Familial IgG3 subclass deficiency: A report of two cases

Primary immunodeficiency in adults is thought to be underestimated in Korea. IgG subclass deficiency, defined as a deficiency at least among the 4 subtypes of IgG subclass, IgG1, IgG2, IgG3, and IgG4, results in recurrent infections, in which IgG3 subclass deficiency (IgGSD) is the most commonly found in adult asthmatic patients. Herein, we report 2 cases of familial IgG3SD. In family 1, a female patient aged 17 years with allergic rhinitis (AR) had recurrent upper respiratory infections (URIs), and gastroenteritis. Her mother aged 50 with AR had recurrent URI, otitis media, urinary tract infection, gastroenteritis, and oral ulcer. A younger sister aged 9 years with AR and asthma had recurrent URI almost all the year round. The serum IgA level was found to be lower than the normal level in her mother and the patient, and IgG3 was decreased in the patient and her sister. The IgG3 level of mother showed within the lower normal limit. In family 2, the mother aged 39 years with nonallergic rhinitis had recurrent URI and oral ulcer. Her son aged 16 years and daughter aged 13 years with AR and asthma had recurrent URI, resulting in uncontrolled asthma. Family 2 was found to be IgG3 deficiency in mother and son, and IgA deficiency in son. The IgG3 level of daughter was within the lower normal level. Mother and the first daughter in family 1 as well as mother and son in family 2 was treated with intravenous immunoglobulin, and their recurrent URI reduced. We reported 2 cases of familial IgG3SD.

Immunoglobulin G Subclass Deficiencies in Adult Patients with Chronic Airway Diseases

Immunoglobulin G subclass deficiency (IgGSCD) is a relatively common primary immunodeficiency disease (PI) in adults. The biological significance of IgGSCD in patients with chronic airway diseases is controversial. We conducted a retrospective study to characterize the clinical features of IgGSCD in this population. This study examined the medical charts from 59 adult patients with IgGSCD who had bronchial asthma or chronic obstructive pulmonary disease (COPD) from January 2007 to December 2012. Subjects were classified according to the 10 warning signs developed by the Jeffrey Modell Foundation (JMF) and divided into two patient groups: group I (n = 17) met ≥ two JMF criteria, whereas group II (n = 42) met none. IgG3 deficiency was the most common subclass deficiency (88.1%), followed by IgG4 (15.3%). The most common infectious complication was pneumonia, followed by recurrent bronchitis, and rhinosinusitis. The numbers of infections, hospitalizations, and exacerbations of asthma or COPD per year were significantly higher in group I than in group II (P < 0.001, P = 0.012, and P < 0.001, respectively). The follow-up mean forced expiratory volume (FEV1) level in group I was significantly lower than it was at baseline despite treatment of asthma or COPD (P = 0.036). In conclusion, IgGSCD is an important PI in the subset of patients with chronic airway diseases who had recurrent upper and lower respiratory infections as they presented with exacerbation-prone phenotypes, decline in lung function, and subsequently poor prognosis.

Immunoglobulin G (IgG) subclass deficiency in Thai children.

Background: Patients with Immunoglobulin G (IgG) subclass deficiency may suffer from recurrent infections, mainly sino-pulmonary infection. Objective: To determine the epidemiology of IgG subclass deficiency in Thai children at a tertiary care hospital and to compare the differences between children who were diagnosed with IgG subclass deficiency by using low level criteria [less than 2 standard deviation (SD) of normal levels for age] and by using low percentage criteria (proportion of each IgG subclasses/total IgG). Methods: The study was a descriptive study of 55 children up to 15 years old with recurrent infections diagnosed as having IgG subclass deficiency but no acquired or other primary immune deficiencies except for IgA and/or IgM deficiency. Result: Isolated IgG3 subclass deficiency was the most common IgG subclass deficiency (56.4%). IgG3 subclass deficiency, either isolated or combined with other IgG subclass deficiency, was found in 85.5% of the cases. The common age of onset was between birth and five years of age. The most common presenting symptom was recurrent sinusitis (83.6%). Majority of the cases (89.3%) were diagnosed by low percentage criteria while 12.7% were diagnosed by low level criteria. All cases with low levels of IgG subclass antibodies also had low percentages. There were no statistically significant differences in the clinical manifestations and management methods between the children who were diagnosed by low level and low percentage. Conclusion: IgG3 subclass deficiency was the most common IgG subclass deficiency in Thai children. The most common presenting symptom was recurrent sinusitis. Although the diagnosis could be made in the patients with recurrent upper respiratory infection by using low level criteria, but the diagnosis should be considered when the low percentage criteria are met.

