Immunoglobulin Levels Research Articles

Effects of Tralokinumab on Clinical and Laboratory Indexes in Atopic Dermatitis: A 24-Week Real-World Study.

Background: Tralokinumab, a monoclonal anti-IL-13 antibody, is approved for treating atopic dermatitis (AD). Real-world data on its effectiveness and safety are limited. Objective: To evaluate the real-world effectiveness and safety of tralokinumab and the transition of laboratory indexes during 24-week treatment for AD patients. Methods: This retrospective study included 104 patients with moderate-to-severe AD treated with tralokinumab 300 mg every 2 weeks after primary 600 mg. Clinical and laboratory indexes were assessed until week 24. Results: At week 24, achievement rates of Eczema Area and Severity Index 75 (EASI 75), EASI 90, and investigator's global assessment 0 out of 1 in systemic therapy-naïve patients, 83.3%, 72.2%, and 44.4%, respectively, were higher than those in systemic therapy-experienced patients, 46.7%, 20.0%, and 6.7%, respectively. Serum levels of immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), and lactate dehydrogenase (LDH) significantly decreased at week 24, whereas neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation response index (SIRI) significantly decreased at week 12 from baseline. Twenty-nine patients (27.9%) experienced mild treatment-emergent adverse events. Conclusions: Tralokinumab treatment showed prosperous therapeutic effects and good tolerability in real-world practice for AD, with higher effectiveness in patients without prior systemic therapy compared with those with prior systemic therapy. Tralokinumab treatment significantly decreased clinical and laboratory indexes, EASI, Peak Pruritus-Numerical Rating Scale, IgE, TARC, LDH, NLR, and SIRI.

Predominantly antibody deficiencies: An important underlying cause of recurrent pneumonia in adults

RATIONALE Limited information exists concerning the causes of recurrent pneumonia in adults, particularly regarding immunodeficiencies or inborn errors of immunity. OBJECTIVES This study aims to evaluate the etiology of recurrent pneumonia in the adult population, with a focus on humoral deficiency and inborn errors of immunity. METHODS A cross-sectional non-interventional study was conducted in Cali, Colombia, from January 2019 to March 2021. Consecutive patients, aged over 14 years but under 65 years, with a history of recurrent pneumonia, were included after providing consent. The study involved a thorough review of their past medical records and radiological studies. All participants underwent complete blood count and serum immunoglobulin level measurements (IgG, IgA, IgM and IgE). Further testing was carried out based on the evaluation of a clinical immunologist. RESULTS Sixty-six (66) individuals, comprising 34 females and 32 males, were enrolled in the study. The onset of symptoms occurred at an average age of 14 years (ranging from 5 to 36 years). The analysis revealed that the most prevalent cause of recurrent pneumonia was inborn errors of immunity (20 cases, 30.3%), followed by idiopathic (9 cases, 13.7%), bronchiectasis (7 cases, 10.7%), primary ciliary dyskinesia (6 cases, 9.0%), asthma (6 cases, 9.0%), and post-tuberculosis complications (5 cases, 7.6%). CONCLUSION Predominantly antibody deficiencies, along with other inborn errors of immunity, were identified as an important factor contributing to recurrent pneumonia in adults. These findings highlight the importance of these conditions as major etiological factors in the context of recurrent pneumonia in the Colombian adult population.

Dietary supplementation of Astragalus flavonoids regulates intestinal immunology and the gut microbiota to improve growth performance and intestinal health in weaned piglets.

Astragali Radix (AS) is a widely used herb in traditional Chinese medicine, with calycosin as its main isoflavonoid. Our previous study discovered that calycosin triggers host defense peptide (HDP) production in IPEC-J2 cells. The aim of this study is to investigate the alleviation effects of AS total flavone and AS calycosin on growth performance, intestinal immunity, and microflora in weaned piglets. Sixty-four piglets were assigned randomly to 4 treatment groups, (1) CON: the basal diet, (2) P-CON: the basal diet plus antibiotics (1 g/kg), (3) AS-TF: the basal diet plus AS total flavone at 60 mg/day per piglet, (4) AS-CA: the basal diet plus AS calycosin at 30 mg/day per piglet. Each treatment consists of 4 replicates with 4 piglets per replicate. Results showed that treatment with AS-TF and AS-CA enhanced average daily growth and average daily feed intake compared to the CON group (P < 0.01), while AS-CA significantly reduced the diarrhea rate (P < 0.05). Both AS-TF and AS-CA significantly increased serum immunoglobulin (Ig) A and IgG levels, with AS-CA further boosting intestinal mucosal secretory IgA levels (P < 0.05). Histological analysis revealed improvements in the morphology of the jejunum and ileum and goblet cell count by AS-TF and AS-CA (P < 0.05). Supplementation of AS-TF and AS-CA promoted the expression of several intestinal HDPs (P < 0.05), and the effect of AS-CA was better than that of AS-TF. In addition, the AS-TF and AS-CA regulated jejunal microbial diversity and composition, with certain differential bacteria genera were showing high correlation with serum cytokines and immunoglobulin levels, suggesting that the intestinal flora affected by AS-TF and AS-CA may contribute to host immunity. Overall, AS CA and AS TF all improved growth performance and health, likely by enhancing nutrition digestibility, serum and intestinal immunity, and intestinal microbial composition. They showed the similar beneficial effect, indicating AS CA appears to be a major compound contributing to the effects of AS TF. This study demonstrated the positive effect of AS flavonoids on weaned piglets and provided a scientific reference for the efficient use of AS products.

