Antibody deficiencies with normal IgG in adults with Non-cystic fibrosis bronchiectasis or recurrent pneumonia: Cross-sectional study / Deficiencias Predominantemente de Anticuerpos con niveles normales de IgG en adultos con bronquiectasias no fibrosis quística o neumonía recurrente en Colombia

Abstract Background: Inborn errors of immunity, mainly Predominantly Antibody deficiencies with normal IgG levels are unrecognized in adults with lung diseases such as bronchiectasis or recurrent pneumonia. Objective: To determine IgM, IgA, IgG2 subclass deficiencies, and Specific antibody deficiency (anti-pneumococcal polysaccharide antibodies) in adults with non-cystic fibrosis bronchiectasis or recurrent pneumonia. Methods: Cross-sectional study. Consecutive patients with non-cystic fibrosis bronchiectasis or recurrent pneumonia were recruited in Cali, Colombia. IgG, IgA, IgM, and IgE, IgG2subclass and IgG anti-pneumococcal serum levels were measured. Results: Among the 110 participants enrolled, Antibody deficiencies with normal serum IgG levels were found in 11(10%) cases. IgA deficiency (3 cases), IgM deficiency (2 cases) and IgG2 deficiency (2 cases) were the most frequent primary immunodeficiencies. In addition, IgG2+IgA deficiency, Ataxia-telangiectasia, Hyper-IgE syndrome and Specific Antibody Deficiency(anti-polysaccharides) were found in one case each. Conclusions: Predominantly antibody deficiencies with normal IgG levels are an important etiology of non-cystic fibrosis bronchiectasis and recurrent pneumonia in adults.

Resumen Antecedentes: Los Errores Innatos de la Inmunidad principalmente las Deficiencias Predominantemente de anticuerpos con niveles normales de IgG no se conocen en adultos con enfermedades pulmonares como las bronquiectasias o la neumonía recurrente. Objetivo: Determinar las deficiencias de IgM, IgA y de subclase de IgG2 y la Deficiencia Específica de Anticuerpos (anticuerpos antineumocócicos de polisacáridos) en adultos con Bronquiectasias no Fibrosis Quística (BQnoFQ) o neumonía recurrente. Métodos: Estudio observacional prospectivo. Se reclutaron 110 pacientes consecutivos con BQnoFQ o neumonía recurrente en Cali, Colombia. Se midieron los niveles séricos de IgG, IgA, IgM e IgE, subclase IgG2 y anticuerpos anti-neumococo. Resultados: Se encontraron deficiencias de anticuerpos con niveles normales de IgG en el 10% de los sujetos; Cuatro casos con IgG2 baja, incluido 1 caso de deficiencia de IgG2 + IgA, 1 caso de ataxia-telangiectasia, 3 deficiencias de IgA (IgAD), 2 deficiencias selectiva de IgM (IgMD), 1 síndrome de Hiper-IgE (HIES-AR) y 1 deficiencia específica de anticuerpos. Ocho pacientes fueron diagnosticados con enfermedades relacionadas con la hipogammaglobulinemia IgG. Conclusiones: Las deficiencias predominantemente de anticuerpos con niveles normales de IgG son una etiología importante de BQnoFQ y neumonía recurrente en adultos. Los sujetos con bronquiectasias o neumonía recurrente requieren una evaluación exhaustiva de la respuesta inmune humoral y clínica.

