IgG4 Levels (igg4 + level)

Distribution by Scientific Domains


Selected Abstracts


IgG4-related disease: Historical overview and pathology of hematological disorders

PATHOLOGY INTERNATIONAL, Issue 4 2010
Yasuharu Sato
IgG4-related diseases comprise a recently recognized systemic syndrome characterized by mass-forming lesions in mainly exocrine tissue that consist of lymphoplasmacytic infiltrates and sclerosis. There are numerous IgG4-positive plasma cells in the affected tissues, and the serum IgG4 level is increased in these patients. The present study describes the history, autoimmune pancreatitis (AIP), IgG4-related lymphadenopathy and lymphomagenesis based upon ocular adnexal IgG4-related disease. Lymphoplasmacytic sclerosing pancreatitis, a prototypal histological type of AIP, is now recognized as a systemic IgG4-related disease. Lymph node lesions can be subdivided into at least five histological subtypes, and systemic IgG4-related lymphadenopathy should be distinguished from multicentric Castleman's disease. Interleukin-6 and CRP levels are abnormally high in multicentric Castleman's disease, but are normal in the majority of systemic IgG4-related lymphadenopathy. Ocular adnexal IgG4-related disease frequently involves bilateral lacrimal glands swelling, and obliterative phlebitis is rare. Moreover, some malignant lymphomas, especially mucosa-associated lymphoid tissue lymphoma, arise from ocular adnexal IgG4-related disease. In addition, IgG4-producing lymphoma also exists. [source]


IGG4-RELATED SCLEROSING LYMPHOPLASMACYTIC PANCREATITIS AND CHOLANGITIS MIMICKING CARCINOMA OF PANCREAS AND KLATSKIN TUMOUR

ANZ JOURNAL OF SURGERY, Issue 4 2008
Moon-Tong Cheung
Background: Autoimmune sclerosing pancreatitis is a well-known disease entity for years, particularly recognizing the difficulty in distinguishing it from malignancy. Immunohistochemical study showed that immunoglobulin IgG4 staining was positive in plasma cells of some autoimmune pancreatitis or cholangitis. The term ,autoimmune sclerosing pancreatocholangitis' was used as it was believed that they belonged to a range of disease involving both pancreas and biliary tree. It may also be part of a systemic fibro-inflammatory disease. Patients and Methods: All the patients suffering from immunoglobulin G4 (IgG4)-related pancreatitis and cholangitis from May 2003 to September 2006 in Queen Elizabeth Hospital, Hong Kong were retrospectively studied. Results: A total of five patients with clinical diagnosis of IgG4-related autoimmune pancreatitis or cholangitis were analysed. All presented with jaundice or abdominal pain, mimicking carcinoma. Two patients had major resection, two patients were diagnosed by intraoperative biopsy and one was based on serum IgG4 level. Conclusion: With the growing awareness of this relatively recently characterized clinical entity and its similar presentation to pancreatic carcinoma or bile duct cholangiocarcinoma, it is important for autoimmune sclerosing pancreatocholangitis to be included in the differential diagnosis of pancreaticobiliary disease. The management strategy has shown to be modified , from major resection to intraoperative biopsy and to the assay of serum IgG4 level without the necessity of histology confirmation. [source]


Salivary IgA and IgG subclasses in oral mucosal diseases

ORAL DISEASES, Issue 6 2002
S Sistig
OBJECTIVE:,It was hypothesized that serum levels of immunoglobulins may play a role in the pathogenesis of oral mucosal diseases, or reflect clinical changes in these conditions, but little is known about the role of salivary immunoglobulins in the pathogenesis of these diseases. The aim of this study was to investigate possible alterations in salivary immunoglobulin A (IgA) and IgG subclasses in patients with oral mucosal inflammatory diseases. SUBJECTS and METHODS:,Levels of IgG1, IgG2, IgG3 and IgG4 were determined by enzyme-linked immunosorbent assay (ELISA), and IgA1 and IgA2 by radial immunodiffusion in the resting whole saliva of 31 patients with acute recurrent aphthous ulceration (RAU) (and followed in remission), 11 patients with chronic hyperplastic candidal infection (CHC), 12 patients with Sjögren's syndrome (SS), six patients with oral lichen planus (OLP), and 18 healthy volunteers using the normal saliva as a comparison point for all. RESULTS:,IgG and IgA subclasses were increased in OLP. In CHC all IgG subclasses were increased while IgA1 was decreased, IgG1, IgG3 and IgG4 levels were increased in SS, while all IgG subclasses as well as IgA2 were increased in acute RAU in comparison with healthy controls. No differences in any immunoglobulin subclasses between major and minor acute RAU were found. In remission, IgG1 and IgG4 returned to normal values while IgG2, IgG3, and IgA2 remained increased in patients with RAU. CONCLUSION:,Salivary immunoglobulin subclasses vary in different oral mucosal conditions and may play a role in oral mucosal inflammatory diseases and/or reflect clinical changes in these conditions. [source]


