CD40 Ligand Deficiency.

CD40 ligand deficiency (CD40L), currently classified as an inborn error of immunity affecting cellular and humoral immunity, prevalently emerges in boys within the first two years of life. It manifests itself as a decrease in serum IgG, IgA and IgE, with normal or high IgM, defects in T cell proliferation, and decrease in soluble CD40L. These accompany sinopulmonary and/or gastrointestinal infections, and there may be infections caused by pyogenic bacteria, opportunistic infections, autoimmune diseases, and neoplasms. Mild and moderate cases of this deficiency may respond well to prophylactic antibiotic therapy or to human immunoglobulin replacement therapy, in addition to the early treatment of infections. Severe cases can be treated with hematopoietic stem cell transplantation, which allows the healing of such patients, rather than sequelae and a poor progression. Thus, its differential diagnosis with other inborn errors of immunity is essential, especially CD40 deficiency and variable common immunodeficiency; the reason why we have proposed the present literature review.

A prospective ten-year follow-up of patients with chronic urticaria.

BACKGROUND: Chronic urticaria can be the initial clinical presentation of a number of different diseases. The objective of the present study was to report the associated diseases during a ten-year clinical-laboratory follow-up in patients with an initial diagnosis of chronic spontaneous urticaria (CSU) of unknown cause. METHODS: A prospective, longitudinal cohort study with a ten-year clinical-laboratory follow-up was conducted. Patients with a history of urticarial plaques of over six weeks presenting as the only clinical symptom were selected. Individuals with other clinical conditions, urticaria of known causes or chronic physical urticaria were excluded. The following tests were initially performed: haemogram, urine type I, stool parasite exam and sedimentation rate. The following exams were ordered during follow-up: PPD; urine culture; serology tests; antithyroid and antinuclear antibodies, rheumatoid factor, lupus anticoagulant; thyroid hormones; serum immunoglobulin; paranasal sinus and thorax radiographs; testing for BK and Helicobacter pylori; and prick tests. RESULTS: Infections were diagnosed in 29% of patients (syphilis, parasitosis, H. pylori, urinary infection, tuberculosis, hepatitis B and C); autoimmune diseases in 21% (thyroiditis, rheumatoid arthritis and antiphospholipid antibody syndrome); primary immunodeficiencies in 4% (IgA and IgG2 deficiencies); and chronic myeloid leukaemia in 1%. At ten-years of follow-up, the urticaria diagnosis was CSU of unknown cause in 45% of the cases. CONCLUSION: This ten-year clinical-laboratory follow-up of 100 individuals with chronic urticaria as the initial diagnosis revealed the presence of associated diseases in over half of the cases. The most prevalent diseases were infections and autoimmune diseases besides primary immunodeficiencies and blood diseases.

Evaluation of neutrophilic activity in patients submitted to kidney transplantation.

BACKGROUND: Cryoglobulinemia is frequent in renal transplant patients. The mononuclear and polymorphonuclear neutrophil (PMN) phagocytic systems are important for the clearance of cryoglobulin immune complexes. There might be a reduced phagocytic activity in transplant patients with cryoglobulinemia (CRYO+). METHODS: We studied the phagocytic activity by PMNs, in the presence of immune complexes in renal transplant patients, with or without hepatitis C virus (HCV) infection. Thirty-seven patients subjected to kidney transplant were evaluated, and for the control group, healthy blood donors were chosen. The presence of cryoprecipitate was evaluated, as well as HCV infection, phagocytic activity by neutrophils during the ingestion and digestion phase. RESULTS: The presence of cryoprecipitate was detected in 75.7% of the patients, 39.28% of which had HCV infection. IgG, IgM, IgA, and C3 and C4 complement components were identified in the cryoprecipitate. There was a reduction in the ingestion phase of phagocytosis by PMNs in renal transplant CRYO+ though the digestion phase was preserved. CONCLUSION: We concluded that there was a decreased PMN activity in transplanted patients presenting cryoglobulinemia.

