Elevated Serum Immunoglobulin Research Articles

Recurrent staphylococcal abscess in an adolescent with hyperimmunoglobulin E syndrome: A rare presentation

Hyperimmunoglobulin E syndrome (HIES) more commonly referred to as Job’s syndrome, is an infrequent primary immunodeficiency disorder. It can be inherited either by autosomal dominant or recessive mode with each one having distinct varied clinical presentation. The distinguishing clinical features include recurrent infections, dermatitis, and elevated serum immunoglobulin E (IgE) levels. We report a case of an adolescent female who presented with recurrent staphylococcal infection with axillary lymphadenitis, positive family history, and abnormal facial features mainly broad forehead, facial asymmetry, and peripheral blood eosinophilia with significantly high serum IgE levels, suggestive of autosomal dominant HIES.

RECURRENT STAPHYLOCOCCAL ABSCESS IN AN ADOLESCENT WITH HYPERIMMUNOGLOBULIN E SYNDROME: A RARE PRESENTATION

Hyperimmunoglobulin E syndrome (HIES) more commonly referred to as Job’s syndrome, is an infrequent primary immunodeficiency disorder. It can be inherited either by autosomal dominant or recessive mode with each one having distinct varied clinical presentation. The distinguishing clinical features include recurrent infections, dermatitis, and elevated serum immunoglobulin E (IgE) levels. We report a case of an adolescent female who presented with recurrent staphylococcal infection with axillary lymphadenitis, positive family history, and abnormal facial features mainly broad forehead, facial asymmetry, and peripheral blood eosinophilia with significantly high serum IgE levels, suggestive of autosomal dominant HIES.

Mesenchymal Stem Cells and Atopic Dermatitis: A Review.

Mesenchymal stem/stromal cells (MSCs) are stromal-derived non-hematopoietic progenitor cells that reside in and can be expanded from various tissues sources of adult and neonatal origin, such as the bone marrow, umbilical cord, umbilical cord blood, adipose tissue, amniotic fluid, placenta, dental pulp and skin. The discovery of the immunosuppressing action of MSCs on T cells has opened new perspectives for their use as a therapeutic agent for immune-mediated disorders, including allergies. Atopic dermatitis (AD), a chronic and relapsing skin disorder that affects up to 20% of children and up to 3% of adults worldwide, is characterized by pruritic eczematous lesions, impaired cutaneous barrier function, Th2 type immune hyperactivation and, frequently, elevation of serum immunoglobulin E levels. Although, in the dermatology field, the application of MSCs as a therapeutic agent was initiated using the concept of cell replacement for skin defects and wound healing, accumulating evidence have shown that MSC-mediated immunomodulation can be applicable to the treatment of inflammatory/allergic skin disorders. Here we reviewed the pre-clinical and clinical studies and possible biological mechanisms of MSCs as a therapeutic tool for the treatment of atopic dermatitis.

Eosinophilic gastroenteritis with multiple serous membrane effusion as the first sign: a case report and literature review

Multiple serous membrane effusion (MSSE) as the first sign of eosinophilic gastroenteritis is extremely rare, and its clinical features and treatment methods have not been well described. The clinical characteristics, diagnosis, and treatment methods of MSSE in a 44-year-old woman were retrospectively reviewed. Laboratory testing revealed an elevated eosinophil count and serum immunoglobulin E level. The levels of all tumor markers were normal, but the CA125 level in serum and ascitic fluid was significantly increased. Ultrasonography showed a large amount of ascites and a moderate amount of pleural effusion. Echocardiography showed a small amount of pericardial effusion. Chest and abdominal computed tomography showed gastrointestinal wall thickening. Moreover, eosinophilic infiltration was detected in duodenal and rectal biopsy samples that had been collected during endoscopic examination of the upper gastrointestinal system. The patient was treated with 30 mg of prednisolone, and seafood was excluded from her diet for 4 weeks. The prednisolone was tapered over 8 weeks and continued at 5 mg prednisolone daily thereafter. The MSSE and peripheral eosinophilia showed a dramatic response to the steroid treatment. This case indicates that we should be highly aware of MSSE as the first clinical manifestation of eosinophilic gastroenteritis.