HDL Subclass Analysis in Predicting Metabolic Syndrome in Koreans With High HDL Cholesterol Levels

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is a complex mixture of subclasses with heterogeneous atheroprotective activities. We analyzed HDL-C subclass in relation to cardiovascular risk and metabolic syndrome (MetS) in a population with high HDL-C levels.METHODS: A total of 300 Korean individuals with high HDL-C levels (≥2.331 mmol/L) were enrolled following a comprehensive general medical examination including body composition analysis. HDL3-C levels were measured using the HDL3-EX SEIKEN kit (Randox Ltd., Crumlin, UK) and non-HDL3-C levels were calculated by subtracting HDL3-C levels from total HDL-C levels.RESULTS: HDL3-C levels and HDL3-C proportion had a weak positive correlation with low-density lipoprotein cholesterol (LDL-C) and triglycerides (r=0.21, r=0.25; r=0.26, r=0.34, respectively, all P<0.001); in contrast, non-HDL3-C levels had a weak negative correlation with these parameters (r=−0.17 and r=−0.25, respectively, both P<0.005). HDL3-C levels and HDL3-C proportion were significantly higher in the MetS group (N=8) than in the non-MetS group (0.71 vs 0.63 mmol/L, P=0.001; 29.7 vs 25.8%, P=0.001, respectively); these were the only predictors of MetS among the lipid variables (areas under the curves [AUC]=0.84 and 0.83, respectively, both P=0.001).CONCLUSIONS: In populations with high HDL-C levels, HDL-C subclass may provide a greater amount of information on cardiovascular risk and MetS than HDL-C levels alone.

Utility of immunoglobulin isotypes against LID-1 and NDO-LID for, particularly IgG1, confirming the diagnosis of multibacillary leprosy

BACKGROUND Leprosy remains a health problem in many countries, with difficulties in diagnosis resulting in delayed treatment and more severe disabilities. Antibodies against several Mycobacterium leprae antigens have, however, shown value as diagnostic and/or prognostic markers. OBJECTIVES The objective of this study was to evaluate serum immunoglobulin (Ig) IgM and IgG subclass reactivity against three M. leprae specific antigens: NDO-HSA, a conjugate formed by natural octyl disaccharide bound to human serum albumin; LID-1, the fusion protein product of the ml0405 and ml2331 genes; and NDO-LID, a combination of LID-1 and NDO. METHODS Sera from healthy controls, paucibacillary (PB) and multibacillary (MB) leprosy patients, and their respective household contacts, were evaluated for the presence of antigen-specific IgM, IgG, and IgG subclass antibodies by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of each ELISA were evaluated by receiver operating characteristic (ROC) curve analysis. FINDINGS Our data confirm that serum IgM antibodies against NDO-HSA and IgG antibodies against LID-1, as well as IgG/M antibodies against NDO-LID, are markedly increased in MB patients. For the first time, our data reveal a selective increase in IgG1 and IgG3 antibodies against LID-1 and NDO-LID in MB patients, demonstrating that these antibody isotypes are suitable for differentiation between MB and PB patients. ROC curve analysis indicates an improved capacity for diagnosing MB leprosy patients using the detection of IgG antibodies, particularly the IgG1 isotype, specific to LID-1 and NDO-LID over the performance levels attained with NDO-HSA. CONCLUSIONS Our findings indicate that serological tests based on the detection of antigen-specific IgG1 antibodies are a useful tool to differentiate MB from PB patients, and indicate the enhanced performance of the LID-1 and NDO-LID antigens in the serodiagnosis of leprosy.

Characterization and Biological Activity Analysis of Disulfide Isoforms of Panitumumab / 中国药学杂志