Evaluation of phagocytes in atopic dermatitis

Background: Patients with atopic dermatitis frequently present recurrent infections by pyogenic bacteria or by intracellular microorganisms, suggesting an immune disorder. Objective: Laboratorial investigation of phagocyte activity and chemotactic response by neutrophilic polymorphonuclear and mononuclear phagocytes in the peripheral blood of patients with atopic dermatitis from moderate to severe. Methods: Through a transversal study, patients with atopic dermatitis from moderate to severe were selected. The neutrophilic and mononuclear phagocytes were separated and the phagocytic ingestion of zymosan particles was analysed, in addition to migration distance to the bacterial lipopolysaccharide chemotactic factor, comparing the results to the values obtained from healthy individuals within the same age group. Results: Nineteen patients were selected, 11 female and 8 male. The mean age was 6.47 years (±4.65). Among the 19 patients studied, 14 (73.68%) presented a reduction in the neutrophilic and mononuclear phagocyte activity, with two (1.53%) patients presenting a reduction in the activity of both phagocytes. Conclusion: Our results demonstrated a reduction in chemotactic response and phagocytic activity by neutrophilic and/or mononuclear phagocytes in the majority of patients with atopic dermatitis from moderate to severe. Our results were coherent with the clinical data concerning the higher incidence of infections by pyogenic bacteria and fungi in patients with atopic dermatitis, which are microorganisms that require defence by the phagocytes researched in the present study (AU)

Evaluation of phagocytes in atopic dermatitis.

BACKGROUND: Patients with atopic dermatitis frequently present recurrent infections by pyogenic bacteria or by intracellular microorganisms, suggesting an immune disorder. OBJECTIVE: Laboratorial investigation of phagocyte activity and chemotactic response by neutrophilic polymorphonuclear and mononuclear phagocytes in the peripheral blood of patients with atopic dermatitis from moderate to severe. METHODS: Through a transversal study, patients with atopic dermatitis from moderate to severe were selected. The neutrophilic and mononuclear phagocytes were separated and the phagocytic ingestion of zymosan particles was analysed, in addition to migration distance to the bacterial lipopolysaccharide chemotactic factor, comparing the results to the values obtained from healthy individuals within the same age group. RESULTS: Nineteen patients were selected, 11 female and 8 male. The mean age was 6.47 years (+/-4.65). Among the 19 patients studied, 14 (73.68%) presented a reduction in the neutrophilic and mononuclear phagocyte activity, with two (1.53%) patients presenting a reduction in the activity of both phagocytes. CONCLUSION: Our results demonstrated a reduction in chemotactic response and phagocytic activity by neutrophilic and/or mononuclear phagocytes in the majority of patients with atopic dermatitis from moderate to severe. Our results were coherent with the clinical data concerning the higher incidence of infections by pyogenic bacteria and fungi in patients with atopic dermatitis, which are microorganisms that require defence by the phagocytes researched in the present study.

Immune function in acute stress.

UNLABELLED: The aim of this study was to evaluate immune function in acute stress in medical students before academic examinations. Twenty-five medical students were selected because they presented intense acute stress, evaluated by the presence of the following classic signs: cold hands, intense sudoresis in the extremities, generalized sudoresis, paleness, tachycardia, confused reasoning, nervous irritability, diarrhea, and sleep disorders in the hours preceding the examination (agitated sleep, insomnia). METHODS: Immediately before the examination, peripheral blood was collected from the 25 students presenting acute stress to analyze T and B cells, CD4+ and CD8+ cells, immunoglobulins, and C3 and C4 complement components, as well as phagocytic activity in neutrophils and monocytes. These investigations were repeated in the same students in situations free of acute stress. The results of the two samples collected from each student were compared. RESULTS: The means and standard deviations showed no significant differences for any of the parameters analyzed (p> or =0.01). CONCLUSION: We conclude that acute stress did not cause changes in the lymphocyte subpopulations, phagocytic activity of neutrophils and monocytes, serum immunoglobulins, or C3 and C4 complement components in students participating in the present study. In conditions of basal chronic stress, acute stress may cause alterations in immune function.