Bullous Pemphigoid Severity and Levels of Antibodies to BP180 and BP230

The correlation between serum levels of autoantibodies against bullous pemphigoid (BP) antigens 180 (BP180) and 230 (BP230) with BP disease severity is unclear. To investigate the correlation of anti-BP180 and anti-BP230 immunoglobulin G (IgG) antibody levels with BP disease severity. A search was performed of the Cochrane Central Register of Controlled Trials, Embase, and PubMed databases from their respective inception to April 11, 2024. Studies evaluating the correlation between serum levels of anti-BP180 or anti-BP230 IgG measured using enzyme-linked immunosorbent assay (ELISA) and disease severity assessed per the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) or BP Disease Area Index (BPDAI) were included. No language or geographic restrictions were imposed. Nearly 0.4% of initially identified studies met the selection criteria. One researcher extracted data and another researcher confirmed data. The risk of bias was independently assessed by these researchers using the Quality Assessment of Diagnostic Accuracy Studies 2 tool, with discrepancies resolved by discussion with a third researcher. A random-effects model meta-analysis and a subgroup analysis were conducted based on the ELISA kit manufacturers. Pooled correlation coefficients of antibody levels with ABSIS and BPDAI. In all, 14 studies with 1226 participants were analyzed. The risk of bias of included studies was generally low. The meta-analysis found anti-BP180 autoantibody levels showed moderate correlation with objective BPDAI (r = 0.56; 95% CI, 0.46-0.64) at baseline, strong correlation (r = 0.63; 95% CI, 0.39-0.79) at 3-month follow-up, and moderate correlation (r = 0.53; 95% CI, 0.25-0.72) at 6-month follow-up. Anti-BP180 autoantibody levels also showed moderate correlation (r = 0.52; 95% CI, 0.39-0.62) with ABSIS at baseline, strong correlation (r = 0.62; 95% CI, 0.39-0.79) at 3-month follow-up, and moderate correlation (r = 0.53; 95% CI, 0.25-0.72) at 6-month follow-up. By contrast, anti-BP230 autoantibody levels showed no association with objective BPDAI and ABSIS at diagnosis and follow-up. The subgroup analysis found similar results when using different ELISA kits. The findings of this systematic review and meta-analysis indicated that anti-BP180 autoantibody levels may serve as an adjunctive tool for monitoring BP disease severity and guiding clinical care for patients with BP.

Serum immunoglobulin A levels: Diagnostic utility in alcoholic liver disease and association with liver fibrosis in steatotic liver disease.

The relationship between immunoglobulin A (IgA) levels and chronic liver disease remains poorly understood. The present study evaluated the clinical significance of IgA in 478 new patients who visited the Outpatient Clinic of Nagasaki Harbor Medical Center (Nagasaki, Japan). Serum IgA levels in comparison to liver stiffness (LS), as measured using a FibroScan® device, were evaluated in 358 patients. Furthermore, in 270 patients, the associations between serum IgA levels and body composition were analyzed using computed tomography. The IgA levels of patients in the groups with Child-Pugh classification B and C (CPGBC), alcoholic liver disease (ALD), steatotic liver disease (SLD) or diabetes were higher than the IgA levels of patients in the groups with CPGA, non-ALD, non-SLD or no diabetes, respectively. Logistic regression analysis showed that CPGBC, ALD, high IgG (>1,700 mg/dl), high macrophage galactose-specific lectin-2 binding protein glycosylation isomer (M2BPGi) (>1 cut-off index) and diabetes were contributing factors for high serum IgA level (>410 mg/dl). The ratio of IgA level divided by IgG level was highest in patients with ALD, followed by those with metabolic dysfunction-associated SLD (MASLD) and non-SLD. In SLD, IgA level was associated more with LS than M2BPGi and fibrosis-4 (FIB-4) in multiple regression analysis. In the receiver operating characteristic analysis, IgA level, M2BPG, and FIB-4 had similar area under the curve values for discriminating high LS (>8 kPa) from low LS (≤8 kPa) in SLD. IgA levels were also associated with visceral fat, and this association was only found in women. In conclusion, elevated IgA is an indicator of liver fibrosis that also reflects the presence of diabetes and an increased visceral fat level. Therefore, IgA is considered a useful marker of liver disease severity in the current era of increased SLD.

Persistently Low IgG2 Levels in a Subset of Patients Following Hematopoietic Cell Transplantation.

