High Serum Immunoglobulin Research Articles

Spectrums and Prognosis of Kidney Disease in Patients with Ankylosing Spondylitis

Background/Aims: Renal involvement was a common extra-articular manifestation of ankylosing spondylitis (AS). Few reports have investigated the pathological characteristics and renal outcomes of AS patients with kidney disease. The aim of this study was to investigate the pathological spectrums and the renal prognosis of AS patients with kidney disease. Methods: This retrospective and observational study was conducted working on 62 patients (47 males and 15 females) with a diagnosis of AS (ACR, 1984) and renal biopsies between 2008 and 2017. The histopathological findings and associated clinical manifestations were collected, and the renal prognoses of patients with kidney disease were evaluated too. Multivariate binary logistic regression analysis was performed to identify risk factors for the occurrence of IgA nephropathy (IgAN). Results: Renal biopsy revealed that IgAN accounted for a majority (74.2%) of the kidney disease with AS, while membranous nephropathies, minimal change disease, focal segmental glomerulosclerosis, and other lesions accounted for a small minority. Multivariate analysis revealed that serum immunoglobulin A >3.45 g/L and immunoglobulin G >9.06 g/L were risk factors for the occurrence of IgAN. With a median follow-up time of 24.3 months, 28 patients (50.9%) reached complete remission, 9 patients (16.4%) had partial remission, and 1 patient had an eGFR decline >30%. No difference was found in prognosis between IgAN and non-IgAN. Conclusion: IgAN occurred in 76.4% of the kidney disease with AS, and higher serum immunoglobulin A and G increased the risk for the occurrence of IgAN. The renal prognosis of kidney disease in AS was good.

Autoimmune Hepatitis With Severe Hypergammaglobulinemia and Eosinophilia in a Child

We report here a 7-year-old Afghan girl with autoimmune hepatitis (AIH). Because she showed hepatic dysfunction with markedly high serum immunoglobulin G (IgG) (5,234 mg/dL) and eosinophilia (absolute eosinophil counts: 9,547/µL) at onset, we had difficulty in diagnosing this case by differentiating from various possible diseases. After wedge biopsy of the liver which histologically showed chronic hepatitis pattern as well as high titers (1:640) of anti-nuclear antibody with other negative autoantibodies, the patient was eventually diagnosed as AIH type 1 and successfully managed with a combination of prednisolone (PSL), azathioprine and ursodeoxycholic acid (UDCA), followed by a maintenance therapy with PSL, cyclosporine and UDCA. Int J Clin Pediatr. 2020;9(2):50-54 doi: https://doi.org/10.14740/ijcp372

A Case of Ruptured Immunoglobulin G4-Related Periaortitis.

An 80-year-old man had high serum immunoglobulin G4 (IgG4) concentration and fibrous thickening of the soft tissue mass surrounding the region from the abdominal aorta to the bilateral iliac arteries, suggestive of IgG4-related periaortitis. He presented to our emergency department with sudden-onset abdominal pain and lumbago. Computed tomography revealed a ruptured abdominal aorta. He was a poor candidate for open surgery due to his hostile abdomen. Therefore, endovascular aneurysm repair was performed. No consensus about the surgical indication for IgG4-related arterial disease has been reached yet. We believe that a novel indicator is needed for this disease.

Repeated Vaginal Exposures to the Common Cosmetic and Household Preservative Methylisothiazolinone Induce Persistent, Mast Cell-Dependent Genital Pain in ND4 Mice.

A history of allergies doubles the risk of vulvodynia—a chronic pain condition of unknown etiology often accompanied by increases in numbers of vulvar mast cells. We previously established the biological plausibility of this relationship in mouse models where repeated exposures to the allergens oxazolone or dinitrofluorobenzene on the labiar skin or inside the vaginal canal of ND4 Swiss Webster outbred mice led to persistent tactile sensitivity and local increases in mast cells. In these models, depletion of mast cells alleviated pain. While exposure to cleaning chemicals has been connected to elevated vulvodynia risk, no single agent has been linked to adverse outcomes. We sensitized female mice to methylisothiazolinone (MI)—a biocide preservative ubiquitous in cosmetics and cleaners—dissolved in saline on their flanks, and subsequently challenged them with MI or saline for ten consecutive days in the vaginal canal. MI-challenged mice developed persistent tactile sensitivity, increased vaginal mast cells and eosinophils, and had higher serum Immunoglobulin E. Therapeutic and preventive intra-vaginal administration of Δ9-tetrahydrocannabinol reduced mast cell accumulation and tactile sensitivity. MI is known to cause skin and airway irritation in humans, and here we provide the first pre-clinical evidence that repeated MI exposures can also provoke allergy-driven genital pain.