OBJECTIVE: To establish the methods of characterizing and enriching the disulfide isoforms of panitumumab which is a human IgG2 mAb that has been used in the treatment of metastatic colorectal cancer (mCRC) and evaluate the biological activity difference among the isoforms, ie, IgG2-A, IgG2-B, and IgG2-A/B. METHODS: The disulfide isoforms of panitumumab were identified by reversed-phase chromatography. The isoform-A of panitumumab was enriched upon reduction-oxidation treatment when guanidine was added and isoform-B was enriched upon reduction-oxidation treatment without guanidine. Then the molecule structural difference of the isoform-A and isoform-B was analyzed by size-exclusion chromatography. At last, the biological activities of these isoforms were further investigated by cell-killing assay. RESULTS: The component proportions of isoform A, B and A/B in panitumumab were 38%, 32% and 30%, respectively. Under reduction-oxidation conditions, the disulfide isoforms converted to isoform-A when 0.9 mol•L-1 guanidine was used, whereas isoform-B was enriched in the absence of guanidine. And isoform-A was eluted earlier in SECHPLC, suggesting a larger apparent molecular size as compared with isoform-B. Furthermore, the in vitro biological activity measurement showed an increased activity of IgG2-A compared with IgG2-B in inhibiting the growth of DiFi cells. The IC50 s for IgG2-A and IgG2-B were 0.095 46 μg•mL-1 (95% CI 0.079 86 - 0.114 1 μg•mL-1) and 0.372 8 μg•mL-1 (95% CI 0.306 7-0.453 1 μg•mL- 1), respectively. CONCLUSION: The methods for characterizing and enriching the disulfide isoforms are established. Difference in the biological activity between isform-A and isoform-B is observed. The methods will provide technical assist to the process optimization and quality control of panitumumab.

Investigation on serum IgG subclass concentrations in the adult population of Hunan region and their influencing factors / 临床检验杂志

Objective To investigate serum IgG subclass concentrations in the adult population of Hunan region,and the effects of age,gender and lifestyle on them.Methods Serum IgG1,IgG2,IgG3,IgG4 and IgG concentrations from 170 adults making a health examination were detected by the immunonephelometric assay.Results The concentrations (mean or median [P25,P75]) of serum IgG1,IgG2,IgG3,IgG4 and IgG were (7.53 ± 0.14) g/L,3.99 (3.13,5.02) g/L,0.49 (0.30,0.70) g/L,0.53 (0.26,0.93) g/L and 12.2 (10.5,14.1) g/L,respectively.The serum IgG1/IgG,IgG2/IgG,IgG3/IgG and IgG4/IgG were (61.3 ±0.69)％,33.38％ (27.8％,38.8％),3.97％ (2.5％,5.3％) and 4.44％ (2.1％,7.3％),respectively.The serum IgG3 concentrations and IgG3/IgG ratios in female adults were significantly higher than that in male adults (P =0.005 and 0.014).However,there were no significant difference in serum IgG1,IgG2 and IgG4 concentrations and IgG1/IgG,IgG2/IgG and IgG4/IgG ratios between male and female adults.The serum IgG3 concentrations in the 31-40 years old adults were significantly higher than that in the 41-50 years old (P =0.03),while there were no significant difference in serum IgG1,IgG2 and IgG4 concentrations between different age groups.The serum IgG1 concentrations in the adults with heavy smoking were significantly lower than that without smoking (P =0.023),while the serum IgG4/IgG ratios were the opposite (P =0.018).The serum IgG1 and IgG3 concentrations and IgG3/IgG ratios in the adults with midrange or heavy drinking were significantly lower than that without ethanol consumption (P =0.05,0.004 and 0.015,respectively).The serum IgG3 concentrations and IgG3/IgG ratios in the adults with low-risk metabolism syndrome were significantly higher than that with the high-risk (P =0.034 and 0.038).Conclusion Gender and age have the significant effect on serum IgG3 concentration.Heavy smoking may reduce serum IgG1 concentration and increase IgG4/IgG ratio.The decrease of serum IgG1,IgG3 and IgG3/IgG may be related to ethanol consumption.

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.

Renal IgG subclasses in hepatitis-related nephropathy patient with negative plasma hepatitis B antigen / 中国综合临床

