Elevated Serum Immunoglobulin Research Articles

Association Between Caesarean Delivery and Isolated Doses of Formula Feeding in Cow Milk Allergy

F Gil, A Amezqueta, D Martinez. Int Arch Allergy Immunol. 2017;173(3):147–152 To identify perinatal factors that influence the development of cow’s milk (CM) sensitization and allergy. A total of 211 subjects were included in this study. Case subjects were children diagnosed with cow’s milk allergy (CMA) within their first year of life who attended an outpatient pediatric gastroenterology clinic. Control subjects had no history of allergy to CM, regularly tolerated CM, and had no other digestive medical problems. This retrospective case-control study was performed at a single site in Navarra, Spain. Subjects seen in the clinic from 1990 to 2013 were included as case subjects if they had a clinical history of allergic symptoms with the ingestion of CM, elevated serum immunoglobulin E (IgE) levels to CM proteins, and a positive food challenge (although food challenges were not performed if there was a history of anaphylaxis or IgE levels >2.5 killiunits per liter). …

Study of serum IgE levels in childhood asthma in Barabanki region, India

Background: Elevated Serum Immunoglobulin E (IgE) levels are characteristic of most of the allergic diseases including asthma. Most of the asthma patients are allergic to inhaled antigens and chemical antigens, which lead to their sensitization and induce a state of hypersensitivity that is IgE mediated hypersensitivity reaction. The aim of this study was to estimate and compare serum IgE levels in childhood asthmatics and in normal subjects and to obtain the relationship between serum IgE levels and severity of asthma.Methods: A stratified sample of 58 patients within the age group of 5-15 years including 36 male and 22 female asthmatic patients and 58 healthy controls within the same age group were included in this study and classified according to GINA classification 2016. Serum IgE levels were estimated by using ELISA kit.Results: Mean IgE levels ranged from 163.82 IU/mL in normal subjects to 881.81 IU/mL in asthmatics. The mean values of Serum IgE levels in mild, moderate and severe asthmatic children were 625.25 IU/mL, 871.77 IU/mL, 1225.05 IU/mL respectively.Conclusions: High Serum Immunoglobulin E levels were found in childhood asthmatics as compared to normal subjects. Serum IgE levels were found to increase as the severity of asthma increased. The variability in each grade of asthma was very large so we could not find any statistically significant correlation.

Elevated serum immunoglobulin A levels in patients with Clostridium difficile infection are associated with mortality.

The current research investigated immunoglobulin A levels in serum of patients with Clostridium difficile infection. Our main aim was to test whether immunoglobulin A (IgA) levels at the early stage of infection can predict disease severity of C. difficile infection. Fifty-four patients were enrolled in the study. Stool samples were collected and analyzed by PCR for detection of C. difficile. IgA levels were measured in serum samples that were collected from each patient immediately after receiving a positive PCR result. Additionally, data concerning epidemiologic and clinical characteristics of the patients was retrospectively collected from the medical records. Serum IgA levels were not associated with the severity of C. difficile infection. However, a positive correlation between IgA levels and mortality during hospitalization was found. Additionally, IgA levels correlated with C-reactive protein and white blood cell levels. Although we did not find a correlation between IgA levels and C. difficile infection severity, we could associate IgA levels with the severity of general immune response and to complications of the infection, i.e. mortality. We think that this could represent a compensatory mechanism to the damage caused by C. difficile. Considering serum IgA anti-inflammatory functions, it is possible the increase in IgA levels aimed to suppress the more intense inflammatory response in patients who died during hospitalization.

Potential utility of core needle biopsy in the diagnosis of IgG4-related dacryoadenitis and sialadenitis

IgG4-related disease (IgG4-RD) is a systemic immune-mediated disorder characterized by elevated serum immunoglobulin G4 levels, dense lymphoplasmacytic infiltration, and fibrosis of affected organs...

Hilar cholangiocarcinoma associated with immunoglobulin G4-positive plasma cells and elevated serum immunoglobulin G4 levels.