Pulmonary artery pseudoaneurysm causing massive hemoptysis in hyperimmunoglobulin E syndrome: a case report

BackgroundHyperimmunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder defined by high serum immunoglobulin E titers that is associated with recurrent respiratory infections, formation of pneumoatoceles, recurrent skin abscesses, and characteristic dental and skeletal abnormalities.Case presentationWe report a case of a 56-year-old male with a history of HIES, cavitary mycetomas, and allergic bronchopulmonary aspergillosis who presented with recurrent massive hemoptysis. Bronchial artery angiography and bronchoscopy failed to identify active hemorrhage, and two embolizations of the bronchial artery did not resolve the bleeding. Subsequently, selective pulmonary artery angiography was conducted that demonstrated a subsegmental pulmonary artery branch pseudoaneurysm with extravasation into an adjacent lung cavity. This was treated successfully with transcatheter embolization.ConclusionsTo our knowledge, this is the first case reported of pulmonary artery pseudoaneurysm in HIES in the medical literature. Pulmonary artery pseudoaneurysm should be considered in the differential diagnosis in patients with HIES and massive hemoptysis.

Immunoglobulin G4-Related Coronary Periarteritis With Multiple Intracoronary Images

A 58-year-old man who had been diagnosed with bilateral hilar lymphadenopathy and high serum immunoglobulin G4 (IgG4) level was treated as having possible IgG4-related disease (IgG4-RD). Computed tomography revealed abdominal aortic aneurysm. He was given 40 mg/day of oral prednisolone (PSL) for 2

84-Year-Old Male With Obstructive Jaundice Due to IGG-4 Related Sclerosing Cholangitis

Patient is 83 y.o. male with history of DM type 2, hypertension, CAD, was hospitalized with 2 weeks of progressive fatigue and jaundice, bilirubin 11.2 mg/dL; ALT 227 U/L and AST 150 U/L, alkaline phosphatase 842 U/L and normal CA 19-9 U/mL. CT abdomen showed intra and extrahepatic biliary ductal dilatation with abrupt tapering of the common bile duct (CBD) at the level of the pancreatic head, prominent pancreas. ERCP revealed normal pancreatic duct and distal CBD stricture; pancreatic and biliary stents were placed, biopsies of the stricture were non diagnostic. Repeat ERCP 1 month later showed resolution of distal biliary stricture and formation of new strictures in the CBD, left hepatic duct and intrahepatic bile ducts. CA 19-9 was mildly elevated at 44 U/mL. Strictures were dilated and additional stricture biopsies were obtained. Pathology showed mild increase in numbers of IgG4 plasma cells up to 28 IgG4 positive plasma cells per 400 per high power field (HPF). Liver biopsy showed a dense peribiliary plasma cell-rich inflammatory infiltrate in a setting of fibrotic background, variable presence of eosinophils within the infiltrate, absence of prominent lymphocytic infiltration of the biliary epithelium, canalicular cholestasis without significant ductular proliferation; mild sinusoidal lymphoplasmacytic infiltrate. An immunohistochemical stain for IgG4 showed numerous peribiliary plasma cells (over 70 IgG4-expressing plasma cells per 400x microscopic field), compatible with IgG4-associated cholangitis. (Figure 1 and 2) IgG4 level was 214.2 mg/dL. Patient was started on 40 mg daily of prednisone which lead to resolution of symptoms and normalization of liver tests. Discussion: IgG4-related disease is an increasingly recognized immune-mediated condition which is comprised of a collection of disorders that share particular pathologic, serologic, and clinical features. It has slight predominance in middle age and older males as we see in our case. IgG4 — related sclerosing cholangitis ((IgG4-SC) may present as a distal or proximal-type disease with or without autoimmune pancreatitis. In some cases diagnosis may be challenging. It can mimic primary sclerosing cholangitis and cholangiocarcinoma due to elevation in CA 19-9 level. High serum immunoglobulin G4 (IgG4 level) is an important feature. Liver biopsy can aid in the prompt diagnosis. High level of suspicion and awareness of this condition can lead to prompt diagnosis and correct treatment.1251_A.tif Figure 1: No Caption available.1251_B.tif Figure 2: No Caption available.

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.

