Proposal to Screen for Zinc and Selenium in Patients with IgA Deficiency.

The increase in life expectancy can be a consequence of the world's socioeconomic, sanitary and nutritional conditions. Some studies have demonstrated that individuals with a satisfactory diet variety score present a lower risk of malnutrition and better health status. Zinc and selenium are important micronutrients that play a role in many biochemical and physiological processes of the immune system. Deficient individuals can present both innate and adaptive immunity abnormalities and increased susceptibility to infections. Primary immunodeficiency diseases, also known as inborn errors of immunity, are genetic disorders classically characterized by an increased susceptibility to infection and/or dysregulation of a specific immunologic pathway. IgA deficiency (IgAD) is the most common primary antibody deficiency. This disease is defined as serum IgA levels lower than 7 mg/dL and normal IgG and IgM levels in individuals older than four years. Although many patients are asymptomatic, selected patients suffer from different clinical complications, such as pulmonary infections, allergies, autoimmune diseases, gastrointestinal disorders and malignancy. Knowing the nutritional status as well as the risk of zinc and selenium deficiency could be helpful for the management of IgAD patients. OBJECTIVES: to investigate the anthropometric, biochemical, and nutritional profiles and the status of zinc and selenium in patients with IgAD. METHODS: in this descriptive study, we screened 16 IgAD patients for anthropometric and dietary data, biochemical evaluation and determination of plasma and erythrocyte levels of zinc and selenium. RESULTS: dietary intake of zinc and selenium was adequate in 75% and 86% of the patients, respectively. These results were consistent with the plasma levels (adequate levels of zinc in all patients and selenium in 50% of children, 25% of adolescents and 100% of adults). However, erythrocyte levels were low for both micronutrients (deficiency for both in 100% of children, 75% of adolescents and 25% of adults). CONCLUSION: our results highlight the elevated prevalence of erythrocyte zinc and selenium deficiency in patients with IgAD, and the need for investigation of these micronutrients in their follow-up.

Novel variant of common variable immunodeficiency.

A 57-year-old woman with frequent respiratory infections was initially diagnosed with IgG subclass deficiency based on low levels of IgG subclasses 2 and 3. Three years later, she progressed to having IgA deficiency as well. With a normal total IgG level, she does not meet criteria for common variable immunodeficiency (CVID). This may represent a variant of CVID. This also highlights the importance of immunoglobulin subclass estimation in patients where immunodeficiency is suspected clinically. She is being treated with rotational antibiotics the first 10 days of every month, monthly intravenous immunoglobulin (IVIG) infusion and osteopathic manipulation one to two times per month. On this regimen, although she has had several viral respiratory infections, she has avoided further hospitalisation for more than 1 year.

Implementation of National Institute for Health and Care Excellence (NICE) guidance to measure immunoglobulin A with all coeliac screens: can an affordable solution be devised?

There has been a dramatic increase in requests for coeliac disease (CD) serological screening using immunoglobulin (Ig)A tissue transglutaminase antibodies (IgA-tTG). Recently, the UK National Institute for Health and Care Excellence has revised its guidance, recommending that total IgA should also be measured in all samples. This is justified, as false-negative results may occur with IgA deficiency. However, implementation of this guidance will incur considerable expense. Tests that measure IgA-tTG antibodies can detect IgA deficiency, indicated by low background signal. This provides an opportunity to identify samples containing IgA ≤ 0·2g/l, obviating the need for unselected IgA measurement. We investigated the feasibility of this approach in two centres that use the EliA™ Celikey™ assay or QUANTA Lite® enzyme-linked immunosorbent assay to quantify IgA-tTG antibodies. In both cases, total IgA correlated strongly with background IgA-tTG assay signal. Using the Celikey™ assay, a threshold of < 17·5 response units achieved 100% sensitivity (95% confidence intervals 79·4-100%) for detection of IgA ≤ 0·2g/l, circumventing the need for IgA testing in > 99% of sera. A similar principle was demonstrated for the QUANTA Lite® assay, whereby a threshold optical density of < 0·0265 also achieved 100% sensitivity (95% confidence intervals 78·2-100%) for IgA ≤ 0·2 g/l, avoiding unnecessary IgA testing in 67% of cases. These data suggest that CD screening tests can identify samples reliably containing low IgA in a real-life setting, obviating the need for blanket testing. However, this approach requires careful individualized validation, given the divergent efficiency with which assays identify samples containing low IgA.