Inhibitory Effects of Urtica thunbergiana Ethanol Extract on Atopic Dermatitis-Induced NC/Nga Mice.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease that persists or repeatedly recurs in both childhood and adulthood. Urtica thunbergiana (UT) is an aroma herb with little-known pharmacological effects and anti-inflammatory activities against AD. This study investigated the immunomodulatory efficacy of 50% ethanol-extracted UT in necrosis factor-alpha/interferon-gamma (TNF-α/IFN-γ)-stimulated HaCaT cells in vitro and AD-Biostir-induced NC/Nga mice in vivo. The results showed that UT exhibits a dose-dependent increase in scavenged free radicals, reaching 76.0% ± 1.4% of scavenged 1,1-diphenyl-2-picrylhydrazyl at a concentration of 250 µg/mL. In addition, UT significantly downregulated the mRNA expression of the following pro-inflammatory cytokines and chemokines in TNF-α/IFN-γ-stimulated HaCaT cells: interleukin (IL)-6, IL-8, thymus- and activation-regulated chemokine, macrophage-derived chemokine, and regulated on activation normal T expressed and secreted. UT-treated HaCaT cells showed inhibition of the overexpression of chemokine-regulated signaling molecules, such as nuclear factor-kappa B, inhibitor of kappa B (IκBα), signal transducer and activator of transcription 1, and mitogen-activated protein kinases (MAPKs). UT dietary administration in AD-Biostir-induced NC/Nga mice treated and improved AD-like symptoms, such as scales, epidermal thickening, the dermatitis severity score, high trans-epidermal water loss, reduced skin hydration, increased mast cells, elevated serum immunoglobulin E levels, and an enlarged spleen. UT treatment inhibited the expression of phosphorylated forms of MAPKs, nuclear factor of activated T-cells 1, and regulator IκBα. It also upregulated filaggrin (FLG) production. Therefore, UT shows high anti-AD activity both in vitro and in vivo, and can be a useful anti-AD agent.

Allergic bronchopulmonary aspergillosis with eosinophilic pleural effusion

Allergic bronchopulmonary aspergillosis (ABPA) in a patient without previously diagnosed asthma or cystic fibrosis with pleural effusion at presentation is uncommon and rare. In a high tuberculosis burden country like India, patients with pleural effusion are frequently misdiagnosed as tuberculosis even when there is no bacteriological confirmation. We report a case of a 48-year female who presented with left side pleural effusion not resolving on antitubercular treatment from two months. The pleural fluid was exudative with 20% eosinophils. Investigations revealed peripheral eosinophilia with HRCT thorax showing left lingular and right upper lobe bronchiectasis. Spirometry showed reversible moderate obstruction. Elevated serum immunoglobulin E, Precipitating serum antibodies to Aspergillus fumigatus were positive and the Aspergillus fumigatus immediate skin test yielded a positive reaction. A diagnosis of ABPA associated with eosinophilic pleural effusions was made and the patient was commenced on prednisolone. At review, the patient’s symptoms had considerably improved and her pleural effusions had resolved.

Clinical Significance of Elevated Serum Immunoglobulin G4 Levels in Patients With Rheumatoid Arthritis

Clinical Significance of Elevated Serum Immunoglobulin G4 Levels in Patients With Rheumatoid Arthritis

Evaluation of alterations in serum immunoglobulin concentrations in components of metabolic syndrome, obesity, diabetes, and dyslipidemia