Prevalence of Eimeria Species in Sheep with A Special Reference to Vaccinated Pregnant Ewes for Maternal Immunity for the First Time

Sheep coccidiosis is an infection of economic and medical importance and have been observed in almost all alive sheep rearing in the world. Examination of 928 sheep fecal samples from different localities in Kaloubia Governorate for detection of Eimeria infection revealed a prevalence rate of 72.5% (n= 673/928). The identified Eimeria species oocysts were Eimeria candelas (78.3%), E. granulosa (63%), E. ovinoidalis (41%), E. parva (31.5%), E. pallida (22.1%), E. intricata (6.8%), E. faurei (6.2%) and E. ahasta (4.9%). The prevalence rate was high in females (76.3%) as compared to males (68.3%). The incidence of infection peaked in winter (83.1%) followed by spring (80.8%), while the lowest rate was in summer (61.0%). High prevalence rate was recorded in ages > 6 months (90.8%), followed by 6-12months (73.6%), while the lowest rate was in sheep over 1 year of age (55.6%). Single infection was recorded in 26.6% of infected sheep. Double infection rate was in 29.7% while mixed infection rate was in 43.7%. With regard to breeds, Rahmany and Osemy breed showed the highest infection rate (80.9% and 73.9%; respectively). On the other hand, Baladi breed showed the lowest infection rate (58.3%). Immunized dam with UV attenuated Eimeria oocysts and their progeny showed a significant increase in both IgG and IgM as compared to non-immunized control group. Biochemical analysis Immunized dams and their progeny showed high level of albumin, Beta and Gamma concentration levels as compared to control dams and their progeny. Conclusion, it could be concluded that Egyptian sheep was infected by 8 species of Eimeria with predominant of Eimeria crandalis and Eimeria granulosa. New born lambs from immunized ewes have high serum immunoglobulin especially IgG compared to those from non-immunized ewes. Recommendation, Immunization of pregnant ewes by two doses UV irradiated Eimeria oocysts one month before parturition to give protection to their progeny.

Case of atopic dermatitis concurrent with idiopathic thrombocytopenic purpura, whose serum thymus and activation‐regulated chemokine level remained undetectable

We report a 9-year-old Japanese female patient with atopic dermatitis associated with idiopathic thrombocytopenic purpura. She demonstrated high serum immunoglobulin (Ig)E and IgE specific to several environmental allergens, but extremely low serum thymus and activation-regulated chemokine (TARC) levels regardless of the disease progression. This case suggests platelets as the main source of serum TARC.

Evaluation of Serum IgA level in nontreated and treated oral squamous cell carcinoma patients

Introduction: Research in early cancer detection has led to discovery of many immunological tumor markers that contribute considerably to supplement the method of diagnosis. High serum immunoglobulin A (IgA) values in patients with cancer have been used as tumor markers. Aims and Objectives: To evaluate and compare the serum IgA levels in nontreated, treated oral squamous cell carcinoma (SCC) patients, and control group. Materials and Methods: A total of 60 patients were included in the study. 20 biopsy confirmed oral SCC patients, who have received no medical treatment, 20 oral SCC patients treated with surgery and/or radiotherapy and 20 normal healthy individuals. Venous blood samples were collected from anterior cubital vein and were delivered to the biochemistry laboratory for the estimation of serum IgA level by nephelometry method. Statistical Analysis Used: Statistical method employed were the Pearson's Chi-square test and One-way analysis of variance (Welch) followed by Games-Howell post-hoc test. Results: We observed significant difference for serum IgA between study subjects in control, nontreated and treated oral SCC patients (P

Characterization of children with recurrent eczema herpeticum and response to treatment with interferon-gamma.

Interferon gamma (IFN-γ) has been used treat severe atopic dermatitis, with equivocal results. Recurrent eczema herpeticum is an underappreciated, therapeutically challenging complication of severe atopic dermatitis. Defects in IFN-γ and other cytokine pathways have been identified in individuals with confirmed eczema herpeticum. This suggests possible benefit from IFN-γ treatment for confirmed eczema herpeticum. The objective of the current study was to evaluate immunologic and microbial parameters and response to IFN-γ treatment in children with confirmed eczema herpeticum. We performed a retrospective review of medical records from eight children with confirmed eczema herpeticum and two children with severe atopic dermatitis without a history of eczema herpeticum treated with subcutaneous IFN-γ. Our cohort of children with confirmed eczema herpeticum was predominantly male and had high total serum immunoglobulin E, evidence of insufficient toll-like receptor responses, and streptococcal skin and pharyngeal colonization. The duration of IFN-γ administration was 4.5-25months. Five children had initial control and then relapse. Three had interval flares. Two had no improvement. Injections were well tolerated, without significant adverse effects. Treatment was associated with an increase in total immunoglobulin E. Poor adherence complicated therapy in five patients. All 10 discontinued IFN-γ for poor perceived efficacy. Children with confirmed eczema herpeticum have evidence of impaired innate and adaptive immunity. IFN-γ did not result in dramatic improvement in either subset. Specific evaluation for IFN-γ production, function, or receptor defects may help predict response.