Objective To analyze the renal IgG subclasses in special patients whose renal HBsAg and HBcAg are positive, but plasma HBsAg, HBeAg, and HBcAg are negative.Methods Renal IgG subclasses were compared between 14 cases hepatitis-related nephropathy patients(diagnosed by renal biopsy pathology,whose blood hepatitis B antigens were negative) and 18 cases idiopathic membranous nephropathy patients.HBcAg and HBsAg were detected by indirect immunofluorescence assay, IgG, IgG1, 2, 3, 4 were stained by immunofluorescence.Results Renal IgG1-4 deposits were 100％ (14/14), 78.6％ (11/14), 78.6％ (11/14), 100％(14/14) separately in hepatitis B-related nephropathy group, and renal IgG1-4 deposits were 88.9％ (16/18), 5.6％ (1/18), 5.6％ (1/18), and 83.3％ (15/18) in idiopathic membranous nephropathy group.Renal IgG2 and IgG3 deposit more in hepatitis B-related nephropathy group than in idiopathic membranous nephropathy group (78.6％ vs 5.6％ ,78.6％ vs 5.6％;P =0.000) , but no significant difference in IgG1 and IgG4 deposit.Conclusion Renal IgG2 and IgG3 deposit more in hepatitis B-related nephropathy group than in idiopathic membranous nephropathy group, and may help some in diagnosis.

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.

A study on enrichment and purification of core fucose glycosylation and its immunity properties in patients with schizophrenia / 国际检验医学杂志

Objective To establish a platform for enrichment and purification of core fucose glycosylation and analyse its immu‐nity properties .Methods Serum immunoglobulin G(IgG) was seperated and purified by using protein G cross‐linked sepharose ,and core fucose glycosylation components of IgG were enriched and purified by using lens culinaris agglutinin (LCA)affinity chromatog‐raphy ,meanwhile ,the isoforms of LCA‐IgG were determined by using Western blotting .Results The purification rate of serum IgG was 62% and yield rate of LCA‐IgG was 4 .59% .Serum IgG1 ,IgG2 and IgG3 were identified except IgG4 in patients with schizo‐phrenia ,while serum IgG1 ,IgG2 ,IgG3 and IgG4 were all identified in healthy individuals .Conclusion A method for enrichment and purification of core fucose glycosylation in patients with schizophrenia have been successfully established and distribution character‐istics of the LCA‐IgG isoforms have been determined ,which could provide a new insight into immune pathomechanism of schizo‐phrenia .

Anti-PLA2R autoantibodies in serum and IgG subclass deposits on glomeruli in undetermined atypical membranous nephropathy / 中华肾脏病杂志

Objective To investigate the characteristic of autoantibodies of M-type phospholipase A2 receptor (PLA2R) in serum and the glomerular IgG subclass deposits in undetermined atypical membranous nephropathy (MN) patients.Methods From Feb 2004 to Nov 2011,53 cases diagnosed as MN by kidney puneture biopsy in our hospital were included into the study.There were 20 undetermined atypical membranous nephropathy (UAMN),20 idiopathic membranous nephropathy (IMN) and 13 secondary membranous nephropathy (SMN) which were composed of lupus membranous nephropathy (LMN) and HBV related membranous nephropathy (HBV-MN).Clinlical and pathological characteristics were analyzed.The autoantibodies of PLA2R in serum were detected and the glomerular IgG subclass deposits were observed.Results (1) The average age underwent renal biopsy was (37.9±3.8) years of UAMN,(50.1±3.0) years of IMN and (49.5±4.5) years of SMN.The difference in onset average age at disease was significant between UAMN and IMN (P =0.0178).The female/male ratio (F/M) in UAMN,IMN and SMN was 0.8∶ 1,0.7∶1 and 0.6∶ 1(P ＞ 0.05).(2) Compared with SMN,the level of 24-hours urinary protein excretion (3.47 g vs 7.89 g,P =0.023),the ratio of amount urinary protein patients (50.0％ vs 84.6％,P=0.043),the level of serum IgG [(8.40±3.58) g/L vs (10.09±4.69) g/L,P =0.025] and the positive rate of ANA in serum (10.0％ vs 53.8％,P =0.006) in UAMN were all much lower.There were no significant statistical differences in serum albumin,serum creatinine,eGFR,positive rate of HBsAg,HBeAg or HCV,as well as the ratio of hypo-albuminemia and nephrotic syndrome among the three groups.(3) IF positive rate of IgA,IgM and C1q in UAMN were all significantly higher than that in IMN (P ＜ 0.01).There were no significant differences in IF positive rate of IgA,IgM,C1q,IgG and C3 between UAMN and SMN.The IF strength of IgA,IgG,IgM,C3 and C1q in UAMN showed no significant differences between UAMN and SMN.(4) The serum autoantibodies of PLA2R were only detected in 10 cases of IMN group (50％) with all the other cases negative.This detection rate of serum autoantibodies of PLA2R showed significant statistical differences among the three groups (P ＜ 0.01),but no differences between UAMN and SMN (the detection rate in both groups were 0％).(5) IgG1 deposits was the dominant IgG on the glomeruli in UAMN group (40％),as well as in SMN group (76.9％).IgG4 deposits was the dominant IgG on the glomeruli in IMN group (60％).The positive rate of IgG1 and IgG3 in UAMN showed no significant statistical differences when compared with IMN or SMN.The positive rate of IgG2 in UAMN was significantly lower than in SMN (30.0％ vs 69.2％,P ＜ 0.05).The positive rate of IgG4 in UAMN was significantly lower than in IMN (20％ vs 60％,P ＜ 0.05).The positive rate of IgG1,IgG2 and IgG3 in SMN were all significantly higher than in IMN.Conclusions None of the UAMN group had autoantibodies of PLA2R in serum,and IgG1 deposits was the dominant IgG subclass on the glomeruli which indicated the similarity with the SMN group.At the same time,UAMN was significantly different from SMN in clinical manifestations.