Immunoglobulin G4 (IgG4)‐related disease is a fibroinflammatory systemic disorder with multiorgan involvement. Proximal bile duct involvement results in IgG4‐related sclerosing cholangitis, which is characterized by a lymphoplasmacytic infiltrate with abundant IgG4‐positive plasma cells and fibrosis. Differentiating between cholangiocarcinoma and IgG4‐sclerosing cholangitis can present a diagnostic dilemma. We describe an unusual presentation of a hepatic mass meeting multiple criteria for IgG4‐sclerosing cholangitis but was ultimately found to be cholangiocarcinoma. Several published case reports describe patients with suspected cholangiocarcinoma who are later found to have IgG4‐sclerosing cholangitis, but few reports have demonstrated the reverse. Distinguishing between cholangiocarcinoma and IgG4‐sclerosing cholangitis is challenging, and a high clinical suspicion for cholangiocarcinoma must always be maintained. (Hepatology Communications 2018;2:349‐353)

Kimura's disease

Kimura's disease (KD) is a benign chronic inflammatory disorder attributed to an immune-mediated hypersensitivity which often presents as a tumor-like swelling in the head and neck region with or without lymphadenopathy, associated with hypereosinophilia and elevated serum immunoglobulin E. Most cases have been described predominantly in Chinese and Japanese people. KD has been confused with angiolymphoid hyperplasia with eosinophilia, from which it probably should be distinguished as a separate entity. The course is usually benign except for the potential cosmetic disfigurement. The diagnosis may be suggested by a fine-needle aspirate but is established by a biopsy. A case of KD in a 42-year-old male with recurrent left submandibular swelling is presented together with a brief review of the literature.

Effective “activated PI3Kδ syndrome”–targeted therapy with the PI3Kδ inhibitor leniolisib

AbstractPathogenic gain-of-function variants in the genes encoding phosphoinositide 3-kinase δ (PI3Kδ) lead to accumulation of transitional B cells and senescent T cells, lymphadenopathy, and immune deficiency (activated PI3Kδ syndrome [APDS]). Knowing the genetic etiology of APDS afforded us the opportunity to explore PI3Kδ inhibition as a precision-medicine therapy. Here, we report in vitro and in vivo effects of inhibiting PI3Kδ in APDS. Treatment with leniolisib (CDZ173), a selective PI3Kδ inhibitor, caused dose-dependent suppression of PI3Kδ pathway hyperactivation (measured as phosphorylation of AKT/S6) in cell lines ectopically expressing APDS-causative p110δ variants and in T-cell blasts derived from patients. A clinical trial with 6 APDS patients was conducted as a 12-week, open-label, multisite, within-subject, dose-escalation study of oral leniolisib to assess safety, pharmacokinetics, and effects on lymphoproliferation and immune dysregulation. Oral leniolisib led to a dose-dependent reduction in PI3K/AKT pathway activity assessed ex vivo and improved immune dysregulation. We observed normalization of circulating transitional and naive B cells, reduction in PD-1+CD4+ and senescent CD57+CD4− T cells, and decreases in elevated serum immunoglobulin M and inflammatory markers including interferon γ, tumor necrosis factor, CXCL13, and CXCL10 with leniolisib therapy. After 12 weeks of treatment, all patients showed amelioration of lymphoproliferation with lymph node sizes and spleen volumes reduced by 39% (mean; range, 26%-57%) and 40% (mean; range, 13%-65%), respectively. Thus, leniolisib was well tolerated and improved laboratory and clinical parameters in APDS, supporting the specific inhibition of PI3Kδ as a promising new targeted therapy in APDS and other diseases characterized by overactivation of the PI3Kδ pathway. This trial was registered at www.clinicaltrials.gov as #NCT02435173.

Naturally Acquired Immunity Against Rotavirus Infection and Gastroenteritis in Children: Paired Reanalyses of Birth Cohort Studies.

