Immunoglobulin G4-Related Disease: What an Allergist Should Know.

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder that begins in 1 or more organs as inflammatory tumors that progress toward fibrosis. It is often accompanied by elevated serum IgG4. IgG4-RD was first described in 2003 as a new concept encompassing a number of immunoallergic diseases that had previously been considered unrelated. IgG4-RD mainly affects middleaged and older men. It consists of upregulation and expansion of CD4+ cytotoxic T lymphocytes, oligoclonal plasmablasts, and other inflammatory cells that infiltrate affected tissues and induce inflammation, organ dysfunction, and fibrosis. Symptoms depend on the location, severity, and extent of the disease. Virtually any organ can be affected, including the pancreas, salivary glands, lacrimal glands, thyroid gland, retro-orbital tissue, lymph nodes, retroperitoneum, mediastinum, lung, kidney, aorta, serosal surfaces, and meninges. Patients with widespread disease may present general symptoms. At least 30%-40% of patients are atopic or display atopic traits such as eosinophilia and elevated serum IgE levels. Additional laboratory features include increased serum IgG4 concentrations, increased blood IgG4-plasmablasts, hypergammaglobulinemia, and hypocomplementemia. Diagnosis of IgG4-RD is based on a clinicopathological correlation. Lymphoplasmacytic infiltrate with abundant IgG4-positive plasma cells, storiform-type fibrosis, obliterative phlebitis, and tissue eosinophilia are the pathological hallmarks. Therapy for IgG4-RD is based primarily on corticosteroids but may include additional immunomodulatory drugs and monoclonal antibodies such as rituximab. In individuals with allergic features, IgG4-RD should be suspected when a history of unexplained swelling is observed in 1 or more organs, particularly if they respond to corticosteroids and the patients are men in the sixth decade of life and beyond.

False-Positive Results of Serological Tests for Allergy in Alcoholic Patients.

BACKGROUND AND OBJECTIVE: Alcohol consumption is associated with enhanced TH2 immune responses. Objective: To investigate the frequency of false-positive results in serological tests for allergy in alcoholic patients. METHODS: A total of 138 alcoholic patients consecutively admitted to hospital underwent a panel of allergy tests that included serum total IgE, a multiallergen IgE test (UniCAP Phadiatop), and skin prick tests to relevant aeroallergens in the area, which were considered the standard reference for atopy. In selected cases with positive specific IgE (sIgE) to cross-reactive carbohydrate determinants (CCDs) on ImmunoCAP, we determined sIgE to hymenoptera venom components (ADVIA Centaur) and a microarray of 103 allergen components (ISAC). RESULTS: Increased serum total IgE (>170 IU/mL) was observed in 59/110 (54%) of nonatopic (skin prick test-negative) patients. The result of the multiallergen IgE test was positive in 46 nonatopic patients (42%). This finding was closely associated with high serum concentrations of total IgE and sIgE to CCDs. The vast majority of patients with positive CCD-sIgE showed positivity to glycosylated plant and hymenoptera allergen components on ISAC and ADVIA Centaur. Only 1 out of 26 patients with positive sIgE to CCD and hymenoptera venom developed honeybee venom allergy after a median follow-up of 166 months. Correlations between measurements of sIgE to CCD markers on ImmunoCAP, ADVIA Centaur, and ISAC were imperfect. CONCLUSIONS: Serological tests for allergy should be interpreted with caution in alcoholic patients, who frequently have increased levels of total IgE and CCD-sIgE and subsequent positivity of sIgE to glycosylated allergen components, irrespective of the method used.

Factors Influencing Serum Concentrations of Immunoglobulin D in the Adult Population: An Observational Study in Spain.

Immunoglobulin D (IgD) is the least studied of immunoglobulin classes. This study sought to investigate the potential relationship between demographic, metabolic, lifestyle and immunological factors, and serum IgD concentrations in a general adult population. We measured serum IgD concentrations by means of a commercial turbidimetric assay in 413 individuals (median age, 55 years; 45% males), randomly selected from the adult population of a Spanish municipality. Serum IgD concentrations displayed considerable variation in the population, ranging from undetectable (<6.7 mg/l) to 878 mg/l. Serum IgD concentrations were undetectable in 78 cases (18.9%) and >100 mg/l in 39 cases (9.4%). Median IgD was 21.9 mg/l. Serum IgD concentrations were negatively associated with age and positively associated with smoking, after adjustment for potential confounders. Overweight individuals showed lower concentrations of IgD than did normal-weight individuals. Atopy (positivity of skin tests to aeroallergens) was not significantly associated with IgD concentrations, although non-symptomatic atopics showed higher IgD concentrations. No consistent association was observed between serum IgD concentrations and gender, metabolic syndrome, or alcohol consumption. No significant association was found between baseline IgD concentrations and development of either allergic or immune disease after a median 11.4 years of follow-up. In conclusion, serum IgD concentrations in adults show a wide variation in the population and may be influenced by common factors, particularly age and smoking habit. These factors should be taken into account when defining reference ranges for serum IgD concentrations.