Casein-specific immunoglobulins in cow's milk allergic patient subgroups reveal a shift to IgA dominance in tolerant patients

PEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2007
Gaynour B. G. Sletten
Differences in casein-specific immunoglobulin (Ig) G-subclass and IgA serum levels between reactive and tolerant patients may hint at the immunopathogenesis during tolerance development in cow's milk allergy (CMA). , -, ,- and , -casein-specific IgG1, IgG4, IgE and IgA serum levels were compared in clinically reactive and tolerized IgE-mediated (n = 15) and non-IgE-mediated (n = 14) CMA with delayed gastrointestinal symptoms, using enzyme-linked immunosorbent assay (ELISA) and immunoblot techniques. The median anti-casein IgE levels in clinically reactive IgE-mediated CMA patients (n = 9) were 140- to 180-fold higher than in tolerized patients (n = 6) and 160- to 200-fold higher than in controls (n = 10). Median , -, ,- and , -casein-specific IgG1 and IgG4 levels were nine- to 60-fold higher in reactive patients and five- to 60-fold in tolerized patients. Clinical tolerance in IgE-mediated CMA was thus associated with decreased casein-specific IgE, IgG4 and IgG1, whereas serum IgA anti- , -, , - and , -casein remained practically unaltered. Tolerized cow's milk protein (CMP)-sensitive atopic dermatitis had, in particular, decreased , -casein-specific IgG1 levels, compared with clinically reactive patients. The ELISA levels to immunoblot correlation profile for the , -, , - and , -casein-specific IgE suggested that the IgE-mediated CMA patients predominantly reacted to tertiary , - and , -casein epitopes whereas the IgE in non-IgE-mediated patients reacted to linearized , -, , - and , -casein epitopes. Clinical tolerance in non-IgE-mediated CMA patients (n = 9) was associated with a four- to 10-fold decrease in casein-specific IgE levels, accompanied by a five- to eightfold decrease in IgG1 and five- to 60-fold decrease in IgG4 levels, whereas casein-specific IgA levels remained unaltered. Thus, tolerance in both patient groups was characterized by a generalized decreased humoral immune response to caseins, which induced a functional shift to IgA dominance. [source]


Immunoglobulin subgroups in children with febrile seizures

PEDIATRICS INTERNATIONAL, Issue 1 2001
Hüsey, n Çaksen
Background: The aim of the present study was to determine whether or not there was a role for immunoglobulin (Ig) or IgG subgroups in the pathogenesis of febrile seizures (FS). Methods: Serum levels of IgA, total IgG, IgM, IgE, IgG1, IgG2, IgG3 and IgG4 were measured in 34 children with FS and in 37 healthy children used as a control group. Both patients and controls were divided into two groups according to age (group I, 6,24 months; group II, 25,72 months). Results: Compared with controls, mean IgG4 levels in patients were found to be decreased in both groups I and II (group I: 95~14 vs 57~5, respectively, P=0.01; group II: 178.5~38.5 vs 65.1~24.5, respectively, P<0.01), while mean IgG2 levels were found to be decreased only in group II patients (170~16 vs 103~22; P<0.05). Conclusions: The results of the present study suggest that Ig subclass deficiencies may be responsible for the infections connected with FS or that they may be related to the pathogenesis of FS in some children. [source]


Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease

ARTHRITIS & RHEUMATISM, Issue 6 2010
Arezou Khosroshahi
Objective Patients with IgG4-related systemic disease (IgG4-RSD) frequently show an incomplete response to treatment with glucocorticoids and traditional disease-modifying antirheumatic drugs (DMARDs). B lymphocyte depletion is a therapeutic strategy known to be effective for pemphigus vulgaris, an autoimmune condition mediated by IgG4 autoantibodies. This study was performed to assess the clinical and serologic responses to B lymphocyte depletion therapy with rituximab in patients with IgG4-RSD. Methods Four patients with IgG4-RSD were treated with 2 intravenous doses (1 gram each) of rituximab. Clinical improvement was assessed by monitoring the tapering/discontinuation of prednisone and DMARDs, and by measuring the serum concentrations of B lymphocytes, immunoglobulins, and IgG subclasses before and after therapy. Results Clinical features of IgG4-RSD in these 4 patients included autoimmune pancreatitis, sclerosing cholangitis, lymphoplasmacytic aortitis, salivary gland involvement, orbital pseudotumor, and lacrimal gland enlargement. The 3 patients with elevated serum IgG and IgG4 levels at baseline had a mean IgG concentration of 2,003 mg/dl (normal range 600,1,500 mg/dl) and a mean IgG4 concentration of 2,160 mg/dl (normal range 8,140 mg/dl). Among these patients, the serum IgG4 concentrations declined by a mean of 65% within 2 months of rituximab administration. All 4 patients demonstrated striking clinical improvement within 1 month of the initiation of rituximab therapy, and tapering or discontinuation of their treatment with prednisone and DMARDs was achieved in all 4 patients. A decrease in IgG concentration was observed for the IgG4 subclass only. Conclusion Treatment with rituximab led to prompt clinical and serologic improvement in these patients with refractory IgG4-RSD, and is a viable treatment option for this condition. The decline in serum IgG4 concentrations was substantially steeper than that of the autoantibody concentrations in immune-mediated conditions in which rituximab is effective, such as in rheumatoid arthritis. In addition, the reduction in IgG-subclass levels appeared to be specific for IgG4. The swift improvement of IgG4-RSD suggests that rituximab achieves its effects in IgG4-RSD by depleting the pool of B lymphocytes that replenish short-lived IgG4-secreting plasma cells. [source]


IgG4-related systemic disease and lymphoplasmacytic aortitis

ARTHRITIS & RHEUMATISM, Issue 10 2009
John H. Stone
We describe herein a patient who developed a dissection of the ascending aorta in the setting of IgG4-related systemic disease, linking IgG4-related systemic disease with a newly-recognized subset of noninfectious aortitis. At the time of aortic surgery, a transmural lymphoplasmacytic infiltrate was detected in the patient's aorta, with a principal focus of inflammation within the media. Immunohistochemical studies demonstrated that >50% of the plasma cells in the lesion stained for IgG4. By in situ hybridization, the plasma cells showed polytypic staining for kappa and lambda light chains, consistent with a polyclonal plasma cell infiltrate. Serologic evaluation revealed that the patient's IgG4 levels were elevated nearly 10-fold. Four years before aortic surgery, the patient had undergone a mediastinal lymph node biopsy. Reexamination of the lymph node revealed features consistent with IgG4-related systemic disease, which had not been recognized at the time of the original biopsy. Glucocorticoid therapy for the IgG4-related systemic disease yielded a prompt response. Recognition that IgG4-related systemic disease can involve the ascending as well as the descending abdominal aorta indicates the need for a change in the way idiopathic aortitis is regarded. This case offers new potential considerations for short- and long-term management of noninfectious aortitis, because of the frequent good response of IgG4-related systemic disease to glucocorticoid treatment without additional therapy. Treatment of the aortitis may prevent progression of the IgG4-related systemic disease to involvement of other organs. IgG4-related systemic disease should be considered in all patients with aortitis judged to be of unknown etiology. [source]


Time course of serum inhibitory activity for facilitated allergen,IgE binding during bee venom immunotherapy in children

CLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2009
E-M Varga
Summary Background Immunotherapy for bee venom allergy is effective and provides long-term protection. Venom-specific IgG4 levels are increased but with no correlation with clinical improvement. Following grass pollen immunotherapy, elevation of antigen-specific IgG4 is accompanied by increases in IgG-dependent serum inhibitory activity for IgE-facilitated binding of allergen,IgE complexes to B cells. As this ,functional' assay of inhibitory antibodies may be more predictive of clinical efficacy, we investigated the time course of serum inhibitory activity for IgE-facilitated antigen binding during venom immunotherapy (VIT) in children and following 2 years of VIT withdrawal. Methods Ten bee venom-allergic children (mean age: 9.3 years; m/f, 7/3) with moderate to severe allergic reactions to bee stings received VIT. A separate group of seven children (mean age: 14 years; m/f, 5/2) were investigated 2 years after VIT withdrawal. Ten age- and gender-matched children served as non-allergic controls. Allergen-specific serum IgG4 and IgE levels were measured by ELISA at baseline, after 2 years of VIT and 2 years after VIT withdrawal. Serum inhibitory activity was assessed using the facilitated-allergen binding (FAB) assay. Results Sera obtained during VIT significantly inhibited allergen,IgE binding to B-cells (pre-treatment=104±23%; 2 years=46±15%; P<0.001) when compared with sera obtained after treatment withdrawal and sera from normal controls. In parallel to FAB inhibition during VIT, significantly higher IgG4 levels were noted after immunotherapy (pre-treatment=8.6±2.3 AU; 2 years=26.7±3.5 AU; P<0.001) compared with those observed after withdrawal and in the controls. In contrast, progressively lower IgE concentrations were observed compared with pre-treatment (44±7 AU) in sera obtained after 2 years of VIT (25±5 AU; P<0.01) and 2 years following the withdrawal of VIT (10±3 AU; P<0.05). Conclusions In contrast to grass pollen immunotherapy, the persistent decline in venom-specific IgE levels, rather than serum inhibitory activity for FAB, may be more relevant for long-term clinical efficacy of VIT. [source]


