authors were also included. SUMMARY OF THE FINDINGS Scientific literature on probiotics and prebiotics has remarkably increased in the last 10 years. Their mechanisms of action have been experimentally investigated. Studies indicate that probiotics can act by competing with pathogens, modifying the intestinal environment by reduction in pH, as a result of fermentation products, interacting and modulating local and systemic inflammatory and immune response, among others. Clinical trials and meta-analyses show that probiotics seem to contribute towards the prevention of acute diarrhea and of antibiotic-associated diarrhea, in addition to shortening the duration of acute diarrhea. However, the data are inconsistent and there are no studies confirming their efficacy in terms of cost-benefit ratio. Preliminary studies show that probiotics in early life can reduce the occurrence of atopic dermatitis. The addition of prebiotics to infant formulas is associated with the change in the profile of the intestinal microbiota compared to infants fed milk formulas without prebiotics. CONCLUSIONS Evidence indicates that new studies should be carried out about probiotics, prebiotics and symbiotics. The specific clinical effects that each probiotic or prebiotic may cause must be considered.

Clinical and laboratorial features of visceral toxocariasis in infancy

Forty children with a diagnosis of Visceral Toxocariasis were evaluated prospectively from February 1982 to June 1989. Diagnosis was established by clinical, laboratory and serological (ELISA - ES Toxocara canis antigen) evaluations. A great clinical polymorphism was found in our patients, ranging from unspecific or absent manifestations to an exuberant symptomatology. The laboratory findings were: leukocytosis, eosinophilia and elevation of serum gammaglobulin and isohemagglutinin levels. No significant relationship between clinical findings and laboratory parameters was found. Serology (ELISA) was a method of great diagnostic support but did not show a correlation with clinical and laboratory findings in this study. There was a significant relationship between pulmonary manifestations and the presence of signs and/or symptoms, when the patients were sent to us. Our findings, especially the high incidence of pulmonary manifestations, suggest that Visceral Toxocariasis has to be included in the differential diagnostic of children with pulmonary manifestations, characteristic epidemiological data and associated eosinophilia.

Griscelli Syndrome: Characterization of a New Mutation and Rescue of T-Cytotoxic Activity by Retroviral Transfer of RAB27A Gene

Griscelli syndrome (GS) is caused by mutations in the MYO5A (GS1), RAB27A (GS2), or MLPH (GS3) genes, all of which lead to a similar pigmentary dilution. In addition, GS1 patients show primary neurological impairment, whereas GS2 patients present immunodeficiency and periods of lymphocyte proliferation and activation, leading to their infiltration in many organs, such as the nervous system, causing secondary neurological damage. We report the diagnosis of GS2 in a 4-year-old child with haemophagocytic syndrome, immunodeficiency, and secondary neurological disorders. Typical melanosome accumulation was found in skin melanocytes and pigment clumps were observed in hair shafts. Two heterozygous mutant alleles of the RAB27A gene were found, a C-T transition (C352T) that leads to Q118stop and a G-C transversion on the exon 5 splicing donor site (G467+1C). Functional assays showed increased cellular activation and decreased cytotoxic activity of NK and CD8+ T cells, associated with defective lytic granules release. Myosin-Va expression and localization in the patient lymphocytes were also analyzed. Most importantly, we show that cytotoxic activity of the patients CD8+ T lymphocytes can be rescued in vitro by RAB27A gene transfer mediated by a recombinant retroviral vector, a first step towards a potential treatment of the acute phase of GS2 by RAB27A transduced lymphocytes.