Immunoglobulin G Subclass Deficiency is the Major Phenotype of Primary Immunodeficiency in a Korean Adult Cohort

Primary immunodeficiency disease (PID) is a rare disorder in adults. Most often, serious forms are detected during infancy or childhood. However, mild forms of PID may not be diagnosed until later in life, and some types of humoral immunodeficiency may occur in adulthood. The purpose of this study was to identify clinical features of PID in Korean adults. A retrospective study was performed on 55 adult patients who were diagnosed as PID between January 1998 and January 2009 at a single tertiary medical center in Korea. IgG subclass deficiency was the most common phenotype (67%, 37/55), followed by total IgG deficiency (20%, 11/55), IgM deficiency (7%, 4/55), common variable immunodeficiency (2%, 1/55), and X-linked agammaglobulinemia (2%, 1/55). IgG3 and IgG4 were the most affected subclasses. Upper and lower respiratory tract infections (76%) were the most frequently observed symptoms, followed by multiple site infection (11%), urinary tract infection, and colitis. Bronchial asthma, rhinitis, and several autoimmune diseases were common associated diseases. IgG and IgG subclass deficiency should be considered in adult patients presenting with recurrent upper and lower respiratory infections, particularly in those with respiratory allergies or autoimmune diseases.

Two Cases of Malignant Lymphomas in Children with Selective IgA and IgG Subclass Deficiency / 대한소아혈액종양학회지

Selective IgA deficiency is one of the most common primary immunodeficiency. Some patients with IgA deficiency also have deficits in one or more immunoglobulin G subclasses. It has been estimated that up to 25% of patients with certain primary immunodeficiencies will develop tumors, primarily B-cell lymphomas during their lifetime. We hereby present 2 cases of malignant lymphomas, one diffuse large cell lymphoma and another mixed cellularity Hodgkin's disease, respectively, which developed in patients with selective IgA and IgG subclass deficiency.

A case of intravenous immunoglobulin therapy in severe aspirin - sensitive asthma patient combined with IgG1 and IgG3 subclass deficiency / 천식및알레르기

Common complications in a patient with IgG subclass deficiency include recurrent respiratory infections and concomitant inflammatory lung disease. The most effective therapy in these patients is the administration of intravenous immunoglobulin. The authors report a case of severe aspirin-sensitive asthma and recurrent pneumonia with combined IgG1, and IgG3 subclass deficiency in a 19-year-old man. The patient was treated with 0.4g/kg at monthly intervals for 6 months, and is still receiving 0.2g/kg every 2 weeks at our clinic. After the replacement of intravenous immunoglobulin, the patient has clinically improved.

Immunologic Considerations in the Pathogenesis of Chronic and Recurrent Sinusitis in Children