Porphyromonas gingivalis and aggregatibacter actinomycetemcomitans IgG subclass antibody levels as immunological risk indicators of chronic periodontitis: a multilevel approach / Niveles de anticuerpos subclase IgG de porphyromonas gingivalis y aggregatibacter actinomycetemcomitans como indicadores de riesgo inmunológico de periodontitis crónica: un enfoque multinivel

Antibody levels to some periodontal pathogens are associated with enhanced levels of inflammatory markers. The purpose of the current study was to examine the relative contribution of serum immunoglobulin G (IgG) subclass antibody level factors and local factors on the probing pocket depth in chronic periodontitis. Serum samples were taken from 444 patients diagnosed with moderate and severe periodontitis and 223 control subjects. The IgG subclass antibody titers to Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa) and Tanerella forsythia (Tf) using indirect immunoassay (ELISA) were determined. The relative contribution of patient, tooth and site-associated parameters on the probing pocket depth were evaluated with a hierarchical multilevel model. The results indicated that periodontitis patients had detectable levels of IgG1 and IgG2. High IgG1 and IgG2 antibody levels against Aa occurred in 132 and 142 periodontitis patients, respectively. High IgG1 and IgG2 antibody levels against Pg occurred in 141 and 138, periodontitis patients, respectively, and High IgG1 and IgG2 antibody levels against Tf occurred in 121 and 136 periodontitis patients, respectively. The majority of the variance was attributed to the site level (48 percent). The multilevel analysis associated deeper probing depth with subject factors (serum IgG1 and IgG2 antibody to Pg and Aa), tooth factors (tooth type), and site factors (mesial-distal location and bleeding on probing). Elevated serum IgG1 and IgG2 antibody to Pg and Aa (subject factors) reflects destructive periodontal disease status.