Observational studies in socioeconomically distinct populations have yielded conflicting conclusions about the strength of naturally acquired immunity against rotavirus gastroenteritis (RVGE), mirroring vaccine underperformance in low-income countries. We revisited birth cohort studies to understand naturally acquired protection against rotavirus infection and RVGE. We reanalyzed data from 200 Mexican and 373 Indian children followed from birth to 2 and 3 years of age, respectively. We reassessed protection against RVGE, decomposing the incidence rate into the rate of rotavirus infection and the risk of RVGE given infection, and tested for serum antibody correlates of protection using regression models. Risk for primary, secondary, and subsequent infections to cause RVGE decreased per log-month of age by 28% (95% confidence interval [CI], 12%-41%), 69% (95% CI, 30%-86%), and 64% (95% CI, -186% to 95%), respectively, in Mexico City, and by 10% (95% CI, -1% to 19%), 51% (95% CI, 41%-59%) and 67% (95% CI, 57%-75%), respectively, in Vellore. Elevated serum immunoglobulin A and immunoglobulin G titers were associated with partial protection against rotavirus infection. Associations between older age and reduced risk for RVGE or moderate-to-severe RVGE given infection persisted after controlling for antibody levels. Dissimilar estimates of protection against RVGE may be due in part to age-related, antibody-independent risk for rotavirus infections to cause RVGE.

IgG4-related disease: a complex under-diagnosed clinical entity.

IgG4-related disease (IgG4-RD) encompasses a spectrum of complex fibro-inflammatory disorders which are often under diagnosed due to unfamiliarity by clinicians. A challenging multitude of clinical manifestations makes the diagnosis cumbersome. The primary clinical feature in IgG4-RD entails a tumor-like presentation coupled with tissue-destructive lesions. Histopathological findings include lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. These findings, in combination with elevated serum immunoglobulin G4 levels, are diagnostic in the setting of single- or multi-organ involvement. A closer understanding of the role of T cells and B cells in the increased production of IgG4 has led to a notion that IgG4 can act as a pathogen, anti-inflammatory agent, or rheumatoid factor. Glucocorticoids are the primary treatment modality; however, relapse is common with prolonged therapy. Alternatively, immunomodulatory agents are being increasingly used as therapy. The aim of this article is to raise awareness of IgG4-RD and review the diagnostic algorithm, as IgG4-RD often mimics a wide array of clinical conditions. In addition, we summarize the pathogenesis and current treatment guidelines of IgG4-RD for clinicians. Awareness and accurate diagnosis are crucial in preventing progression to chronic diseases, thereby diminishing disease-related morbidity and mortality.

English

An experiment was conducted to evaluate fat sources on growth performance, excreta microbiology and noxious gas emissions in broilers. Experimental birds were reared for 5 weeks and divided into two periods: Starter (0 to 3 weeks) and finisher (4 to 5 weeks). A total of 150 one day old Ross 308 broiler chicks were randomly allocated into five treatments with five replications (six birds per replicate) following a completely randomized design. Dietary treatments included FT1 (corn-soybean meal based basal diet with soybean oil), FT2 (corn-soybean meal based basal diet with chicken fat), FT3 (corn-soybean meal based basal diet with tallow), FT4 (corn-soybean meal based basal diet with tallow and lard) and FT5 (corn-soybean meal based basal diet with pork fat/lard). Overall body weight gain and feed intake did not differ due to addition of different dietary fat sources in broiler diet; however, feed conversion ratio was better in FT1 fed group in comparison to other fat groups (P<0.10). The result of the serum immunoglobulins data indicated that, a significant elevation of serum immunoglobulin M (IgM) was observed after dietary addition of FT1, FT2 and FT5 relative to FT4 (P<0.05) Excreta pH did not differ, however, yeast and mold count was highest in FT4 and FT5 relative to FT1 and FT3 (P<0.05). Excreta noxious gas emissions (NH3, H2S and SO2) were lower in FT1 and FT2 in comparison to other fat groups (P<0.05). Overall, the results of the present study suggested that FT1 and FT2 can be prioritized in the diet of broilers with positive influence on body weight gain and feed efficiency, and substantial reduction of noxious gas emissions. Further detail study could be conducted to investigate the single and combination of different dietary fats (with different ratio) on performance and meat quality indices. Key words: Broilers, growth performance, immunity, noxious gas emissions.

Серонегативный аутоиммунный гепатит

Aim of review. To summarize the modern data on the course, diagnostics and treatment approach in seronegative autoimmune hepatitis (SAH). Summary. The number of articles devoted to SAH is quite low at the present time, while all of them are based on the small case series or single cases. Absence of elevated serum γ-globulins, immunoglobulin G and autoantibodies is most commonly seen in acute onset of the disease that is probably caused by delay of humoral immune response of the disease. According to available information one can postulate following: 1) clinical vigilance for SAH, especially at liver diseases with high biochemical activity; 2) performing liver biopsies in all cases of unclear diagnosis; 3) application of standard scoring diagnostic system at autoimmune hepatitis; 4) prescription of immunosuppressive therapy at justified suspicion for SAH (at ruling out of the other causes for liver disease). Conclusion. SAH is a rare type of autoimmune hepatitis which is observed mostly at the acute onset of the disease and require obligatory morphological confirmation.