Clinical and laboratory aspects of chronic granulomatous disease in description of eighteen patients

To describe the epidemiological, clinical, laboratory, and evolution characteristics of 18 patients with chronic granulomatous disease (CGD). In this retrospective study, clinical, laboratory, and epidemiological data were obtained from the medical records of all patients with CGD seen at the Allergy and Immunology Unit of the Pediatrics Department (School of Medicine, University of Sao Paulo) from January 1979 to December 2001. Medical history and physical examination data, personal and family history, presence of consanguinity, weight and height data, presence of hepatosplenomegaly, adenomegaly, or other relevant alterations at the time of admission were obtained for all patients. We reviewed 18 patients (male:female, 8:1) with a median duration of symptoms of 1.25 months and with a median time since diagnosis of 13 months. A family history of death as a result of infection was reported by three patients and five other patients had a common relative with CGD who was included in the series. The clinical manifestations observed were: failure to thrive, adenomegaly, hepatosplenomegaly, pneumonia, and abscesses. Relevant laboratory data were hypergammaglobulinemia and nitroblue tetrazolium reduction test of 0% in 14 patients. Seven patients received IFN‐γ and 11 sulfamethoxazole–trimethoprim. Six patients died of suppurative pulmonary infections. Age at the onset of symptoms was early, although diagnosis was late in some patients. Pulmonary involvement was the most prevalent clinical manifestation in the different phases of the disease and the major cause of death. Hypergammaglobulinemia, anemia, and leukocytosis were relevant laboratory data.

Sensitisation to aeroallergens in Brazilian adolescents living at the periphery of large subtropical urban centres

OBJECTIVES To evaluate the sensitization to aeroallergens determined by skin prick test (SPT) in Brazilian adolescents, and to correlate its positivity with the diagnosis of asthma and/or rhinitis based on the written questionnaire (WQ) of ISAAC phase III study. PATIENTS AND METHODS A total of 996 adolescents (387 boys) were selected by systematic samples. A standard allergen extracts panel (positive/negative control, D pteronyssinus [Dpt], P americana [Pa], B germanica [Bg], dog, cat, fungal and grass mix) was used and its positivity compared with positive responses to asthma, rhinitis or both. RESULTS Positive SPT to at least one allergen was observed in 466 adolescents (46.8 %), with sensitisation to Dpt in 79.1 %. Positivity to more than one allergen occurred in 232 students (49.8 %). The frequency of positive SPTs was significantly higher among adolescents with asthma (OR = 2.16), rhinitis (OR = 1.69), and asthma and rhinitis (OR = 2.03). Positive SPT to four or more allergens were higher among asthmatics (OR = 2.6) and among adolescents with asthma and rhinitis (OR = 3). CONCLUSIONS A high sensitisation rate to aeroallergens was observed, significantly higher among those with asthma, rhinitis or a combination of both, especially in multiple sensitisations.

Assessment of muscle shortening and static posture in children with persistent asthma

Asthmatic patients experience an increase in airway resistance that overburdens both respiratory and non-respiratory muscles. The objective of the present study was to determine whether children with persistent asthma present muscle shortening and postural changes. The 60 boys evaluated, aged 7–12 (pubertal ages up to Tanner stage G2) were divided into three age- and BMI-matched groups of equal number: CON (no history of asthma or allergy); MPA (mild persistent asthma); SPA (severe persistent asthma). Pulmonary function, muscle shortening and static posture were evaluated. The SPA group presented higher protraction of the head and shoulder compared with the CON group [9.5 (6.0–12.0) degrees vs 5.5 (0.0–12.0) degrees, P < 0.05; 0.89 (0.80–0.94) anterior/posterior ratio vs 0.94 (0.87–1.1) anterior/posterior ratio, P < 0.01)]. Severe asthmatic patients also presented shortening of arm flexor and posterior muscle of the thigh compared with the CON group [18.0 (10.0–24.0) degrees vs 12.0 (6.0–16.0) degrees, P < 0.05; and 16.5 (10.0–38.5) cm vs 8.0 (0.0–21.0) cm, respectively, P < 0.05]. Chest expansion at axillar and xiphoid levels were limited in SPA subjects compared with CON subjects [3.7 (1.5–6.5) cm vs 5.5 (2.0–8.0) cm and 4.7 (1.5–6.5) vs 6.0 (3.5–8.0) cm, respectively, P < 0.01]. SPA subjects also presented a higher incidence of lumbar spine straightening compared with CON and MPA subjects. Moderate asthmatic subjects presented intermediate values compared with severe and control subjects in five out nine evaluated outcomes. Our data suggest that severe asthmatic children present postural adaptations and muscle shortening that seem to be related to disease severity.