Enfermedad celíaca: ¿qué características tienen nuestros pacientes en el momento del diagnóstico? / Celiac disease: what characteristics do our patients have at the time of diagnosis?

Introducción: la enfermedad celíaca es una patología crónica que con frecuencia presenta los primeros síntomas en la edad pediátrica. En los últimos años ha aumentado el número de diagnósticos, a la vez que se ha reducido la edad a la que se realizan estos. Material y métodos: estudio descriptivo de los antecedentes y las características epidemiológicas, clínicas y diagnósticas de 102 pacientes controlados por enfermedad celíaca en un hospital de tercer nivel. Resultados: el 41,4% son varones y el 58,6% mujeres, la mayor parte de etnia caucásica (94,1%). El 9,8% tienen al menos un familiar de primer grado celíaco, y el 6,9% de segundo grado. La edad media al diagnóstico es 42,8 ± 35,9 meses. El 89,2% presentaban algún síntoma al diagnóstico, mientras en el 10,8% restante el diagnóstico se obtuvo en el cribado de celiaquía por presentar otra patología asociada. Síntomas más frecuentes: pérdida de peso (58%), diarrea (52%), hiporexia (40%), distensión abdominal (24%), alteración del carácter (15%), hábito malabsortivo (13%) y dolor abdominal (12%). Estudio serológico: el 95% presentó anticuerpos antitransglutaminasa positivos, el 85,2% antiendomisio positivos, el 88,4% antigliadina IgG positivos. Estudio del sistema de antígenos leucocitarios humanos (HLA): 97% DQ2, 2% DQ8. Se realizó biopsia duodenal al 62,8% (3% Marsh I, 5% Marsh II, 17% Marsh IIa, 17% Marsh IIIb, 58% Marsh IIIc). Conclusiones: el mayor conocimiento de la enfermedad celíaca podría haber influido en la baja edad media al diagnóstico en la muestra. La aplicación de los criterios diagnósticos de la ESPGHAN de 2012 ha permitido diagnosticar a un relevante número de pacientes sin realizar biopsia (AU)

Introduction: celiac disease is a chronic pathology that often presents the first symptoms in childhood. Diagnoses of celiac disease have increased in recent years, while the age of diagnosis has reduced. Methods: 102 patients with celiac disease controlled in a tertiary hospital. Descriptive study of personal history, epidemiology, symptoms and diagnosis. Results: 41.4% were male and 58.6% female, most of Caucasians (94.1%). 9.8% had at least one first-degree relative celiac, and 6.9% in second degree. The average age at diagnosis is 42.8±35.9 months. 89.2% had symptoms at the moment of diagnosis, while the remaining 10.8% was obtained in the diagnosis of celiac disease screening to present other associated pathology. Common symptoms: weight loss (58%), diarrhea (52%), lack of appetite (40%), abdominal distension (24%), alteration of the character (15%), malabsorptive habit (13%) and abdominal pain (12%). Serological study: 95% positive transglutaminase antibodies, 85.2% positive endomysial antibodies, 88.4% positive anti-gliadin IgG antibodies. HLA study: 97% DQ2, DQ8 2%. Duodenal biopsy was performed to 62.8% (3% Marsh I, 5% Marsh II, 17% IIa Marsh, 17% Marsh IIIb, 58% IIIc Marsh). Conclusions: Increased knowledge about celiac disease among general pediatricians may have influenced the low average age at diagnosis in our sample. The application of diagnostic criteria ESPGHAN 2012 have allowed a significant number diagnoses patients without performing a biopsy (AU)

El impacto social y económico de la ozonoterapia en la deficiencia de inmunoglobulina A / The social and economic impact of ozone therapy in immunoglobulin A deficiency