Phenytoin induced granulomatous interstitial nephritis

Abstract Granulomatous interstitial nephritis (GIN) is a rare histological entity with multiple aetiologies. Infectious causes like tuberculosis predominate in the Indian subcontinent, where as drugs, sarcoidosis and vasculitis are common causes of GIN in the western world. We report a case of a 46 year old man who had been receiving phenytoin for five years, and presented to us with vomitings and oliguria. His evaluation revealed anemia, eosinophilia, azotemia, hypocalcemia and eosinophiluria. He had elevated serum Immunoglobulin E levels. Ultrasound revealed normal kidney size. Renal biopsy done showed non-caseating epitheloid cell granulomas with interstitial infiltration of lymphocytes and eosinophils, indicative of GIN. The common causes of GIN were ruled out and the diagnosis of phenytoin induced GIN was made. Phenytoin was replaced with sodium valporate. Patient received few sessions of haemodialysis and oral prednisolone, following which he showed considerable improvement. GIN is a treatable cause of renal failure and responds to steroids irrespective of the cause. Also medications as a cause of renal disease in patients presenting with acute renal failure must be excluded, even in India for early and correct diagnosis.

Paraclinical findings in Iranian veterans exposed to sulfur mustard gas: A literature review

ObjectiveSulfur mustard (SM) causes various systemic disturbances in human beings. This study aimed to assess paraclinical changes caused by exposure to SM gas in Iranian veterans during the war between Iraq and Iran. MethodsA literature review was carried out in international and national medical databases including ISI, Medline, Scopus, Iranmedex and Irandoc. Both Farsi and English literature were searched. ResultsSearch of the literature yielded 422 medical articles related to SM poisoning. Among them, 30 relevant articles were thoroughly reviewed. The most important reported complications were leukopenia, neutropenia, lymphopenia, eosinophilia, thrombocytopenia, increased bleeding time, positive C-reactive protein (CRP), rheumatoid factor (RF), antinuclear antibody (ANA), decreased T helper cells, natural killer cells, IL6, and IL8 levels, elevation of serum immunoglobulins, decreased levels of T3, T4 and cortisol, increased level of adrenocorticotropic hormone (ACTH), proteinuria, hematuria, and elevated liver enzymes. Also, there were some changes in chest assessments. ConclusionsSM causes profound systemic complications in victims, even years after exposure. The paraclinical changes can be observed in hematology, immune system, biochemistry, hormonal profile and some imaging studies.

Age-Related Cataract Is Associated with Elevated Serum Immunoglobulin E Levels in the South Korean Population: A Cross-Sectional Study.

BackgroundPrevious research has suggested that immunoglobulin E (IgE)-mediated events lead to several chronic diseases. We investigated the association between allergic conditions and age-related cataracts in the South Korean adult population.MethodsA cross-sectional study was performed using data obtained from 1,170 participants aged 40 years or older who were enrolled in the Korean National Health and Nutrition Examination Survey 2010. Multivariable logistic regression was used to examine the relationship between age-related cataracts and allergic conditions, including total serum IgE and allergen-specific serum IgE levels, after adjustment for potential confounders (age, sex, alcohol consumption, smoking, sun exposure, blood pressure, plasma glucose and cholesterol levels, as well as histories of asthma, atopic dermatitis, and rheumatoid arthritis).ResultsAfter adjusting for potential confounders, the odds ratio (OR) for age-related cataract was greater in participants with higher total serum IgE levels (OR = 1.37; P = 0.044). In particular, increased IgE levels were significantly associated with nuclear cataract (OR = 1.42; P = 0.032). However, allergen-specific serum IgE levels did not differ significantly between groups. In the trend analysis, no significant relationship was observed between serum IgE and any type of age-related cataract.ConclusionIncreased total serum IgE level is independently associated with age-related cataracts after adjustment for confounding factors.