Rebound phenomenon to systemic corticosteroid in atopic dermatitis.

Three patients with atopic dermatitis, one boy and two girls, aged between 6 and 17 years, presented eczematous skin, pruritus, scarifications, lichenification and a family history of atopy. During exacerbations, the patients sought emergency care and were prescribed oral corticosteroids for a period of approximately 15 days. Initially, the patients improved but after cessation of therapy or dose reduction, marked worsening occurred with the development of lesions with extreme pruritus, several confluent lesions, scarification and intense exudates, as well as fever and dehydration. The patients' condition was so severe that two were admitted to the allergy unit. The medication was withdrawn and intravenous hydration was administered, together with hydrating skin creams and antihistamine therapy. In addition, weak topical corticosteroids were applied on the most severely affected areas. All three patients progressively improved. We conclude that the patients with atopic dermatitis described herein presented a rebound phenomenon after the use of corticosteroids. We believe that systemic corticosteroids may exacerbate the acute phase of atopic dermatitis, mediated by IgE, accentuating the Th2 pattern in these patients.

Different clinical and laboratory evolutions in ataxia-telangiectasia syndrome: report of four cases.

We report four patients with ataxia-telangiectasia syndrome that presented varied neurologic evolution. Three patients initially presented neurologic alterations of slow progression, evolving to late immunocompromised conditions. The fourth patient presented, from symptom onset, immune and neurologic debilitation, that were both severe and of fast progression. The chronological sequence of the most commonly observed immunocompromised conditions were in our patients, in ascending order, IgA deficiency, IgG2 deficiency and the neutrophil phagocytosis stage and common variable immunodeficiency. The first two reports are of sisters in whom the diagnosis was done between the ages of three and six years, having ocular apraxia, cerebellar ataxia and telangiectasia. Slow progression of neurologic debilitation was observed, without presentation of intermittent infections. The patients began presenting accentuated immunocompromised conditions at the ages of 14 and 17 years, dying at the ages of 16 and 20 years, respectively, due to severe infections that were resistant to treatment. The diagnosis of the third case was established when the patient was two years old, presenting ataxia and telangiectasia. Syndrome progression was slow, presenting at the age of eight years more accentuated neurologic disorders and IgA deficiency. The fourth case presented significant neurologic compromise at the age of five, simultaneous to IgA and IgG2 deficiency, and repeating pneumonias and sinusitis. At this time, intravenous gammaglobulin reposition was done. The neurologic and immune disorders progressed rapidly, and at the age of eight presented the inability to walk. At this time inversion of the CD4/CD8 ration was verified through laboratory tests.

Cryoglobulinemia in kidney transplant recipients.

The aim of this study was to assess the presence of cryoglobulins, the constitution of the cryoprecipitate, as well as the possible etiology and clinical features in kidney transplant recipients. We excluded patients with clinical or laboratory evidence of autoimmune, liver or neoplasm disease, infections, blood transfusions or immunizations in the previous 3 months. Detection of cryoglobulins was obtained from the peripheral venous blood. In cases of cryoprecipitate formation it was analyzed using anti-IgG, anti-IgM, anti-IgA, anti-C3, and anti-C4 antibodies. The hepatitis C virus (HCV) was detected by the polymerase chain reaction. Thirty-nine patients were selected, of whom 23 were men and the overall mean age was 40.6 +/- 12.7 years. Cryoprecipitate was detected in 74.4% (29/39) patients. Among patients with or without cryoprecipitate formation, the serum creatinine values, the percentage of patients with proteinuria, and the posttransplantation times were similar. In patients with cryoglobulins, 37.9% (11/29) were HCV positive. The etiology was not determined for the other patients. The IgG, IgM, and IgA immunoglobulins and the complement fractions C3 and C4 were found in the cryoprecipitate. Their compositions were similar among patients with or without HCV. Few clinical features were associated with the presence of cryoglobulins, including deep venous thrombosis, cutaneous purpura and peripheral neuropathy. In conclusion, cryoglobulinemia was prevalent in kidney transplant recipients, but appeared to not affect graft function. HCV infection was the most frequently associated etiology and clinical features were infrequent.