PurposeSerum immunoglobulins (Igs) play a critical role in modulating the immune response by neutralizing pathogens, although little is known about the effect of Igs in development of atherosclerotic cardiovascular disease (ASCVD). Elevated serum Immunoglobulin A (IgA) concentrations have been identified in previous studies in populations with obesity and hypertriglyceridemia, whereas variable concentrations of Immunoglobulin M (IgM) have been observed in the setting of dyslipidemia.MethodsIn this cross-sectional study, investigators examined the association of serum Ig concentrations with components of metabolic syndrome, including obesity, diabetes, and dyslipidemia. All consecutive adult patients aged 18 years or older discharged from two academic teaching hospitals with serum Immunoglobulin G (IgG) concentration measured during their admission were evaluated, with a total of 1809 individuals included and stratified into two groups: those with and those without dyslipidemia.ResultsMean IgG concentration in individuals with and without dyslipidemia was 997 ± 485 mg/dL and 1144 ± 677 mg/dL, respectively (P < 0.0001). After controlling for confounders in the generalized linear model (GLM), the least square mean IgG concentration in individuals with and without dyslipidemia was 1095 and 1239 mg/dL, respectively (P < 0.0001). The mean IgA and IgM concentrations were not significantly different in individuals with and without dyslipidemia both before and after adjusting covariates. After controlling for confounding variables, all three serum Ig concentrations were not significantly different in individuals with and without diabetes.ConclusionDyslipidemia was associated with a lower mean serum IgG concentration. No association with any serum Ig was indentified in individuals with diabetes. Exploration of the association between alterations in serum Igs and metabolic syndrome and the role of alterations of Ig concentrations in disease progression represents an important step in identification of appropriate targeted treatment options for reducing cardiovascular risk.

IgG:IgM Ratios of Liver Plasma Cells Reveal Similar Phenotypes of Primary Biliary Cholangitis With and Without Features of Autoimmune Hepatitis

Within the spectrum of autoimmune liver diseases, there are patients who manifest features of more than one disease, which was previously identified as having overlap syndrome1,2 and is now referred to as variant syndromes. The most common variant syndrome is between primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). Typically, AIH presents with elevated serum immunoglobulin (Ig) G, whereas PBC is associated with elevated serum IgM.3,4 Previous studies have suggested that plasma cells in liver biopsies of AIH patients are predominantly IgG+, whereas in PBC, there is an abundance of IgM+ cells.5,6 We wanted to determine the immunostaining pattern for IgG and IgM of liver plasma cells among Hispanic patients in Los Angeles with features of both PBC-AIH compared with those with PBC or AIH alone.

Metabolomics Distinguishes DOCK8 Deficiency from Atopic Dermatitis: Towards a Biomarker Discovery.

Bi-allelic mutations in the dedicator of cytokinesis 8 (DOCK8) are responsible for a rare autosomal recessive primary combined immunodeficiency syndrome, characterized by atopic dermatitis, elevated serum Immunoglobulin E (IgE) levels, recurrent severe cutaneous viral infections, autoimmunity, and predisposition to malignancy. The molecular link between DOCK8 deficiency and atopic skin inflammation remains unknown. Severe atopic dermatitis (AD) and DOCK8 deficiency share some clinical symptoms, including eczema, eosinophilia, and increased serum IgE levels. Increased serum IgE levels are characteristic of, but not specific to allergic diseases. Herein, we aimed to study the metabolomic profiles of DOCK8-deficient and AD patients for potential disease-specific biomarkers using chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS). Serum samples were collected from DOCK8-deficient (n = 10) and AD (n = 9) patients. Metabolomics profiling using CIL LC-MS was performed on patient samples and compared to unrelated healthy controls (n = 33). Seven metabolites were positively identified, distinguishing DOCK8-deficient from AD patients. Aspartic acid and 3-hydroxyanthranillic acid (3HAA, a tryptophan degradation pathway intermediate) were up-regulated in DOCK8 deficiency, whereas hypotaurine, leucyl-phenylalanine, glycyl-phenylalanine, and guanosine were down-regulated. Hypotaurine, 3-hydroxyanthranillic acid, and glycyl-phenylalanine were identified as potential biomarkers specific to DOCK8 deficiency. Aspartate availability has been recently implicated as a limiting metabolite for tumour growth and 3HAA; furthermore, other tryptophan metabolism pathway-related molecules have been considered as potential novel targets for cancer therapy. Taken together, perturbations in tryptophan degradation and increased availability of aspartate suggest a link of DOCK8 deficiency to oncogenesis. Additionally, perturbations in taurine and dipeptides metabolism suggest altered antixidation and cell signaling states in DOCK8 deficiency. Further studies examining the mechanisms underlying these observations are necessary.