Serum immunoglobulin G4 levels and Graves' disease phenotype.

We investigated, at diagnosis, the relationship between serum immunoglobulin G4 levels and the main characteristics of Graves' disease: hyperthyroidism severity, goiter size, presence of active Graves' ophthalmopathy, antithyroid antibodies status, and titer. This prospective study included 80 newly diagnosed Graves' disease patients. The main parameters measured at diagnosis: thyroid-stimulating hormone, free thyroxine, free triiodothyronine, total triiodothyronine, thyroglobulin, antithyroid peroxidase antibodies, anti-thyroglobulin antibodies, thyroid-stimulating hormone receptor antibodies, immunoglobulin G4. In Graves' disease patients, serum immunoglobulin G4 levels were higher than in general population (p = 0.028) and higher in men compared to women (p = 0.002). Only one female patient with intense hypoechoic goiter, high anti-thyroglobulin antibody, and antithyroid peroxidase antibody titers had an elevated serum immunoglobulin G4 level at diagnosis. Patients with immunoglobulin G4 levels above the 75th percentile (>237.52 mg/dl, N = 20) were younger at Graves' ophthalmopathy onset (p < 0.001), had higher antithyroid peroxidase antibody (p = 0.01), and anti-thyroglobulin antibody levels (p = 0.006) and required shorter duration of the first methimazole treatment cycle (p = 0.041) than patients with immunoglobulin G4 below the 75th percentile. At diagnosis, patients with immunoglobulin G4 levels above the 90th percentile (>286.28 mg/dl, N = 8) had lower total triiodothyronine values (p = 0.001) than patients with IgG below the 90th percentile. No significant correlations were found between smoking status (p = 0.58), goiter size (p = 0.50), the presence of ophthalmopathy (p = 0.42) or thyroid-stimulating hormone receptor antibody titers (p = 0.45) and the mean value of immunoglobulin G4 levels at diagnosis. Our data suggest that Graves' disease patients with elevated immunoglobulin G4 levels at diagnosis have a phenotype characterized by higher anti-thyroglobulin antibody and antithyroid peroxidase antibody titers, less severe T3 hyperthyroidism, younger age at ophthalmopathy onset and require a shorter duration of the first methimazole treatment cycle.

58-year-old patient with IgG4-related thoracic aortitis

We report a 58-year-old male with a one-month of fever up to 38.5° C and back pain with reflection in the anterior chest wall. Chest CΤ and magnetic resonance angiography (MRA) revealed thickening of the descending thoracic aorta throughout its length and laboratory tests showed elevated serum immunoglobulin IgG4. The patient was diagnosed with noninfectious IgG4-related thoracic aortitis. He was treated with corticosteroids and Azathioprine, and 3 months later, the patient was asymptomatic with normal inflammatory markers, reduction of IgG4 serum levels and with no findings on imaging with MRA. Cases of IgG4-related thoracic aortitis have been currently described in literature. This rather new entity accounts for around 9% of noninfectious aortitis. As in our case, IgG4-related disease should be considered in any patient found to have aortitis or periaortitis. An early diagnosis and treatment is essential for the survival of such patients.

Elevated serum immunoglobulin E level as a marker for progression of immunoglobulin A nephropathy

BackgroundImmunoglobulin E (IgE) has traditionally been associated with anaphylaxis and atopic disease. Previous studies reported that serum IgE levels are elevated in nephrotic syndrome and suggested IgE levels as a prognostic indicator in glomerular diseases. The aim of this study was to explore the association between serum IgE levels and renal outcome in patients with immunoglobulin A nephropathy (IgAN). MethodsWe included 117 patients with biopsy-proven IgAN. Renal progression was defined if a patient meets one of these criteria: (1) a negative value of delta estimated glomerular filtration rate (mL/min/1.73 m2/mo) or (2) a rise in serum creatinine to an absolute level of ≥1.3 mg/dL (male) or 1.2 mg/dL (female). We defined delta changes in serum creatinine, estimated glomerular filtration rate, and proteinuria as a difference of values during the follow-up period. ResultsA total of 117 patients with IgAN were included. The serum IgE level was significantly high in the renal progressive group compared with the nonprogressive group. Sex and history of gross hematuria were significantly different between the high-IgE group and the low-IgE group. Regression analysis showed that a male sex, initial proteinuria, and change of proteinuria were significantly associated with serum IgE levels. ConclusionThe serum IgE level is potentially associated with disease progression and pathogenesis of IgAN.