Common variable immunodeficiency.

We describe a patient with common variable immunodeficiency who three times presented an anaphylactic reaction after intravenous immunoglobulin administration. These reactions were attributed to the total absence of IgG 2, 3 and 4.

Serum IgE level in malnutrition.

UNLABELLED: Infections and malnutrition remain the main causes of infant mortality in developing countries. In protein-calorie malnutrition, immunologic responses are affected, which often facilitates infections. However, the presence of asthma and allergic rhinitis are not commonly recognized in malnourished individuals. The aim of this study was to evaluate serum IgE values in children with primary moderate protein-calorie malnutrition. METHODS: The level of IgE in peripheral blood of 18 children between 2 and 4 old with moderate protein-calorie malnutrition and without associated parasitic infestation was compared with that of 15 well nourished children of similar age. IgE serum levels were measured by an immunoenzymatic method. RESULTS: The median level of serum IgE in malnourished children was 69.30 ng/ml while the control group showed a mean level of 95.97 ng/ml. This difference was significant (p < 0.01). CONCLUSION: Malnourished children show decreased serum IgE levels. This might be one of the adaptive mechanisms of malnutrition employed in an attempt to use energy and protein reserves for growth and other functions. Our results are coherent with the decrease in IgE mediated reactions in malnourished patients.

Atopic dermatitis with mononuclear phagocytic activity deficiency.

Five patients with atopic dermatitis, three males and two females, aged 2 to 17 years, had positive reactions to air allergens (Dermatophagoides pteronyssinus and/or farinae). All the patients suffered from severe recurrent dermatophytosis that responded poorly to antifungal treatment. The results of immunologic evaluation by laboratory tests were normal, except for a decrease in the ingestion phase by mononuclear phagocytes. After diagnosis of immunodeficiency, ketoconazole shampoo was used prophylactically and at the very first signs of recurrence of dermatophytosis, systemic antifungal treatment was started, without concurrent use of macrolides and with monitoring of hepatic function. The fungal infections responded well to this treatment and the patients' quality of life markedly improved.

Immunologic evaluation in infective endocarditis.

OBJECTIVE: To analyze the immune response in peripheral blood of patients with infective endocarditis. METHODS: We studied 10 patients with infective endocarditis, age range from 20 to 50 years-old, males and females, and 20 healthy subjects in the same age range. The diagnosis of the disease was based on the clinical picture, echocardiogram, and hemoculture based upon samples drawn and tested before the treatment started. The were no history of atopy or malnutrition, no autoimmune disease, and they were not using any immunosuppressant or antibiotic medication. RESULTS: The patients with endocarditis had significantly higher T and B lymphocyte, CD4+ and CD8+ cell counts, IgM and IgG serum levels, and C4 component of the complement than the control group; no significant difference concerning serum IgA and neutrophil oxidative metabolism; a significant decrease in C3, chemotaxis, and monocyte phagocytosis;cryoglobulins were detected in 66.6% of patients and they were formed by IgG, IgM, IgA, C3, and C4. CONCLUSION: The patients with infective endocarditis were immunocompetent in most sectors of immune response and, at a certain moment, an autoimmune component may be present.

[Positive skin test and age] / Testes cutâneos de hipersensibilidade imediata com o evoluir da idade.

