Tissue IgG4 Levels Research Articles

Otologic Manifestations of IgG4-Related Disease: Literature Review and Report of Two Cases

Background: IgG4-related disease (IgG4-RD) is an inflammatory process. The literature on IgG4-RD is rather limited, with mastoid involvement being uncommon. In such cases, presentation may mimic other middle ear and mastoid cavity pathologies. Objective: To summarize findings of patients with IgG4-RD involving the mastoid. Methods: Description of two new cases and summary of findings with previous reports. Results: Nineteen cases of IgG4-RD with mastoid bone involvement were reported in the literature, the earliest appearing at the beginning of the previous decade. Most frequent symptoms included hearing deterioration, tinnitus and otalgia. In 58% of the cases, the process was restricted to otologic manifestations. In 7 out of 19 cases, tissue IgG4 levels were elevated. In all histopathologic samples taken from the operative sites, a dense lymphoplasmacytic cell infiltration was observed. Following definitive pathological diagnosis, the most common treatment was corticosteroids. Generally, the time from onset to final diagnosis was usually more than six months. The treatment is corticosteroids, followed by immunosuppressive agents such as rituximab, cyclophosphamide, and methotrexate. Conclusions: IgG4-RD involving the mastoid is a challenging condition, both in diagnosis and treatment. Hence, IgG4-RD should be included in the differential diagnosis of middle ear pathologies and include a multi-disciplinary team for treatment.

Clinical value of 18F-FDG PET/CT in IgG4-related disease.

To investigate the clinical value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in IgG4-related disease (IgG4-RD). Seventy two patients diagnosed with IgG4-RD who underwent PET/CT were included. Correlations between clinical variables and PET/CT findings were analyzed by Spearman's correlation test. Conventional radiology was compared to PET/CT to evaluate detection discrepancies. The detection ability of insidious organ involvement by PET/CT at disease onset was investigated. The utility value of PET/CT for the 2019 ACR/EULAR classification criteria was analyzed with the multivariate logistic analysis and ROC curve. SUVmax of main involved organ was positively correlated with IgG4-RD Responder Index (IgG4-RD RI), serum and tissue IgG4 levels and IgG4/IgG ratio, serum eosinophils counts and number of involved organs, while negatively correlated with serum IgM levels. PET/CT was superior in detecting organ/tissue involvements including prostate, gastrointestinal tract and lung compared with conventional imaging. For patients with pancreato-hepato-biliary or head-neck involvements at onset, PET/CT showed superiority in detecting insidious lesions. Multivariate analysis showed that disease duration, multiple-organ involvement, SUVmax of main involved organ and mean SUVmax of all involved organs were significantly associated with the fulfillment of the 2019 ACR/EULAR classification criteria. ROC curves indicated that the cut-off value for SUVmax of main involved organ and mean SUVmax of all involved organs for fulfillment of the 2019 ACR/EULAR classification criteria for IgG4-RD were 4.1 and 3.5, respectively. 18F-FDG PET/CT has potential capacity to monitor disease activity, evaluate organ involvements and assist in the classification criteria in IgG4-RD.

Clinical and Biological Markers Predict the Efficacy of Glucocorticoid- and Macrolide-Based Postoperative Therapy in Patients With Chronic Rhinosinusitis.

Although subsequent anti-inflammatory treatments are indispensable for patients with chronic rhinosinusitis (CRS) undergoing sinus surgery, few studies have explored the factors influencing the efficacy of postoperative anti-inflammatory treatment. We aimed to develop prediction models for the response to glucocorticoid- and macrolide-based postoperative therapy in CRS patients. We performed a post-hoc analysis of our previous study comparing the efficacy of fluticasone propionate and clarithromycin in the postoperative treatment of CRS patients. Clinical characteristics and treatment outcome information were collected. In addition, diseased sinonasal mucosal tissues obtained during surgery were processed for Bio-Plex analysis of protein levels of 34 biomarkers. Classification trees were built to predict refractory CRS based on clinical characteristics and biological markers for patients treated with fluticasone propionate or clarithromycin. A random forest algorithm was used to confirm the discriminating factors that formed the classification trees. One year after surgery, 22.7% of the patients (17/75) treated with fluticasone propionate, and 24.3% of those (18/74) treated with clarithromycin were diagnosed with refractory CRS. Nasal tissue IL-8 and IgG3 levels and headache VAS scores in the fluticasone propionate group, and nasal tissue IgG4 levels and overall burden of symptoms VAS scores in the clarithromycin group, were identified as discriminating factors forming the classification tree to predict refractory CRS. The overall predictive accuracy of the model was 89.3% and 87.8% for fluticasone propionate- and clarithromycin-based postsurgical treatment, respectively. Classification trees built using clinical and biological parameters could be helpful in identifying patients with poor response to fluticasone propionate- and clarithromycin-based postoperative treatment.