Associations of genotype variants of single nucleotide polymorphism of gene orosomucoid-1-like-protein 3 and atopic diseases at children.

The paper presents data of the firstly conducted in Ukraine own study of associations of the single nucleotide polymorphism (SNP) rs7216389 of orsomucoid-1-like protein 3 gene (ORMDL3) variants’ with atopic diseases in children. Aim: to detect clinical significance of the SNP rs7216389 ORMDL3 in genesis of atopic diseases in children. We examined 153 children aged 3 to 18 years. The main group consisted of 119 children with clinical manifestations of atopic diseases with elevated total serum immunoglobulin E, confirmed by immunofluorescence assay method. The comparison group consisted of 34 children with a non-aggravated individual or family allergic anamnesis in whom there was detected the absence of any clinical syndromes and symptoms of atopic diseases and, mostly, physiological parameters of the serum total immunoglobulin E by immunofluorescence assay method. All the children were genotyped by ORMDL3 gene using polymerase chain reaction in real time with a restricted fragment length polymorphism. The genotype T/T within SNP rs7216389 of ORMDL3 gene significantly prevails among the children with atopic diseases and is associated with an increased incidence risk of seasonal allergic rhinoconjunctivitis (SARC) by 4.11 times (95% CI 1.55; 16.61), perennial allergic rhinitis (PAR) by 5.07 times (95% CI 1.22; 13.90) times and bronchial asthma (BA) by 10.31 times (95% CI 2.50; 42.62). Children with genotype T/T in locus rs7216389 of the ORMDL3 gene are the increased risk group for developing the atopic diseases. Children with genotype C/C in locus rs7216389 of the ORMDL3 gene are the decreased risk group for the development of atopic dermatitis.

51 Eosinophilic Pancreatitis as a Benign Mimicker of Pancreatic Neoplasm: A Systematic Review

INTRODUCTION: Eosinophilic pancreatitis (EP) is a rare form of pancreatitis characterized by diffuse infiltration of the pancreas with eosinophils &amp; elevated serum immunoglobulin E levels. Diagnosis is clinically difficult as endoscopic/radiographic findings often mimic neoplasm, leading to surgical resection. The aim of this review is to chronicle all cases of EP, describe clinical &amp; radiographic presentation &amp; outcome. METHODS: A systematic search was performed with an experienced librarian of PubMed, Embase &amp; Scopus for search terms of “Eosinophilic Pancreatitis” from 1975–4/19/2019. We included all case reports, series, cohorts &amp; randomized studies with diagnosis of EP. Exclusion criteria were articles with other attributable pancreatitis etiology, fetal EP cases, or non-English language. All articles were reviewed by 2 authors. Data was collected on clinical &amp; radiographic findings, comorbidities &amp; outcome. RESULTS: The search yielded 1379 results of which 18 case reports/series of 23 total patients were included. 17/23 (73.9%) were men, mean age 43.6 ± 17.0 years (range 14–74). Most common symptoms at presentation were abdominal pain (18/23), jaundice (9/23), weight loss (6/23), nausea/vomiting (6/23), &amp; recurrent acute pancreatitis (2/23). Comorbidities included Diabetes Mellitus (2/23) &amp; asthma/allergies (4/23). Imaging revealed abnormalities (mass, hypodensity, or enlargement) located in the pancreatic head (13/23), body (2/23) &amp; tail (3/23). A pancreatic mass was most commonly found (11/23), followed by pancreatic enlargement (8/23), pancreatic duct dilatation (5/23) &amp; bile duct dilatation (8/23). 4/23 patients had a pseudocyst; none had necrosis. Pathology showed prominent eosinophilic infiltrate in all cases, with 5/23 having few lymphocytes &amp; 9/23 with diffuse inflammatory infiltrates. 16/23 patients underwent surgical resection with EP diagnosis made post-operatively. 5/23 patients had complications (4/23 resolved with steroids; 1 died from systemic hypereosinophilia with renal failure &amp; chylothorax). CONCLUSION: EP presents more commonly in men in a 3:1 ratio in the 5th decade. EP should be considered in patients with abdominal pain, jaundice, &amp; weight loss with imaging of a pancreatic mass or enlargement, or ductal dilation. EP masquerades as malignancy; however, diagnostic clues to EP include peripheral eosinophilia &amp; presence of diabetes or asthma/allergies. Awareness of EP may allow for potential non-operative diagnosis, avoidance of surgery, &amp; appropriate medical therapy.