OBJECTIVE: To evaluate positive responses to skin tests for immediate hypersensitivity to allergens in children with asthma and rhinitis at different ages. METHOD: We observed positive skin test reactivity in prick tests using fifteen allergens of same origin (total dust and Dermatophagoides sp.; Dermatophagoides pteronyssinus; Dermatophagoides farinae; Blomia tropicalis; Penicillium sp; Alternaria alternata; Cladosporium herbarium; Aspergillus fumigatus; Bermuda grass; forage grass; dog and cat epithelia; feathers; Blatella germanica and wool). We placed 713 selected patients into different age groups - Group I: 6 to 11 months; Group II: 1 to 3 years and 11 months; Group III: 4 to 8 years and 11 months; and Group IV: 9 to 15 years. We used the chi-square test for statistical analysis. RESULTS: The total significant differences between these groups were: I to II = 5; II to III = 5; II to IV = 5; III to IV = 6; I to III = 10; and I to IV = 10. CONCLUSION: Skin test reactivity is acquired progressively with age, and can be observed as early as at 12 months. Reactivity is significantly more positive from the age of 4 on.

Repeated furunculosis in adult male with abnormal neutrophil activity.

A 21 years old male suffered from repeated furunculosis in different regions of the body over the last two years. This coincided with the start of professional activities in hospital surroundings. The purulent secretions all showed growth of Staphylococcus aureus. All laboratory tests were normal except for a decrease of the neutrophil phagocytic ingestion phase. Before the diagnosis of defective phagocytosis was made, antibiotic treatment was started about 4 to 5 days after the appearance of the infectious process and the furunculosis led to abscess formation with difficult healing and cellulitis. After the diagnosis of defective phagocytosis ingestion phase, personal hygiene was intensified during and after work shifts at the hospital and antibiotic treatment was started at the first signs of folliculitis, which showed healing.

[Evaluation of polymorphonuclear neutrophils in moderate malnutrition]. / Avaliação de neutrófilos na desnutrição moderada.

PURPOSE: To evaluate the phagocytic function of polymorphonuclear neutrophils in moderate malnutrition. METHODS: The phagocytic function of neutrophils obtained through peripheral blood sampling of twenty two children with moderate malnutrition without infections was analyzed. The results were compared to a group of twenty well nourished children matched for age (two to five years old). The phagocytic function was assessed by the ingestion of zymosan particles and nitro blue tetrazolium reduction among 200 cells. RESULTS: The mean number of zymosan particles ingested by neutrophils incubated with homologous human serum and autologous human serum were 18, 41 and 46 in the malnutrition group compared to 20, 57 and 63 in the well nourished group. The spontaneous and stimulated reduction of nitro blue tetrazolium was 6 and 11 in the malnourished patients, respectively, and 12 and 17 in the well nourished group. CONCLUSION: A decrease in the process of ingestion and digestion during phagocytosis occurs in malnourished patients.

Avaliaçäo de neutrófilos na desnutriçäo moderada / Evaluation of polymorphonuclear neutrophils in moderate malnutrition

Objetivo. Avaliar a etapa de ingestao da fagocitose e do metabolismo oxidativo de neutrófilos em crianças portadoras de desnutriçao moderada. Métodos. Foi analisado o sangue periférico de vinte e duas crianças portadoras de desnutriçao moderada, sem infecçao, comparando-se os resultados aos de vinte crianças eutróficas da mesma faixa etária (2 a 5 anos de idade). A ingestao fagocitária por neutrófilos foi avaliada através da ingestao de partículas de zimosan e o metabolismo oxidativo avaliado pela reduçao do nitro blue tetrazolium entre um número fixo de 200 neutrófilos. Resultados. As médias aritméticas da ingestao por neutrófilos de partículas de zimosan, zimosan incubado com soro homólogo e zimosan incubado com soro autólogo foram 18, 41 e 46 em desnutridos e 20, 57 e 63 em eutróficos. A reduçao espontânea e estimulada de nitro blue tetrazolium foi de 6 e 11 em desnutriçao e 12 e 17 em eutróficos. Conclusao. Concluiu-se haver uma diminuiçao da etapa da ingestao e do metabolismo oxidativo de neutrófilos nos pacientes estudados portadores de desnutriçao moderada.

Complement system in malnutrition.

The total complement and C3 and C4 components serum levels were assessed in vitro in forty children suffering from severe and moderate protein-calorie malnutrition in the 2 to 5 year age group. Twenty well-nourished children of the same age were as a control group. The results in the three group showed no significant differences.