A rare case report: Kimura’s disease presenting as bilateral post auricular swellings in a young male

Kimura disease (KD) is a chronic inflammatory disorder with angiolymphatic proliferation, usually affecting young men of Asian race but is rare in other races. The disease is characterized by a triad of painless subcutaneous masses in head and neck region, blood and tissue eosinophilia and moderately elevated serum immunoglobulin E levels.

The Role of Immunoglobulin E in the Pathogenesis of Ketamine Related Cystitis and Ulcerative Interstitial Cystitis: An Immunohistochemical Study

Background: A previous study revealed elevated serum Immunoglobulin E (IgE) in ketamine related cystitis (KC) patients. IgE might participate the pathogenesis of different types of bladder pain syndromes, including KC and interstitial cystitis (IC). Objectives: To investigate the IgE expression in KC and IC bladder tissue. Study Design: Prospective evaluation. Setting: The study was conducted in a tertiary teaching hospital, Hualien Tzu Chi Hospital. Methods: We investigated the bladder IgE with immunofluorescence staining and quantification. The active mast cells were measuring using tryptase. The symptoms and urodynamic study results were recorded. Double immunofluorescence staining of tryptase and IgE was also performed. Sixteen KC patients, 10 ulcerative IC patients, and 20 non-ulcerative IC patients participated. The history and urodynamic parameters were investigated in these patients. The bladder mucosa was biopsied during cystoscopic hydrodistention. Bladder biopsies were also taken from 22 patients with bacterial cystitis and 12 healthy controls. Results: Bladder IgE was positive in 15 (93.8%) KC patients, 9 (90%) ulcerative IC patients, one (5%) non-ulcer IC patient, 8 (36.4%) bacterial cystitis patients, and 2 (16.7%) controls (P &lt; .001). The bladder IgE was greater in the patients with KC than in the others (P &lt; .001). After excluding KC patients, bladder IgE was significantly higher in the patients with ulcerative IC than the others (P &lt; .001). The bladder IgE was significantly correlated with pain on a visual analogue scale (r2 = 0.156, P = .017) and maximum bladder capacity (r2 = 0.423, P &lt; .001). Tryptase expression did not show a significant difference between KC, ulcer IC, and non-ulcer IC (P = 0.222). Double immunofluorescence staining showed co-expression of tryptase and IgE. Conclusions: IgE-mediated inflammation played a significant role in the pathogenesis of KC and ulcerative IC. Key words: Immunoglobulin E, ketamine cystitis, interstitial cystitis

Thymic stromal lymphopoietin in tonsillar follicular dendritic cells correlates with elevated serum immunoglobulin A titer by promoting tonsillar immunoglobulin A class switching in immunoglobulin A nephropathy

Immunoglobulin A (IgA) nephropathy (IgAN) is characterized by high serum IgA levels and IgA deposition in the renal mesangium. Previous studies suggest that elevated serum IgA partly originates from the tonsils. Here, we investigated the mechanisms of IgA production in the tonsils of patients with IgAN. Immunohistochemistry revealed that the number and relative percentage of IgA-bearing cells were significantly increased in the tonsils of IgAN patients. Compared with non-IgAN patients, enhanced IgA class switching and overexpression of thymic stromal lymphopoietin (TSLP), TSLP receptor (TSLPR), activation-induced cytidine deaminase (AID), transforming growth factor-β1 (TGF-β1), Bcell-activating factor of the tumor necrosis factor family (BAFF), and a proliferation-inducing ligand (APRIL) were detected in follicular dendritic cells (FDCs) of tonsillar germinal centers from IgAN patients. Importantly, TSLP correlated with IgA production in isolated FDC-associated clusters. Serum TSLP levels were increased and correlated with IgA overexpression in the tonsils and serum of IgAN patients. These data indicated that TSLP overexpression in tonsillar FDCs may promote IgA class switching in IgAN patients through the cooperative roles of AID, TGF-β1, BAFF, and APRIL. Therefore, interactions between TSLP in FDCs and IgA production in tonsils may be an important mechanism contributing to the pathogenesis of IgAN.