Characteristics of autoimmune hepatitis in a sample of Egyptian children

BackgroundAutoimmune hepatitis is a rare liver disease that can be presented aggressively in children. Early treatment can control the hyper immune state and save the liver. The aim of the workTo assess clinical manifestations, biochemical features, and response to immunosuppressive drugs in children with AIH. Methods25 children with AIH, based on the International Scoring Criteria of Autoimmune Hepatitis (IAIHG score system), recruited from Pediatric Hepatology clinic, Benha University Hospitals have been analyzed for their clinical, biochemical features, histological profile and their response to treatment. Results25 children were 15 female (60%) and 10 male (40%) their ages ranged from 3 to 15 years old. The main clinical presentation were jaundice (68.0%), abdominal pain (48.0%), acute hepatic-like illness was the first presentation in (32.0%), hepatomegaly (80.0%), splenomegaly (40.0%) lower limb edema (12.0%), and ascites (12.0%). All patients at first presentations had high serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum immunoglobulin G (IgG). According to the autoantibody profile, all children were classified as AIH type 1 as no patient was seropositive for anti-liver kidney microsome antibody (anti-LKM). Prednisone with or without azathioprine was started and complete remission noticed in 13 (52.0%) while 12 (48.0%) had relapses. ConclusionAIH type 1 was the main type of autoimmune hepatitis in children referred to Benha University Hospitals. Females more affected than boys. The combination of prednisone and azathioprine are effective in abating the inflammatory process in most of the cases. Early diagnosis and treatment of AIH had apparently good outcome in children.

Clinical features of IgG4-related periaortitis/periarteritis based on the analysis of 179 patients with IgG4-related disease: a case\u2013control study

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic condition characterized by high serum immunoglobulin G4 (IgG4) concentration and IgG4-bearing plasma cell infiltration in affected organs. Although it has become evident that IgG4-RD also involves the systemic aortic/arterial system, the precise details of this condition remain unclear. The present study sought to clarify the clinical features of IgG4-related periaortitis/periarteritis.MethodsAmong 223 patients with IgG4-RD, 179 (131 male, median onset age 67 years) were recruited for this study. Periaortitis/periarteritis was defined as vessel wall thickness with circumferential enhancement on contrast-enhanced computed tomography.ResultsPeriaortitis/periarteritis was identified in 65 (36.3%; 53 male) of 179 IgG-RD patients. The distribution of IgG4-related periaortitis/periarteritis could be broadly classified into five types, with the most prevalent Type 2 (44.6%) being localized at the infra-renal artery portion of the abdominal aorta and continuing to the iliac arteries. The infra-renal artery region of the abdominal aorta was most frequently involved (>80%) among IgG4-related periaortitis/periarteritis cases. Comparisons of clinical parameters between IgG4-RD patients with and without periaortitis/periarteritis revealed significantly higher propensities for older IgG4-RD onset age and highly active disease state featuring elevated serum IgG, IgG4, circulating immune complex, and soluble interleukin-2 receptor. All patients showed improvement of wall thickening after steroid therapy, although nine patients (20.9%) exhibited worsening of luminal dilatation. The main risk factor for this manifestation was prior luminal dilatation according to multivariate analysis.ConclusionIgG4-related periaortitis/periarteritis predominantly occurred at the infra-renal artery portion of the abdominal aorta, affected older IgG4-RD onset patients, and was prevalent in highly active disease states. As reported previously, the main risk factor for worsening luminal dilation after corticosteroid therapy was the existence of luminal dilation beforehand.