Los niveles de anticuerpos en algunos patógenos periodontales están asociados con mayores niveles de marcadores inflamatorios. El propósito de este estudio fue examinar la contribución relativa de inmunoglobulina sérica G (IgG) factores de nivel de anticuerpos de subclase y factores locales en la profundidad del sondaje en periodontitis crónica. Se tomaron muestras de suero de 444 pacientes con diagnóstico de periodontitis moderada y grave y de 223 sujetos de control. Se determinaron los títulos de anticuerpos IgG subclase a Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa) y Tanerella forsythia (Tf) mediante inmunoensayo indirecto (ELISA). La contribución relativa de los pacientes, los dientes, y el sitio asociado a los parámetros en la profundidad de sondaje fueron evaluados con un modelo multinivel jerárquico. Los resultados indicaron que los pacientes con periodontitis tenían niveles detectables de IgG1 e IgG2. Altos niveles de anticuerpos IgG1 e IgG2 contra Aa fueron observados en 132 y 142 pacientes con periodontitis, respectivamente. Niveles altos de anticuerpos IgG1 e IgG2 contra Pg fueron detectados en 141 y 138 en pacientes con periodontitis respectivamente, y niveles altos de anticuerpos IgG1 e IgG2 contra Tf se produjeron en 121 y 136 pacientes con periodontitis, respectivamente. La mayor parte de la varianza se atribuyó a nivel de sitio (48 por ciento). El análisis multinivel asociados a profundidad de sondaje con factores relacionados a los sujetos, anticuerpos (suero IgG1 e IgG2 Aa y Pg), factores de los dientes (tipo) y los factores del sitio (localización mesial - distal y sangrado al sondaje). Anticuerpos elevados de suero IgG1 e IgG2 Aa y Pg (factores de los sujetos) reflejan el estado de la enfermedad periodontal destructiva.

Kartagener's syndrome with immunoglobulin G subclass deficiency

Kartagener syndrome is characterized by the triad of situs inversus, bronchiectasis, and chronic paranasal sinusitis. Recurrent sinopulmonary infection, the major determinant for diagnosing immunodeficiency, is the most common clinical manifestation of the disease. A 17-year-old female patient presented with dyspnea, cough, sputum, nasal congestion, and rhinorrhea for more than 5 years. Nasal symptoms and dyspnea had not been controlled by intermittent treatment with mucolytics and antibiotics from primary clinics since 3 months before visiting our clinic. Chest X-ray and computed tomography showed situs inversus, dextrocardia and bronchiectasis. Paranasal sinus series revealed mucosal thickening and haziness on both maxillary sinus. Serum immunoglobulin (Ig) G4 was decreased, but total IgG was within normal range. Under the diagnosis of Kartagener syndrome with IgG4 deficiency, monthly intravenous IgG (IVIG) treatment was performed for 6 months. Her symptoms were well controlled and the frequency of antibiotics use was markedly decreased. We report a patient having the Kartagener syndrome with IgG4 deficiency that was successfully controlled with a 6-month-treatment of IVIG.

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.

Influences of apolipoprotein CII concentrations on high-density lipoprotein subclass distribution / 中国病理生理杂志

AIM: To investigate the influence of serum apolipoprotein (apo) CII concentrations on the distribution of serum high-density lipoprotein (HDL) subclasses. METHODS: Serum HDL subclasses in 247 subjects were determined by two dimensional gel electrophoresis-immunodetection. RESULTS: With the increase in serum apolipoprotein CII levels, age, BMI, the contents of TG, TC, apoB100, apoCII, apoCIII, apoE, preβ_1-HDL, preβ_2-HDL, HDL_3b and HDL_3a increased significantly, but the contents of HDL-C, HDL_(2a) and HDL_(2b) decreased remarkably. The contents of preβ_1-HDL increased with the rise in apoCII and apoA I levels, whereas the content of HDL_(2b) increased with the rise in serum apoA I level in the same apoC II group, but decreased with the increase in serum apolipoprotein CII level in the same apoA I group. With the increase in the ratio of apoCII/ apoCIII, the content of preβ_1-HDL elevated, but the content of HDL_(2b) decreased. The correlation analysis illustrated that the apoCII level was positively correlated with preβ_1-HDL (r=0.186, P<0.01), but inversely correlated with HDL_(2b) (r=-0.149, P<0.05). The apoA I level was positively associated with all HDL subclasses (r in the range of 0.349-0.587, P<0.01). In addition, the apoCIII level was positively correlated with preβ_1-HDL (r=0.184, P<0.01) and preβ_2-HDL (r=0.178, P<0.01), while the apoE level was positively correlated with HDL_(3a) (r=0.040, P<0.05). The apoB100 level was inversely correlated with HDL_(2a) (r=-0.102, P<0.05). CONCLUSION: The particles of HDL show a general shift towards smaller size with the increase in apoCII levels, indicating that the maturation of HDL is abnormal. Whereas the contents of apoA I level correct the effect of apoCII on the distribution profile of HDL subclasses. The ratio of apoCII/apoCIII might also been taken as one of the indexes reflecting the distribution profile of serum HDL subclasses.