2341 An Interesting Case of Drug-Induced Liver Injury Related to Khat

INTRODUCTION: Drug-induced liver injury (DILI) is the most common cause of acute liver failure in the United States (U.S). The United States Drug-Induced Liver Injury Network (DILIN) reported that approximately 15-20% of DILI cases per year could be attributed to herbal and dietary supplements. Khat is a stimulant derived from the leaves of the shrub Catha edulis, which is native to North Yemen and other East African countries. Chewing khat, a drug of abuse, is an established social habit in areas endemic to the shrub. Khat has been associated with clinically relevant acute and chronic liver injury. We present a case of drug induced liver injury related to Khat. CASE DESCRIPTION/METHODS: A 47 year old Yemeni male with no medical history presented with jaundice. He denied prior liver disease, alcohol use or prescription drugs. He reported routine use of Khat. Labwork is shown in Figure 1. MRCP revealed mild hepatosplenomegaly. Viral workup revealed immunity to hepatitis A. The patient presented 3 months later with jaundice and persistently elevated liver enzymes. Abdominal ultrasound was unrevealing. Extensive workup revealed a positive antinuclear antibody 1:320, in homogeneous pattern and an elevated serum immunoglobulin G and was otherwise unrevealing. Liver biopsy revealed mild portal mononuclear infiltration associated with focal interface hepatitis and widespread lobular hepatitis with plasma cell prominence in the infiltrates (Figures 1 and 2). Subsequently the patient was started on a course of Prednisone and Ursodiol with complete resolution of liver injury. DISCUSSION: Liver injury related to Khat typically occurs after years of use and may present acutely with nausea, fatigue, and jaundice or chronically with evidence of portal hypertension. Biochemical injury is typically hepatocellular and liver enzymes may be significantly elevated. Autoantibodies can mimic autoimmune hepatitis. Resolution of liver injury typically occurs with cessation of khat use. Patients may require corticosteroid therapy however the response is typically partial. Liver transplantation due to Khat related liver failure has been reported. Given immigration of individuals from countries endemic to Khat, an extensive history including use of cultural drugs such as Khat and other herbal remedies is critical in making a diagnosis of unexplained liver toxicity. Our case highlights the importance of a complete drug and supplement history and maintaining a high index of suspicion for DILI in the appropriate clinical context.

Abstract P1108: Serum Immunoglobulins are Not Necessary for Experimental Hypertension

The role of B cells and serum immunoglobulins (Ig) in hypertension is unclear. Elevated serum IgG has been observed in some hypertensive patients and in animal models of hypertension. Mice with a severe B cell deficiency due to lack of B cell activating factor receptor (BAFF-R) and mice lacking the cytokine interleukin 21 (IL21) - which is a potent inducer of B cell Ig class switching and high affinity Ig production - are protected from Ang II-induced hypertension and exhibit reduced serum IgG levels. Thus, we sought to determine whether hypertensive IgGs play a causative role in hypertension and end-organ dysfunction. First, we purified serum IgG from normotensive and hypertensive wild type (WT) mice and adoptively transferred equal amounts of IgG by intraperitoneal injection into normotensive recipient mice followed by infusion of a sub-pressor dose of angiotensin II (Ang II) for 2 weeks. Flow cytometric analysis of aortas revealed a modest increase in F4/80+ macrophages (p=0.04) and CD8+ T cells (p=0.02) in mice that received hypertensive IgG. However, there was no difference in endothelial dependent relaxation, renal inflammation, albuminuria, and blood pressure (BP) between the two groups. As an alternative method to investigate the role of class-switched high affinity Igs, we studied mice with genetic deletion of activation-induced deaminase (AID) which is an enzyme necessary for somatic hypermutation (to generate high affinity Igs) and isotype class switching. AID -/- mice exhibit undetectable IgG and higher levels of IgM in serum compared to WT mice. Ang II infusion for 4 weeks revealed no difference in BP, aortic inflammation, renal inflammation, and albuminuria. We also studied mice with deficiency of the IgM heavy chain (uMT). These mice exhibit undetectable levels of all immunoglobulins and are severely deficient in mature B cells. uMT-/- mice are also not protected from hypertension induced by Ang II infusion or deoxycorticosterone acetate (DOCA-salt) treatment. Together, these results demonstrate that while elevated serum immunoglobulins seen in hypertensive animals and humans may represent a biomarker of aberrant immune activation, they are likely not playing a causal role in hypertension pathophysiology.