La concepción social de la ciencia y el desarrollo tecnocientífico de la medicina en Cuba se abordan en este artículo a través del enfoque social de la ozonoterapia en la deficiencia de inmunoglobulina A. Se enfatiza en el papel determinante del contexto social en la aplicación de la ciencia y la tecnología. Se describen los aportes sociales, económicos y científicos de la terapia con ozono en esta enfermedad inmunológica y se demuestra como el desarrollo tecnocientífico de la medicina cubana ha permitido realizar la investigación clínica. La terapia con ozono tuvo gran impacto en la salud de los niños deficientes de Immunoglobulin A lo que representa un fuerte beneficio social (AU)

The social conception of science and techno-scientific development of medicine in Cuba addressed in this article through the social approach of ozone therapy in immunoglobulin A deficiency. It is emphasized the crucial role of social context in the application of science and technology. Social, economic and scientific contributions of ozone therapy in this immunologic disease are described and it is shown how the scientific development of Cuban medicine has allowed clinical research. Ozone therapy had great impact on the children´s health with IgA deficiency which represents a strong social benefit (AU)

The effect of bovine colostrum on viral upper respiratory tract infections in children with immunoglobulin A deficiency.

INTRODUCTION: Immunoglobulin A (IgA)-deficient patients predominantly suffer from respiratory and gastrointestinal infections since secretory IgA has important functions to protect mucosal surfaces. OBJECTIVE: To evaluate the effect of bovine colostrum, rich in IgA, on the treatment of viral upper respiratory tract (URT) infections in IgA-deficient children. METHODS: Thirty-one IgA-deficient children with viral URT infections were included in this double-blind, placebo-controlled study, and randomly oral bovine colostrum or placebo was given three times a day for 1 week. Samples of saliva IgA were collected before treatment, after the administration of the first dose, and after the last dose. Mothers of the children completed a daily questionnaire regarding the severity of the infection and any adverse effects. RESULTS: The bovine colostrum group had a lower infection severity score than the placebo group after 1 week (respectively 0.81±0.83, 3.00±1.85; P=0.000), but there was no difference between the salivary IgA levels of the groups. CONCLUSION: This is the first study to evaluate the effect of bovine colostrum in IgA-deficient children, and no adverse effects were observed. However, further studies are needed to confirm the efficacy and safety of bovine colostrum in IgA-deficient patients.

Immune status is more affected by age than by carotenoid depletion-repletion in healthy human subjects.

Prospective studies have indicated an age-related impairment of the immune response. Carotenoids have been hypothesised to enhance immune cell function. The aim of the present study was to describe the age-related effects and the impact of in vivo dietary carotenoid depletion and repletion on specific and non-specific immunity. A total of ninety-eight healthy male subjects (aged 20-75 years) received a carotenoid-depleted diet for 3 weeks and were then supplemented daily for 5 weeks with 30 mg ß-carotene, 15 mg lycopene and 9 mg lutein. Blood samples were collected at study entry, after depletion and supplementation, and biomarkers of immune status were determined. We found that serum IgA levels were positively correlated with ageing. Lymphocyte phenotyping indicated an increase with age in the memory T-helper cell subpopulation (CD4⁺CD45RO⁺) concomitantly with a decrease in naive T-helper cells (CD4⁺CD45RA⁺). A significant increase in the natural killer cells subpopulation and a small decrease in B lymphocytes were also observed, especially for the oldest volunteers. From ex vivo cell function exploration, a positive correlation was observed between age and IL-2 production of phytohaemagglutinin-stimulated lymphocytes. Neutrophils' bactericidal activity was significantly impaired with age (from 50 years) and was modulated by carotenoid status. An age effect was found on neutrophils' spontaneous migration but not on directed migration. Immune response in healthy human subjects is mostly affected by age rather than by dietary carotenoid depletion and repletion. Even in carefully selected healthy volunteers, some age-related immune changes occur predominantly from 50 years onwards. This immunosenescence could generate a loss in the immune system adjustment capacity.