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.

Avaliação das Técnicas de ELISA e “Immunoblotting” (IgG e subclasses específicas) no diagnóstico da infecção por Leishmania (Viannia) braziliensis e Leishmania (Leishmania) chagasi em cães / Evaluation of ELISA techniques and \"Immunoblotting\" (IgG subclasses and specific) in the diagnosis of infection with Leishmania (V.) braziliensis and Leishmania (Leishmania) chagasi in dogs

As leishmanioses são enfermidades infecciosas de importância em Saúde Pública. A identificação e retirada de cães infectados é uma medida de controle controversa. A reação de imunofluorescência, utilizada na rotina de diagnóstico, apresenta limitações quanto à sensibilidade e especificidade. Tais limitações podem implicar na manutenção de animais infectados nas áreas endêmicas ou na indicação de eutanásias desnecessárias. Por apresentarem elevadas sensibilidade e especificidade, as técnicas de ELISA e “immunoblotting” deveriam ser melhor avaliadas. A utilização de antígeno homólogo e a detecção de subclasses de IgG têm sido relatadas como alternativas para a obtenção de melhores resultados no diagnóstico sorológico. Este estudo teve como objetivo avaliar os parâmetros de acurácia de ELISA IgG e subclasses em soros de cães infectados por Leishmania (Viannia) braziliensis e Leishmania (Leishmania) chagasi (sintomáticos e assintomáticos) e identificar e caracterizar, por “immunoblotting”, bandas de L. (V.) braziliensis e de L. (L.) chagasimais freqüentemente reconhecidas por IgG e subclasses nesses soros. Foram estudadas 162 amostras de soro, sendo 34 de cães com leishmaniose tegumentar americana (LTA), 37 com leishmaniose visceral americana (LVA) (sintomáticos e assintomáticos), 4 com infecção mista (Leishmania (Viannia) braziliensis e Leishmania (Leishmania) chagasi) e 87 amostras de soros controle de cães residentes fora de área endêmica de leishmanioses, sendo 17 cães saudáveis e 70 com doenças que necessitam diagnóstico diferencial com LTA (esporotricose 35) ou com LVA (ehrlichiose 35). As médias de densidade ótica (D.O.) obtidas para detecção de IgG nos soros de cães com LTA ou com LVA foram estatisticamente mais elevadas com os respectivos antígenos homólogos, havendo um equilíbrio da resposta humoral nos animais com infecção mista...

Entretanto, a técnica não permitiu discriminar entre um caso individual de LTA e de LVA. A média de D.O. nos cães com LVA sintomáticos foi mais elevada que nos assintomáticos. IgG1 não revelou resultados promissores, com baixas médias de D.O. e reduzido reconhecimento antigênico nos cães infectados por Leishmania sp., independente da presença de sinais clínicos. As freqüências de detecção de IgG e IgG2, tanto por ELISA quanto por “immunoblotting” foram semelhantes. Não foi observada reatividade cruzada com L. (L.) chagasi no “immunoblotting”. Esses resultados sugerem que a utilização de antígenos homólogos para a detecção de IgG por ELISA elevaram a acurácia do teste e que em áreas com sobreposição de transmissão de L. (V.) braziliensis e de L. (L.) chagasi, seria indicado empregar o ELISA com ambos os antígenos. Além disso, o emprego do antígeno de L. (L.) chagasi elevou a especificidade dos testes de ELISA e de “immunoblotting”, permitindo a discriminação entre casos de leishmaniose e controles...