Distribution characteristics of elevated serum immunoglobulin G4 (IgG4) and its relationship with IgG4-related disease

Objective: To elucidate the distribution characteristics of elevated serum immunoglobulin G4 (IgG4) and its relationship with immunoglobulin G4-related disease (IgG4-RD).Methods: In total, 14 522 unique patients who were tested for serum IgG4 over a 4.5 year period were enrolled. Demographic and serological characteristics of all patients, and the range of diseases and serological characteristics of patients with elevated serum IgG4, were retrospectively analysed. Organ involvement in IgG4-RD patients and the utility of serum immunoglobulin for distinguishing IgG4-RD from non-IgG4-RD were also investigated.Results: Elevated serum IgG4 (> 1.4 g/L) was observed in 1793/14 522 patients (12.3%) and primarily appeared in middle-aged and elderly men. Only 7.3% of patients with elevated serum IgG4 met the diagnostic criteria for IgG4-RD. Elevated serum IgG4 was also found in over 30 types of non-IgG4-RD. Serum IgG4 levels were higher in IgG4-RD patients with multiple-organ involvement and were positively correlated with the number of affected organs. The diagnostic utility of serum IgG4 for IgG4-RD was higher than that of the IgG4/IgG ratio and serum IgG. The optimal serum IgG4 cut-off value for diagnosing IgG4-RD was 2.06 g/L, with a sensitivity of 95.6% and specificity of 94.7%.Conclusions: Elevated serum IgG4 may be present in multiple non-IgG4-RD conditions. However, a high serum IgG4 concentration is of great value for IgG4-RD diagnosis, and there appears to be a positive relationship between serum IgG4 levels and organ involvement in patients with IgG4-RD. Examining the IgG4/IgG ratio and serum IgG does not improve the ability of IgG4-RD diagnosis.

Higher frequency of false-positive serum galactomannan tests among older subjects and the association with elevated serum immunoglobulin G levels.

The incidence of false-positive serum galactomannan (GM) enzyme-linked immunosorbent assay test results has been scarcely examined among older subjects. Additionally, previous studies have highlighted the influence of serum immunoglobulin G (IgG) levels on GM test results. We hypothesised that age-related IgG level elevation might also be associated with false-positive GM test results in older subjects. This study aimed to examine the association between false-positive GM test results and age or serum IgG levels. We investigated the association between false-positive serum GM test results and age in 1071 healthy adult subjects. Then, we validated this association and further explored the correlation with serum IgG levels by retrospectively identifying 700 patients with newly diagnosed haematologic disorders without probable or proven invasive aspergillosis. Healthy subjects with false-positive GM test results were significantly older than those without false-positive results (P<0.001). Among patients with haematologic disorders, IgG myeloma patients showed significantly higher false-positive rates (57/125 [45.6%]) than patients with other haematologic disorders (non-Hodgkin lymphoma: 48/315 [15.2%], myelodysplastic syndrome/aplastic anaemia: 19/141 [13.5%]; both P<0.001) or other types of myeloma (IgA myeloma: 13/60 [21.7%], light chain myeloma: 9/52 [17.3%]; both P<0.01). Furthermore, among non-multiple myeloma patients, advanced age and higher IgG level were also significantly associated with the high frequency of false-positive GM test results. False-positive serum GM test results were frequent among older subjects and patients with elevated serum IgG levels. These results suggested that age- and/or disease-related IgG level elevation could induce this phenomenon.