The diagnostic value of serum IgG4 for the diagnosis of IgG4-related disease: and is that so great?

IgG4-related disease (IgG4-RD) is a systemic immune mediated condition that is characterized by the formation of tumor-like fibroinflamma-tory foci in different organs and by the elevation of serum and tissue IgG4 levels in the majority of patients. The pathogenesis of the disease, including the role of IgG4, has not been established exactly. Serum and tissue IgG4 hypersecretion is a nonspecific sign and occurs in many rheumatic, infectious, and malignant diseases. Objective : to determine the range of nosological entities associated with the increase in serum IgG4 levels, as well as the frequency and nature of this increase in patients with IgG4-RD. Patients and methods . The results of all serum IgG4 measurements carried out in the Laboratory of Immunology and Molecular Biology of Rheumatic Diseases, V.A. Nasonova Research Institute of Rheumatology, in 2017—2018 were analyzed. Serum IgG4 parameters were separately estimated in 52 patients with verified IgG4-RD according to the universal diagnostic criteria proposed by H. Umehara et al (2011). Results and discussion . In 2017—2018, a total of247patients were tested for serum IgG4 levels. The latter were elevated in 76 (30.8%) patients, but only 28 (36.8%) were diagnosed as having IgG4-RD. Along with IgG4-RD, antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) were characterized by increased serum IgG4 levels. The highest median IgG4 level was found in patients with a verified diagnosis of IgG4-RD: 6.31 vs 3.2, 3.22, and 2.69 g/L in ANCA-associated vasculitis, RA, and SLE, respectively. In 52 patients with IgG4-RD, the IgG4 level >1.35 g/L was found in 88% of cases. The median serum IgG4 level was 3.45 g/L (2.1; 11.4). The highest level was observed in patients with generalized lymphadenopathy and in those with IgG4-related sialoadenitis and dacryoadenitis (Mikulicz disease). The serum IgG4 level was positively correlated with the number of affected organs (Spearman's correlation coefficient, 0.39; p=0.0056, Student's t-test). All the patients showed a tendency towards decreasing serum IgG4 levels during treatment regardless of its clinical response; however, the levels returned to normal only in 73% after 12 months of treatment. Conclusion . The increased serum and tissue IgG4 concentration is not specific, but at the moment it is the only disease marker available in clinical practice. To correctly interpret the diagnosis, it is necessary to assess the entire set of clinical manifestations, imaging data, and morpholopathological findings.

Esophageal IgG4 levels correlate with histopathologic and transcriptomic features in eosinophilic esophagitis.

Recent data associate eosinophilic esophagitis (EoE) with IgG4 rather than IgE, but its significance and function have not been determined. Our aims were to measure esophageal IgG4 levels and to determine functional correlations as assessed by histologic and transcriptome analyses. This case-control study included pediatric subjects with EoE (≥15eosinophils/HPF) and non-EoE controls. Protein lysates were analyzed for IgA, IgM, and IgG1-IgG4 using the Luminex 100 system; IgE was quantified by ELISA. Esophageal biopsies were scored using the EoE histology scoring system. Transcripts were probed by the EoE diagnostic panel, designed to examine the expression of 96 esophageal transcripts. Esophageal IgG subclasses, IgA, and IgM, but not IgE, were increased in subjects with EoE relative to controls. The greatest change between groups was seen in IgG4 (4.2mg/g protein [interquartile range: 1.0-13.1mg/g protein] vs 0.2mg/g protein [0.1-0.9]; P<.0001). Tissue IgG4 levels correlated with esophageal eosinophil counts (P=.0006); histologic grade (P=.0011) and stage (P=.0112) scores; and IL4, IL10, IL13, but not TGFB1, expression and had strong associations with a subset of the EoE transcriptome. Esophageal IgG4 transcript expression was increased and correlated with IgG4 protein levels and IL10 expression. These findings extend prior studies on IgG4 in adult EoE to the pediatric population and provide deeper understanding of the potential significance and regulation of IgG4, demonstrating that IgG4 is a relevant feature of the disease; is closely related to esophageal eosinophil levels, type 2 immunity and T regulatory cytokines; and is likely produced locally.