Deficiência de IgA associada a Artrite reumatoide juvenil / IgA deficiency and Juvenile rheumatoid arthritis

Objetivo: descrever um caso de deficiência de IgA associado a artrite reumatoide juvenil e infecções de repetição.Relato do caso: paciente de 12 anos, sexo feminino, com diagnóstico de artrite reumatoide juvenil associada a infecção pulmonar grave. A deficiência de IgA foi suspeitada e o diagnósticoconfirmado através da dosagem de IgA sérica.Conclusão: os médicos devem estar atentos ao diagnóstico de deficiência de IgA pela grande associação não só com processos infecciosos e alérgicos, mas, também com doenças auto imunes.

Objective: to describe a case of IgA deficiency and juvenile rheumatoid arthritis and recurrent infections.Case report: a 12 year-old patient, female, diagnosed with juvenile rheumatoid arthritis associated with severe lung infection. IgA deficiency was suspected and the diagnosis was confirmed through serum IgA measurement.Conclusion: physicians should be aware of the diagnosis of IgA deficiency no only beca use of its close association with infectious and allergic processes, but also with auto immune diseases.

Ineffectiveness of folic acid supplementation against phenytoin-induced decrease in salivary immunoglobulin A concentration of epileptic patients.

AIMS: This study was designed to investigate if folate treatment is able to reverse the phenytoin-induced deficiency of salivary immunoglobulin A (IgA). METHODS AND MATERIAL: Twenty-five epileptic patients who had been under phenytoin therapy for at least the last 6 months were randomly selected and subjected to folic acid supplementation, 1 mg/day. The salivary IgA concentration of these patients was measured before and after 2 months of folic acid administration and compared with those of 10 healthy individuals. Independent and paired Student's t tests were used to analyze the effects of phenytoin and folic acid, respectively. RESULTS: Salivary IgA levels of patients receiving phenytoin (11.7 +/- 4.8 IU/l) were significantly (p = 0.039) lower than those of healthy controls (14.8 +/- 3.2 IU/l), but did not statistically (p = 0.541) differ from levels (11.8 +/- 4.6 IU/l) measured after 2 months of folic acid supplementation. CONCLUSIONS: According to these results, folic acid supplementation does not seem to have the efficacy to ameliorate phenytoin-induced salivary IgA hyposecretion.

Recovery from experimental malnutrition with soymilk: immunological and genetic aspects / Recuperación de la malnutrición experimental con leche de soja: aspectos inmunológicos y genéticos

Experimental malnutrition models have been useful to study the effects of malnutrition at early ages. Substantial evidence exists that malnutrition in critical stages of development could result in chromosomal damages. The effect of nutritional rehabilitation with soymilk as a complement of a restricted diet, on plasma and muscle proteins, chromosomal integrity, and unspecific and mucosa immune responses, was studied. Adult male and female Wistar rats (5 weeks old) were assigned to different nutritional conditions: a) 14 days on protein restricted diet (corn flour and water), followed by 14 days in which water was replaced by soymilk, as nutritional rehabilitation; b) the same conditions above but periods of 28 days of a protein restricted diet, and 28 days of nutritional rehabilitation and c) age-matched malnourished (protein restricted diet without nutritional rehabilitation) and normally nourished controls. After both nutritional rehabilitation periods, the weights reached were significantly higher (p < 0.001) than the malnourished control values, but lower than the normal control ones. Plasma protein concentrations were similar in all groups. Muscle proteins that were diminished during the restricted diet, reached normal control values after both rehabilitation periods. The protein restricted diet, produced numeric and structural chromosomal abnormalities. Nutritional rehabilitation was only partially able to revert these abnormalities. The phagocytic activity and gut mucosa IgA-secreting cells were significantly reduced (p < 0.001) during the restricted diet; both nutritional rehabilitation periods induced a significant increase of both, phagocytic activity and IgA secreting cells. These values were similar to controls. Our results show that the supplementation of a protein- restricted diet with soymilk improved tissue protein content, as well as unspecific and gut mucosa immune responses, even though it was not able to reinstate fully normal body weight and a normal chromosome karyotype