Safety of measles-mumps-rubella vaccine (MMR) in patients allergic to eggs.

INTRODUCTION: Since the measles and mumps components used in MMR vaccine are grown in cultures of fibroblast from chick embryos, for a long time there have been concerns about the presence of egg protein in the vaccine and the recommendations given to egg allergic patients. We include in this paper our clinical experience vaccinating egg allergic patients with a regular triple viral vaccine, as well as an immunological study of each vaccine available in Spain. The aim of this study was to evaluate the clinical safety of a conventional MMR vaccine in a population of egg allergic patients and to determine the presence of egg allergens in a conventional MMR vaccine and if IgE antibodies from egg allergic can recognize egg allergens in this vaccine. MATERIALS AND METHODS: Children 15 months old with a confirmed diagnosed of egg allergy were included. In all patients, a skin prick test with non diluted MMR vaccine (Priorix, GSK) was made. If negative, each patient received a single dose of measles, mumps, rubella (MMR) vaccine. If positive, a fractionated injection of the vaccine was made following SEICAP recommendations (2004). SDS-PAGE immunoblotting was performed with Priorix vaccine. RESULTS: A cumulative total of 26 patients with egg allergy have safely received MMR vaccine in a single-dose (after a negative SPT in all cases) at our department without any reaction. 5 sera of vaccinated patients and 6 control sera of egg allergic patients (positive oral challenge) were used to immunolabel the membranes. No positive bands corresponding to egg proteins were found in any of the patients. CONCLUSION: Negative results found in SPT support the absence of clinical reaction against the components and Immunological studies point that there is no detectable amount of egg protein in this vaccine to produce an IgE mediated reaction. We can conclude that MMR can be safely administrated in children allergic to egg.

Osteosarcoma en niños y adolescentes: reporte definitivo del brazo pediátrico del grupo cooperativo venezolano para el estudio de los tumores óseos (GCVETO): octubre 1995-diciembre 1999 / Osteosarcoma in children and adolescen: report definitive of the arm pediatric of the group cooperative venexuelan for study od the tumors osseous (GCVETO): octuber 1995-december 1999

En 1995 se integró el GCVETO, y en octubre 1995 se inicia el Protocolo 003/95 para el estudio y tratamiento del Osteosarcoma (OS). Durante el período comprendido entre el 01.10.1995 y el 31.12.1999, 39 pacientes menores de 20 años ingresaron al brazo pediátrico del protocolo 003/95. El esquema de quimioterapia incluyó: Ifosfamida (IFOS)/Mesna 1800 mgr/m²/día/5 días, Doxorubicina (DOXO) 25 mgr/m²/día/3 días asociado a ICRF-187 (Desraxozane)250 mgr/m²/día/3 días, Cisdiaminodicloroplatino (CDDP) 40 mgr/m²/día/3 días. 64,10 por ciento eran varones, con una relación sexo V:H 1,78:1. 53,84 por ciento tenían edades comprendidas entre 10 y 15 años, edad mínima 6 a. y máxima 20 a., con un promedio de 12,53 a. Dolor, aumento de volumen e incapacidad funcional fueron los datos clínicos más frecuentes. 100 por ciento de los casos presentaban compromiso de partes blandas, y en 30,78 por ciento el volumen tumoral fue > 20 cm. El sitio de localización más frecuente: Femúr 48,7 por ciento, seguido por Tibia 23,07 por ciento y Húmero 20,51 por ciento. 14 pacientes presentaron enfermedad metastásica al ingreso. Las alteraciones de laboratorio más relevantes: Velocidad Sedimentación Globular (VSG), niveles séricos de Fosfatasa Alcalina (FA) y Deshidrogenasa Láctica (LDH). Los estudios imagenológicos del hueso comprometido fueron positivos en todos los casos, orientando el diagnóstico clínico en el 100 por ciento de los mismos. En todos los casos se estableció el diagnóstico a través del estudio histológico. 34 pacientes (87,18 por ciento) se consideraron evaluables para la terapia. Cirugía definitiva se realiza en el 61,76 de los casos: Injerto Oseo 11 pacientes, Desarticulación 8 pacientes, Resección tumoral 1 paciente, Amputación 1 paciente, Endoprótesis 1 paciente. 226 cursos de quimioterapia fueron administrados, promedio de 5,79 ciclos. 17 pacientes (50 por ciento) han finalizado la terapia. La respuesta histológica se evaluó según porcentaje de necrosis sólo en 16 pacientes (72,72 por ciento): Grado I 2/16, Grado II 3/16, Grado III 7/16, Grado IV 3/16, N.R. 6/22. R.C., fue obtenida en 19 pacientes (55,88 por ciento): 16/22 pacientes sin enfermedad metastásica y 3/12 con enfermedad metastásica. R.P. 13 pacientes, Progresión 2 pacientes, 8 pacientes fallaron a la terapia: Los sitios de recaída más frecuentes: Pulmón y Hueso (50 por ciento)