Higher immunoglobulin E antibody levels to recombinant Fel d 1 in cat-allergic children with asthma compared with rhinoconjunctivitis

CLINICAL & EXPERIMENTAL ALLERGY, Issue 8 2008
H. Grönlund
Summary Background Current diagnosis of allergy and asthma to cat is confirmed using cat dander extract (CDE). We have previously engineered a recombinant major cat allergen, rFel d 1, with properties identical to the natural molecule. Objective The aim of the study was to evaluate IgE and IgG4 antibodies to rFel d 1 among sera from cat-allergic children and adults suffering from asthma and/or rhinoconjunctivitis (RC) in populations from Sweden and Austria. Methods Cat-allergic children and adults from Sweden (n=27 and 31, respectively) and Austria (n=41 and 41) with RC and/or asthma were selected. Sera were tested for IgE and IgG4 antibodies to CDE and rFel d 1 by CAP, and IgE to rFel d 1 by ELISA. Healthy subjects and non-cat-allergic patients (n=75) were included as controls. Results There was a high correlation between IgE responses to rFel d 1 and CDE among the 140 patients (rs=0.85, P<0.001); however, measured levels to rFel d 1 were on average 30% higher (P<0.0001). Ninety-eight percent of patients and none of the controls showed IgE to rFel d 1 and there was a threefold increased risk of asthma for half of the children with the highest IgE levels [odds ratio 3.23; 95% confidence interval (CI), 1.19,8.79] by ELISA. IgE responses to rFel d 1 among children with asthma were higher (median 19.4 kU/L) compared with children with RC (median 6.6 kU/L, P<0.05) and adults with asthma (median 3.0 kU/L, P<0.01). Furthermore, children with asthma displayed higher IgG4 levels than the asthmatic adults. Conclusion A single recombinant molecule, rFel d 1, is at least as sensitive for in vitro diagnostics of cat allergy as the current extract-based test. Elevated IgE antibody levels to Fel d 1 are suggested to be a risk factor for asthma in cat-allergic children. [source]


Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin-specific immunoglobulin responses are ubiquitous, but peanut-specific immunoglobulin responses are up-regulated in peanut allergy

CLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2007
S. S. Tay
Summary Background The clinical significance of food-specific IgG subclasses in food allergy and tolerance remains unclear. Specific IgG titres are often reported in non-standardized units, which do not allow comparisons between studies or allergens. Objective To quantify, in absolute units, ovalbumin (OVA)- and peanut-specific IgG levels in children with peanut or egg allergy (active or resolved) and in non-allergic controls. Methods Children aged 1,15 years were recruited. Peanut allergy was diagnosed by convincing history and a 95% predictive level of specific IgE; egg allergy or resolution was confirmed by oral challenge. Serum IgG, IgG1 and IgG4 levels (,g/mL) to OVA and peanut extract were quantified by ELISA. Results OVA- and peanut-specific IgG was detected in all subjects. In non-allergic controls (n=18), OVA-specific IgG levels were significantly higher than peanut-specific IgG (median ,g/mL IgG=15.9 vs. 2.2, IgG1=1.3 vs. 0.6, IgG4=7.9 vs. 0.7; P<0.01). There were no differences in OVA-specific IgG, IgG1 and IgG4 between egg-allergic (n=40), egg-resolved (n=22) and control (n=18) subjects. In contrast, peanut-specific IgG (median ,g/mL IgG=17.0, IgG1=3.3, IgG4=5.2) were significantly higher in peanut-allergic subjects (n=59) compared with controls and with non-peanut-sensitized but egg-allergic subjects (n=26). Overall, the range of IgG4 was greater than IgG1, and IgG4 was the dominant subclass in >60% of all subjects. Conclusion OVA-specific IgG levels of egg-allergic, egg-resolved or control groups are not distinguishable. Higher peanut-specific IgG levels are associated with clinical allergy, but the range of IgG titres of the allergic and control groups overlapped. Hence, OVA and peanut-specific IgG measurements do not appear to be of diagnostic value. Strong IgG responses to OVA may be a normal physiological response to a protein frequently ingested from infancy, whereas up-regulated IgG responses in peanut allergy may be indicative of a dysregulated immune response to peanut allergens. [source]