HLA-DRB1 class II alleles in Indian asthmatic population: A candidate gene-environment interaction

IntroductionAsthma is a complex disease with interplay of genes and environment. Genome wide association studies (GWAS) have shown the systematic association of Human leukocyte antigen (HLA) genes with asthma. The objective of present study was to determine the frequency of HLA DRB1 alleles in adult Indian asthmatic and control groups. Material and methodsPolymerase Chain Reaction- sequence-specific typing (PCR-SSP) method was used for HLA genotyping in 98 healthy participants and 72 asthmatics. ResultsThe results revealed that DRB1*03 (OR=2.63, 95% CI=1.32–5.25), DRB1*04 (OR=4.52, 95% CI=1.06–22.02) and DRB1*07 (OR=3.79, 95% CI=1.03–15.10) were positively associated with risk of asthma while DRB1*15 (OR=0.509, 95% CI=0.257–1.01) were negatively associated with risk of asthma in Indian population. Association of low (>150IU/ml) and high (<150IU/ml) total serum immunoglobulin E, tIgE levels and HLA-DRB1 alleles in asthmatics showed no significant association. ConclusionOur results suggest that HLA-DRB1*03, DRB1*04 and DRB1*07 are involved with susceptibility of asthma, while DRB1*15 has protective effect in adult Indian asthmatics.

Hepatic Flavin-Containing Monooxygenase 3 Enzyme Suppressed by Type 1 Allergy-Produced Nitric Oxide.

Flavin-containing monooxygenases (FMOs) are major mammalian non-cytochrome P450 oxidative enzymes. T helper 2 cell-activated allergic diseases produce excess levels of nitric oxide (NO) that modify the functions of proteins. However, it remains unclear whether allergy-induced NO affects the pharmacokinetics of drugs metabolized by FMOs. This study investigated alterations of hepatic microsomal FMO1 and FMO3 activities in type 1 allergic mice and further examined the interaction of FMO1 and FMO3 with allergy-induced NO. Imipramine (IMP; FMO1 substrate) N-oxidation activity was not altered in allergic mice with high serum NO and immunoglobulin E levels. At 7 days after primary sensitization (PS7) or secondary sensitization (SS7), benzydamine (BDZ; FMO1 and FMO3 substrate) N-oxygenation was significantly decreased to 70% of individual controls. The expression levels of FMO1 and FMO3 proteins were not significantly changed in the sensitized mice. Hepatic inducible NO synthase (iNOS) mRNA level increased 5-fold and 15-fold in PS7 and SS7 mice, respectively, and hepatic tumor necrosis factor-α levels were greatly enhanced. When a selective iNOS inhibitor was injected into allergic mice, serum NO levels and BDZ N-oxygenation activity returned to control levels. NO directly suppressed BDZ N-oxygenation, which was probably related to FMO3-dependent metabolism in comparison with IMP N-oxidation. In hepatic microsomes from PS7 and SS7 mice, the suppression of BDZ N-oxygenation was restored by ascorbate. Therefore, type 1 allergic mice had differentially suppressed FMO3-dependent BDZ N-oxygenation. The suppression of FMO3 metabolism related to reversible S-nitrosyl modifications of iNOS-derived NO. NO is expected to alter FMO3-metabolic capacity-limited drug pharmacokinetics in humans.

Risk factors for recurrence of primary biliary cholangitis after liver transplantation in female patients: A Japanese multicenter retrospective study.

Primary biliary cholangitis (PBC) is diagnosed mainly in female individuals, and risk factors for PBC recurrence (rPBC) after liver transplantation (LT) from cadaveric donors have been reported. We conducted a retrospective multicenter study of rPBC in female patients after living‐donor LT (LDLT). A total of 388 female patients undergoing LDLT for end‐stage PBC were enrolled, and the effects of preoperative and operative factors were evaluated. Postoperative factors were evaluated in 312 patients who survived for more than 1 year post‐LDLT. rPBC was defined as abnormal hepatic enzyme levels with typical histological findings in liver biopsies. Fifty‐eight patients (14.9%) developed rPBC with a median of 4.6 (0.8‐14.5) years post‐LT. Cox hazard analysis (P < 0.05) showed that younger recipient age (hazard ratio, 0.95; 95% confidence interval, 0.920‐0.982), shorter operative time (1.00; 0.995‐0.999), higher serum immunoglobulin M level (1.00; 1.001‐1.002), donor sex mismatch (2.45; 1.268‐4.736), human leukocyte antigen B60 (2.56; 1.336‐4.921) and DR8 (1.98; 1.134‐3.448), and initial treatment with cyclosporine A (3.14; 1.602‐6.138) were significantly associated with rPBC. The frequencies of Child‐Turcotte‐Pugh class C (0.46; 0.274‐0.775), the model of end‐stage liver disease score (0.96; 0.914‐0.998), and updated Mayo risk score (1.02; 1.005‐1.033) were significantly lower in rPBC. Posttransplantation use of steroids decreased and that of antimetabolites increased the frequency of rPBC. Conclusion: The timing of LT, recipient conditions, donor characteristics, and immunosuppressive medications may be associated with rPBC in LT recipients. (Hepatology Communications 2017;1:394–405)

Impact of high serum Immunoglobulin E levels on the risk of atherosclerosis in humans.