Isotype and IgG Subclass Distribution of Autoantibody Response to Alpha-enolase Protein in Adult Patients with Severe Asthma

PURPOSE: A possible involvement of autoimmune mechanism in the pathogenesis of bronchial asthma has been proposed. Recently, alpha-enolase protein was identified as a major autoantigen recognized by circulating IgG autoantibodies in patients with severe asthma. To evaluate a possible pathogenetic significance of these autoantibodies in severe asthma, isotype (IgG, IgA, IgM, and IgE) and IgG subclass (IgG1, IgG2, IgG3, and IgG4) distributions of autoantibodies to recombinant human alpha-enolase protein were analyzed. PATIENTS AND METHODS: We examined serum samples from 10 patients with severe asthma and 7 patients with mild-to-moderate asthma, and 5 healthy controls by immunoblot analysis. Severe asthma was defined as patients having at least 1 severe asthmatic exacerbation requiring an emergency department visit or admission in the last year despite continuous typical therapies. RESULTS: IgG1 was the predominant IgG subclass antibody response to alpha-enolase protein in patients with severe asthma. IgG1 autoantibody to alpha-enolase protein was detected in 7 of 10 patients with severe asthma (70%), 1 of 7 patients with mild-to-moderate asthma (14.3%), and none of 5 healthy controls (0%) (chi-square test; p < 0.05). IgA, IgM, and IgE autoantibodies to alpha-enolase protein could not be detected in patients with severe asthma. CONCLUSION: IgG1 subclass was the predominant type of autoantibody response to alpha-enolase protein in patients with severe asthma, suggests a possibility of IgG1 autoantibody- mediated complement activation in the pathogenesis of severe asthma.

Relation between Levels of Immunoglobulin G Subclass and Early Renal Injury in Children with Henoch - Schon- lein Purpura Nephritis / 实用儿科临床杂志

Objective To explore clinical significance of immunoglobulin G(IgG) subclass and the relationship with urine enzyme series and four microalbumen in Henoch - Schonlein purpura nephritis(HSPN). Methods IgG subclass, urine enzyme series, microal-bumen were detected between 28 cases with HSPN and 20 controls. Results The levels of IgG1, IgG2 in HSPN significantly decreased compared with the normal controls. In addition, the levels of IgG, were negative related to microalbumin(MA) and alkaline phosphalase (ALP) in HSPN, P

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.

Serum IgG and IgG subclass in aspirin-sensitive asthma / 천식및알레르기

BACKGROUND AND OBJECTIVES: Immunoglobulin G (IgG) subclass deficiency has been reported in patients with bronchial asthma and is associated with recurrent respiratory tract infections. Aspirin-sensitive asthma (ASA) which affects 10% of adult asthmatics, asthma runs a chronic course with frequent asthma exacerbations, often related to respiratory infections. We performed this study to identify the prevalence of IgG subclass deficiency and evaluate the association between recurrent asthma exacerbations and IgG subclass deficiency in ASA. SUBJECTS AND METHODS: We measured serum levels of IgG and IgG subclass in 26 aspirin- sensitive asthmatic patients (15 steroid used and 11 steroid not used) and 55 healthy controls using nephelometry. Reference values of each IgG subclass was defined as cumulative percentile between 2.5% to 97.5% of controls. RESULTS: Total IgG, IgG1, IgG2 and IgG3 of aspirin-sensitvie asthmatics, were significantly lower than for those of controls (p0.05, respectively). CONCLUSION: Lowered levels of IgG, IgG1, IgG2 and IgG3 were noted in ASA sensitive asthma patients, which might be associated with use of steroid. Further studies will be needed to evaluate their clinical significance.