Surgical management of isolated mesenteric autoimmune disease: addressing the spectrum of IgG4-related disease and sclerosing mesenteritis

IgG4-related disease (IgG4-RD) is a rare form of autoimmune sclerosing disease, characterised by elevated serum IgG4 and tissue IgG4 levels, specific histopathological findings, multiorgan involvement and adequate response to glucocorticoid...

Addition of second-line steroid sparing immunosuppressants like mycophenolate mofetil improves outcome of Immunoglobulin G4-related disease (IgG4-RD): a series from a tertiary care teaching hospital in South India.

IgG4-related disease (IgG4-RD) is a systemic fibro-inflammatory disease. This disease may be associated with elevated serum and tissue IgG4 levels. Early treatment prevents fibrosis and organ damage. We retrospectively studied the clinicopathologic correlation and outcome of treatment in IgG4-RD. This single-center retrospective study was done using electronic records of patients subjected to assay of serum IgG4 levels in our laboratory by nephelometry. There were 473 patients with suspected IgG4-RD. Of them, 41 patients fulfilled comprehensive diagnostic criteria for IgG4-RD and 432 had diseases other than IgG4-RD. Clinical and histopathological data including tissue IgG4/IgG ratio, other relevant laboratory findings as well as management data of 41 patients with IgG4-RD were analyzed. There were 29 males and 12 females with mean age of 44.1±2.19years. Thirteen patients had definite, 19 had probable and 9 had possible IgG4-RD. Male predominance, multiple organ involvement and IgG4 responder Index were significantly higher in definite IgG4-RD as compared to probable and possible IgG4-RD. Serum IgG4 level was elevated in 37 patients (90.2%). Glucocorticoids were used in 35 patients (85.4%) and second-line immunosuppressive agent in 23 patients (65.7%). Of the 21 patients on follow-up, 19 (90.7%) had clinical improvement at the first follow-up visit. Nine (90%) out of the ten patients who were assessed by IgG4 responder index, also had shown improved score with treatment. Patients with IgG4-RD in our series showed favorable responses to treatment with glucocorticoids and addition of steroid sparing immunosuppressive agents (mainly mycophenolate mofetil) helped successful tapering of steroids, while maintaining the improvement.

Successful treatment of pediatric IgG4 related systemic disease with mycophenolate mofetil: case report and a review of the pediatric autoimmune pancreatitis literature

Autoimmune pancreatitis is frequently associated with elevated serum and tissue IgG4 levels in the adult population, but there are few reports of pediatric autoimmune pancreatitis, and even fewer reports of IgG4 related systemic disease in a pediatric population. The standard of care treatment in adults is systemic corticosteroids with resolution of symptoms in most cases; however, multiple courses of corticosteroids are occasionally required and some patients require long term corticosteroids. In these instances, steroid sparing disease modify treatments are in demand. We describe a 13-year-old girl with IgG4 related systemic disease who presented with chronic recurrent autoimmune pancreatitis resulting in surgical intervention for obstructive hyperbilirubinemia and chronic corticosteroid treatment. In addition, she developed fibrosing medianstinitis as part of her IgG4 related systemic disease. She was eventually successfully treated with mycophenolate mofetil allowing for discontinuation of corticosteroids. This is the first reported use of mycophenolate mofetil for IgG4 related pancreatitis. Although autoimmune pancreatitis as part of IgG4 related systemic disease is rarely reported in pediatrics, autoimmune pancreatitis is also characterized as idiopathic fibrosing pancreatitis. All pediatric autoimmune pancreatitis cases reported in the world medical literature were identified via a PUBMED search and are reviewed herein. Twelve reports of pediatric autoimmune pancreatitis were identified, most of which were treated with corticosteroids or surgical approaches. Most case reports failed to report IgG4 levels, so it remains unclear how commonly IgG4 related autoimmune pancreatitis occurs during childhood. Increased evaluation of IgG4 levels in patients with autoimmune pancreatitis may shed further light on the association of IgG4 with pancreatitis and the underlying pathophysiology.