BackgroundEpidemiological studies show that immunoglobulin E (IgE) levels were higher in subjects with acute coronary events. However, it is unknown if the increased IgE level is a marker of future coronary incidents and whether it may be regarded as a risk factor of an ischemic heart disease.ObjectiveOur aim was to investigate the relationship between IgE levels and some atherosclerotic markers in patients without known atherosclerotic disease.MethodsFifty patients (mean age, 40.96 ± 10.8 years) with high serum IgE levels due to various conditions who did not display evidence of an atherosclerotic disease and 30 healthy control subjects (mean age, 47 ± 8.27 years) were included in the study. Atherosclerotic disease markers including adhesion molecules like vascular cell adhesion molecule-1, intercellular adhesion molecule-1, proinflammatory cytokines such as interleukin-6, endothelin-1, and systemic inflammatory markers such as high sensitivity C-reactive protein were determined by enzyme-linked immunosorbent assay (ELISA). Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurements and carotid intima media thickness using transthoracic Doppler echocardiography.ResultsCFR was significantly lower in the patient group when compared with the control group (p<0.001; 95% confidence interval, -0.79 to-0.20) while carotid media thicknesses were not different between 2 groups. There were no differences in ELISA test results between the 2 groups.ConclusionOur results showed that CFR as an early marker of endothelial dysfunction was significantly lower in patients with high IgE levels. This finding seems to support the role of IgE in the vascular pathology of atherosclerosis.

Genomics, Signaling, and Treatment of Waldenström Macroglobulinemia.

Next-generation sequencing has revealed recurring somatic mutations in Waldenström macroglobulinemia (WM). Commonly recurring mutations include MYD88 (95% to 97%), CXCR4 (30% to 40%), ARID1A (17%), and CD79B (8% to 15%). Diagnostic discrimination of WM from overlapping B-cell malignancies is aided by MYD88 mutation status. Transcription is affected by MYD88 and CXCR4 mutations and includes overexpression of genes involved in VDJ recombination, CXCR4 pathway signaling, and BCL2 family members. Among patients with MYD88 mutations, those with CXCR4 mutations show transcriptional silencing of tumor suppressors associated with acquisition of mutated MYD88. Deletions involving chromosome 6q are common and include genes that modulate nuclear factor-κB, BCL2, BTK, apoptosis, differentiation, and ARID1B. Non-chromosome 6q genes are also frequently deleted and include LYN, a regulator of B-cell receptor signaling. MYD88 and CXCR4 mutations affect WM disease presentation and treatment outcome. Patients with wild-type MYD88 show lower bone marrow disease burden and serum immunoglobulin M levels but show an increased risk of death. Patients with CXCR4 mutations have higher bone marrow disease burden, and those with nonsense CXCR4 mutations have higher serum immunoglobulin M levels and incidence of symptomatic hyperviscosity. Mutated MYD88 triggers BTK, IRAK1/IRAK4, and HCK growth and survival signaling, whereas CXCR4 mutations promote AKT and extracellular regulated kinase-1/2 signaling and drug resistance in the presence of its ligand CXCL12. Ibrutinib is active in patients with WM and is affected by MYD88 and CXCR4 mutation status. Patients with mutated MYD88 and wild-type CXCR4 mutation status exhibit best responses to ibrutinib. Lower response rates and delayed responses to ibrutinib are associated with mutated CXCR4 in patients with WM. MYD88 and CXCR4 mutation status may be helpful in treatment selection for symptomatic patients. Novel therapeutic approaches under investigation include therapeutics targeting MYD88, CXCR4, and BCL2 signaling.

Yüksek Serum İmmünglobulin E Düzeyi Her Zaman Allerjiye Bağlı Değildir: Etiyolojik Değerlendirmede İpuçları

Yüksek Serum İmmünglobulin E Düzeyi Her Zaman Allerjiye Bağlı Değildir: Etiyolojik Değerlendirmede İpuçları