Los modelos de malnutrición experimental han sido útiles para estudiar los efectos de la misma en edades tempranas. Hay evidencia sustancial de que la malnutrición en etapas críticas del desarrollo podría producir daños cromosómicos. Se estudió el efecto de la rehabilitación nutricional con leche de soja como complemento de una dieta restringida sobre las proteínas plasmáticas y musculares, la integridad cromosómica y las respuestas inmunitarias inespecíficas de las mucosas. Se asignaron ratas Wistar adultas macho y hembra (5 semanas de edad) a distintas condiciones nutritivas: a) 14 días con una dieta de restricción de proteínas (harina de maíz y agua), seguida de 14 días en los que se reemplazó el agua por leche de soja, como rehabilitación nutricional; b) las mismas condiciones anteriores pero con períodos de 28 días de dieta con restricción de proteínas y 28 días de rehabilitación nutricional; c) controles desnutridos (dieta de restricción proteica sin rehabilitación nutricional) y adecuadamente nutridos, emparejados por edad. Tras ambos períodos de rehabilitación, los pesos alcanzados fueron significativamente superiores (p <0,001) que las cifras en los controles desnutridos, pero inferiores a las de los controles normales. La concentración plasmática de proteínas fue similar en todos los grupos. Las proteínas plasmáticas, que estaban disminuidas durante la restricción dietética, alcanzaron los valores de los controles normales tras ambos períodos de rehabilitación. La dieta con restricción proteíca produjo anomalías en el número y estructura de los cromosomas. La rehabilitación nutricional sólo pudo revertir parcialmente estas anomalías. La actividad fagocítica de las células intestinales productoras de IgA estaba significativamente disminuida (p < 0,001) durante la dieta restringida; ambos períodos de rehabilitación nutricional produjeron aumentos significativos de ambos parámetros. Estos valores eran similares a los controles. Nuestros resultados muestran que la complementación con leche de soja de una dieta restringida en proteínas mejoró el contenido tisular de proteínas así como las respuestas inmunitarias inespecíficas y de la mucosa intestinal, aunque no fue capaz de restablecer por completo a la normalidad el peso corporal y el cariotipo cromosómico

Malignant otitis externa in an infant with selective IgA deficiency: a case report.

The occurrence of malignant otitis externa (MOE) in infancy is rare. We report a case of MOE in a neonate who was later identified to have selective IgA deficiency. She was successfully treated with oral ciprofloxacin, but developed external auditory canal stenosis, a deformed pinna, persistent facial nerve palsy, temporal bone erosion and hearing loss. No cases of MOE in selective IgA deficiency have been reported in literature. This is also the first report on the use of ciprofloxacin in infants with MOE.

Trends in donor milk banking in the United States.

Modern donor milk banking was conceived in the US in the early 1900s as a medicalized version of wet nursing. Over the course of the century the fortunes of donor milk banking have varied considerably. In the last 20 years donor milk banking has been negatively affected by the development of specialty formulas, safety issues related to viral transmission, and lack of clinical research. To survive, US milk banks have been receptive to clinical uses considered as "alternative medicine," and have cooperated with governmental agencies to develop standards for safety. A qualitative analysis of collected case histories of US donor milk recipients demonstrates that donor human milk banking can be critical to survival and the well-being of at-risk infants, children, and the occasional adult. By analyzing national data collected by survey method and examining the literature, the researcher compared German and US milk banks and distribution data. German milk banks use donor milk exclusively for premature infants and have less stringent operating standards, yet dispense volumes of milk greatly in excess of the US milk banks. While statistics are lacking for the total recipient population in the US, a projected analysis (based on German consumption) of the potential volume that could be dispensed in the US is presented, indicating that the population in need of this crucial public health service is currently under-served in the US.

Epithelial changes in seasonal allergic rhinitis throughout the year: evidence of coexistent air pollution and local secretory IgA deficiency?

To determine possible epithelial changes in seasonal allergic rhinitis, we examined epithelial cells in cytology swab preparations of 38 non-smoking patients, exclusively sensitized to grass pollen, throughout the year, and surgical material of 8 patients. Cytologically, we found a marked goblet cell hyperplasia during the period of grass pollen exposure, while meta- and dysplasia were found throughout the year. Immunohistochemically, a lack of secretroy IgA in the altered epithelium was detected. These results were not obtained in the control group of 60 healthy non-smokers. Since we have recently found the same epithelial changes of meta- and dysplasia in smokers, these findings may point to non-specific toxic damage of the nasal epithelium possibly caused by other air pollutants. The altered epithelium may lead to an impairment of the local secretory IgA defence system and thereby to an increased allergen uptake.