PURPOSE: Although the chronic sinusitis is one of the most common and troublesome respiratory diseases in children, the pathogenesis still remains unclear. It is suggested that many of the immunologic factors including allergic conditions may contribute the nasal inflammatory changes. This study was designed to evaluate and demonstrate the possible role of various immunologic factors on the pathogenesis of chronic sinusitis in children. METHODS: During the 6 months study period from March to August, 1995, 33 children with chronic and recurrent clinical symptoms of sinusitis were evaluated. History taking, physical examinatin, paranasal radiologic examination, total IgE, allergen-specific IgE antibodies, serum IgA, IgG subclasses and T cell subsets were analysed in most of the children. RESULTS: The results were as follows; 1) The value of total serum IgE was increased in 19 cases(63.3% of the total). 2) All children in this study shows normal serum IgA levels. 3) In ten of 31 children(74.1%) with chronic sinusitis, serum concentrations of IgG2 were lower than geometric mean value. There was a decreased concentration of IgG1 in 3 cases(21.4%), IgG3 in 4 cases(28.6%), and IgG4 in 2 cases(14.3%). 4) The ratio of T4 to T8 was less than 2 in 23 cases(82.1%) out of 28 cases and reversed in 1 case. 5) Decreased serum concentration of IgG2 was more prevalent in cases with normal serum IgE levels rather than the cases with high serum IgE levels. 6) There was no correlation between the toral serum IgE levels and the ratio of T4 to T8 7) In the case with reversed T4 to T8 ratio, all the IgG subclasses are decreased except IgG3. 8) Chronic cough was the most common clinical manifestations in this study and postnasal drip, purulent nasal discharge, nasal stuffiness, fever and allergic shiner were noted in order. 9) Many of the children in this study have an allergic diseases, such as allergic rhinitis(48.5%), asthma(45.5%), and atopic dermatitis(33.3%). 10) PNS radiographs show diffuse opacification or mucosal thickening in all of the patients. CONCLUSIONS: In this study, we suggested that complex immunologic reactions including IgE-mediated allergic reaction, IgG subclasses deficiencies and cellular immunity are involved in the pathogenesis of chronic and recurrent sinusitis.

Asma y deficiencia de subclases de IgG / Asthma and IgG subclasses deficiency

Se estudiaron 45 pacientes asmáticos adultos de difícil manejo, de más de 5 años de evolución, 37 de ellos esteroide dependientes y 8 no dependientes, con asma alérgica o intrínseca y algunos con infecciones respiratorias recurrentes de predominio viral. Por nefelometría se midieron los niveles séricos de las Igs G, M y A, y por ELISA se determinó la IgE total. Se encontraron 4 pacientes con deficiencia de IgG total, en el grupo de los esteroide dependientes. Mediante ELISA tlpo sandwich y con anticuerpos monoclonales específicos para las subclases de IgG se investigaron los niveles séricos de IgG1, 2, 3 y 4. En el 55.6 por ceinto de los enfermos se encontraron una O más deficiencias de subclases. No hubo diferencias significativas entre los grupos esteroide y no esteroide dependientes, ni entre los asmáticos alérgicos e intrínsecos, ni entre los con infección recurrente o sin ella. Predominó la deficiencia de IgG1; en total el 46.7 por ciento de los pacientes tenían deficiencia aislada o combinada de IgG1, el 31.1 por ciento de IgG2, el 24.4por ciento de IgG3 y el 17.8 por ciento de Igd4. La alta incidencia de deficiencia de subclases podría deberse a la acción de los esteroides o a una alteración en la regulación de la síntesis de Igs producida por un defecto Inmune primario. Esta deficiencia sería la responsable del comportamiento agresivo de la enfermedad

We studied 45 adult asthmatic patients with difficult to care disease and who had more than five years of evolution; they suffered from elther allergic or intrinsic asthma and some had experienced recurrent respiratory tract infections. predominantly of viral etiology. Serum levels of IgA, IgG and IgM were measured by nephelometry and total lgE was determined by an Enzyme-Linked immunosorbent Assay (ELISA). Total lgG deficiency was found in four steroid. dependent patients. Serum levels of IgG subclasses 1 to 4 were measured by means of a sandwich-like ELISA with specific monoclonal antibodies. One or more subclass deficiencies were present In 55.6% of the patients. Significant differences were not found between the following groups: steroid and nonsteroid dependent patients; allergic or intrinsic, asthma; and individuals with or without history of infection. IgG 1 deficiency was the most commonly found: It was present in 46.7% of the patients, either as an isolated disorder or combined with alteration of other subclasses. Deficiency of other subclasses was present in the following proportions: 31.1% for IgG2; 24.4% for IgG3 and 17.8 for IgG4. The high incidence of subclass deficiency may be due to steroid action or to primary Immune defects leading to disorders of IgG synthesis. Such situation might be responsible for the aggressive behavior of the disease