Sa1831 – Elevated Serum Immunoglobulin G4 Fails to Prognosticate Inflammatory Bowel Disease Outcomes in Primary Sclerosing Cholangitis Patients

Sa1831 – Elevated Serum Immunoglobulin G4 Fails to Prognosticate Inflammatory Bowel Disease Outcomes in Primary Sclerosing Cholangitis Patients

Vanillic acid mitigates the ovalbumin (OVA)-induced asthma in rat model through prevention of airway inflammation

Asthma is a chronic allergic ailment affecting a considerably large population of the world. The aim of this study is to evaluate the ameliorative effects of vanillic acid against ovalbumin (OVA)-induced asthma in rat model. Asthma was induced in Sprague Dawley rats and vanillic acid was orally administered at 25 and 50 mg/kg body weight for 28days. Rats challenged with OVA showed heavy signs of airway inflammation and remodeling similar to chronic asthma, evidenced by the increased differential cell counts and presence of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), along with elevated serum immunoglobulin levels, and the histological results. However, vanillic acid dose-dependently attenuated the manifestation of OVA-induced asthma (p<0.05) through suppression of inflammatory mediators and modulation of immunoglobulin levels in rats. The asthma mitigating properties of vanillic acid might be due to suppression of oxidative stress and prevention of lung airway inflammation.

Hypopituitarism associated with autoimmune pancreatitis: a case report

We herein report the case of a 64-year-old male patient with hypopituitarism associated with autoimmune pancreatitis (AIP). The patient was previously diagnosed with AIP based on the presence of a swollen pancreas, elevated serum immunoglobulin G4, and narrowing of the pancreatic duct by imaging. Magnetic resonance imaging revealed a pituitary stem tumor, and loading test showed a decrease in the function of the anterior lobe suggesting severe failure of growth hormone secretion. Treatment with steroids was effective in reducing the pituitary lesion and improving the function of the anterior lobe. The present case illustrates the importance of pituitary function evaluation before steroid treatment in patients with AIP.

Immunoglobulin G4-related Disease: An Overview.

Immunoglobulin G4-related disease (IgG4-RD) is a recently established systemic disease that is characteristically associated with elevated serum immunoglobulin G4 (IgG4) levels and believed to be caused by autoimmune mechanisms. The clinical features of IgG4-RD include (i) systemic distribution, (ii) imaging findings of swelling, nodules, and/or wall thickening, (iii) high serum IgG4 levels, (iv) abundant IgG4-bearing plasma cell infiltration and fibrosis in affected organs, (v) a favorable response to corticosteroid therapy, and (vi) coexistence with other IgG4-RD manifestations simultaneously or in a metachronous fashion. The concept of IgG4-RD was established based on the culmination of specific discoveries. Specifically, a close association between autoimmune pancreatitis (AIP) and high serum IgG4 levels, massive IgG4-bearing plasma cell infiltration in pancreatic tissues affected by AIP, and systemic other organ involvements in AIP with similar IgG4-bearing plasma cell features opened the gateway from AIP to IgG4-RD. The systemic distribution of IgG4-RD seems to be capable of affecting every organ, causing well-established members including AIP, lacrimal and salivary gland lesions such as Mikulicz’s disease, respiratory diseases, sclerosing cholangitis, kidney diseases, and retroperitoneal fibrosis. IgG4-RD has been diagnosed worldwide, and international collaboration efforts on the disease have led to consensus publications on its nomenclature, pathology findings, and management approach. The algorithms developed for the comprehensive diagnostic criteria for IgG4-RD have remarkably increased detection sensitivity. Oral glucocorticoids are the first-line agents for remission induction, and certain patients with high disease activity may benefit from maintenance therapy afterwards. Originally, IgG4-RD had been considered reversible and to have a good prognosis; however, long-term afflictions sometimes result in transition to advanced-stage conditions with dysfunction and/or complicating malignancy. The immunological abnormalities in IgG4-RD have been reported in both innate and adaptive immune systems; however, it remains unclear whether IgG4 has a pathogenic role or a protective one in disease onset and progression.