Manifestaciones articulares en inmunodeficiencias primarias / Articular manifestations in primary immunodeficiencies

Las inmunodeficiencias primarias constituyen entidades clínicas que, aun cuando se presentan esporádicamente en la práctica diaria, suelen acompañarse de gran morbilidad y mortalidad si no se efectúan un diagnóstico y un tratamiento oportunos. Algunas de estas inmunodeficiencias pueden iniciar su sintomatología con manifestaciones articulares que semejan un proceso reumatológico. De las numerosas inmunodeficiencias primarias descritas hasta la fecha, la hipogamaglobulinemia común variable es la entidad que con más frecuencia se asocia con estas manifestaciones. La enfermedad se caracteriza por una deficiencia severa en la producción de anticuerpos, lo que conduce a infecciones bacterianas recurrentes. En tanto, ciertas condiciones predisponentes para algunas enfermedades reumatológicas, tales como Lupus eritematoso Diseminado, Vasculitis, Nefropatía y otras. El conocimiento de estas condiciones inmunológicas reviste una gran importancia en la patogenia y manejo de las enfermedades reumatológicas

The IgA-deficient blood donor: something in the air?

In May 1994, the Blood Transfusion Centre, Sheffield, introduced a new screening test for Immunoglobulin A (IgA) deficiency. The test is performed in parallel with routine donor ABO grouping and Rh typing on two Olympus PK 7200 autoanalysers. A panel of IgA-deficient donors is required to provide blood products for IgA-deficient patients in whom the presence of anti-IgA antibodies may cause serious anaphylactic transfusion reactions (Welborn & Hersch, 1991). Detection rates during high summer became noticeably inconsistent and since a relationship between IgA deficiency and hypersensitivity states is recognized (Amman & Hong, 1971), a comparison between the detection rate and pollen levels during June and July 1994 was undertaken; the results of this study are presented here.

Oral conditions in individuals with selective immunoglobulin A deficiency and common variable immunodeficiency.

Saliva and serum samples were collected from 36 individuals with selective immunoglobulin A deficiency (IgAd) and 23 patients with common variable immunodeficiency (CVI). The oral examination included registration of the teeth, Russell's periodontal index (PI), pocket formation, and salivary flow rate in both unstimulated and stimulated saliva. No differences were found in salivary flow rate, number of teeth, or pocket depth when donors with IgAd or CVI were compared to age and sex matched controls. However, mucosal manifestations of lichenoid type were more frequent in both types of immunoglobulin deficient individuals. An increased PI was also seen in CVI patients. Increased serum IgG and salivary IgM levels were found in the IgAd population.

Rhabdomyolysis after intramuscular iron-dextran in malabsorption.

The case of a 59 year old white man who had chronic malabsorption and selective IgA deficiency with severe iron deficiency is reported. In addition, he was deficient in vitamin E and selenium, important antioxidants which protect against lipid peroxidation. He was intolerant of oral iron and when treated with iron-dextran developed symptoms suggestive of polymyositis with evidence of rhabdomyolysis. It is suggested that free iron within iron-dextran activated free radicals, initiating lipid peroxidation and leading to polymyositis, rhabdomyolysis, and myoglobulinuria.

Bacterial overgrowth after high-dose corticosteroid treatment.

A 63-year-old man with systemic lupus erythematosus and selective IgA deficiency developed intractable diarrhoea the day after treatment with prednisone, 50 mg daily, was started. The diarrhoea was considered to be caused by bacterial overgrowth and was later successfully treated with doxycycline. Although IgA deficiency is a risk factor for bacterial overgrowth, a further predisposing condition is necessary for development of this disorder but was not present in this case. We therefore suppose that high-dose treatment with corticosteroids might be a hitherto undescribed risk factor for bacterial overgrowth in vulnerable patients.