Infectious diseases remain a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Secondary hypogammaglobulinemia is a risk factor for infectious diseases. Total immunoglobulin G (IgG) levels and the history of infectious diseases are an integral part of determining the indication for immunoglobulin replacement therapy. The clinical significance of IgG2 levels is not well established. Guidelines recommend using pathogen-specific IgG to evaluate patients with potential secondary immunodeficiency. However, it is difficult in practice to perform such testing. IgG2 may correlate well with pathogen-specific IgG but the clinical significance of IgG2 is not well established. To assess the prevalence of low IgG2 levels with normal IgG after HCT, we cross-sectionally measured the levels of several immunoglobulins, including IgG, IgA, IgM, and IgG2, after HCT, and we assessed the correlation between them. Among 121 patients who underwent cross-sectional measurements of IgG, IgA, IgM, and IgG2 levels after HCT, 114 had normal IgG2 levels (normal IgG2 group, ≥ 100mg/dL) and 7 had low IgG2 levels (low IgG2 group, < 100mg/dL). These 7 patients were allogeneic HCT recipients. All 7 patients with low IgG2 had cGVHD and 4/7 patients had normal total IgG levels. IgG2 levels may be low even in patients with normal IgG levels years after allogeneic HCT. Therefore, our study suggests that when patients develop infectious diseases, especially multiple episodes, it is recommended to measure IgG2 levels to exclude the possibility of secondary hypogammaglobulinemia after allogeneic HCT.

Vaccine response was higher in formula-fed infants compared to breastfed but not affected by lactoferrin or iron in a randomised controlled trial.

To examine how reduced iron content and added bovine lactoferrin in infant formula affect the antibody response following routine immunisation. In this randomised controlled trial, 180 Swedish formula-fed infants received, from 6 weeks to 6 months of age, a 2 mg/L iron formula with (n = 72) or without (n = 72) bovine lactoferrin, or a control formula with 8 mg/L iron and no lactoferrin (n = 36). Another 72 infants were recruited as a breastfed reference. Serum immunoglobulin G (IgG) levels against Haemophilus influenzae type b (Hib), diphtheria and tetanus were assessed at four, six and 12 months of age. With an equal gender distribution, 180 + 72 term infants were included with a mean age of 7.0 ± 0.7 weeks. At 12 months, infants fed low iron formula showed a significantly higher geometric mean Hib IgG (1.40 μg/mL [1.07-1.83]) compared to the control formula infants (0.67 μg/mL [0.42-1.07]). For all three vaccines, breastfed infants had significantly lower IgG levels at six and 12 months of age. Except for higher Hib IgG levels at 12 months in infants fed low iron formula, the interventions did not affect vaccine IgG response. Unexpectedly, breastfed infants had significantly lower vaccine IgG levels compared to formula-fed infants.

Efficacy and safety of telitacicept in patients with lupus nephritis.

Although telitacicept is a promising drug for treating systemic lupus erythematosus, there are limited studies on its efficacy and safety in patients with lupus nephritis in China. This lack of research data restricts its potential for broader application and acceptance on a global scale. The present study aimed to determine the efficacy and safety of telitacicept in patients with lupus nephritis (LN) in China. Using a self-controlled before-after comparison method, patients with LN were recruited at Lishui Central Hospital between February 2022 and April 2023, who received telitacicept weekly as part of the standard treatment. Data on the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K), glucocorticoid dosing and the quantity of immunosuppressive medicines prescribed was collected. Additionally, serum complements, erythrocyte sedimentation rate (ESR), urinary protein levels, immunoglobulin concentrations, serum creatinine levels, plasma albumin concentrations, platelet counts and renal function parameters were documented throughout the study. A total of 13 patients were enrolled in the trial, comprising 11 women and two men. Following 12-48 weeks of treatment with telitacicept (80 or 160 mg per week), 84.6% (n=11) of all patients experienced symptom relief and their SLEDAI-2K score was reduced by more than four points. By the observation endpoint, the median glucocorticoid dosage of the 13 patients was decreased from 15 to 2.5 mg/d, and six patients discontinued their glucocorticoids. Furthermore, 46.1% of patients (n=6) reduced their dose and number of immunosuppressive medicines, while 15.4% (n=2) stopped their immunosuppressive medicines. Minimal changes were observed in serum creatinine, platelet count, C3 levels and C4 levels among patients. Immunoglobulin levels (IgG, IgA and IgM) remained stable or showed an upward trend. Plasma albumin levels remained within the normal range in three patients and increased in ten patients. It increased to the normal range in three of these ten patients. At the endpoint, ESR levels decreased in all patients. Additionally, three patients displayed varying degrees of renal function improvement, and their estimated glomerular filtration rate (ml/min/l.73 m2) increased from 127.8 to 134.2, 95.1 to 123.1 and 61.5 to 67.3, respectively. Urinary protein levels decreased in all patients. It decreased >0.5 g/l in seven patients and reached the normal levels in three patients. The adverse events of telitacicept were manageable. Among the patients infected with COVID-19, three patients had fever, 10 patients remained asymptomatic and none of them exhibited severe respiratory syndromes. In this study, telitacicept effectively stabilized LN activity and alleviated the clinical symptoms of most patients. Furthermore, it reduced the dose of glucocorticoid and immunosuppressive medicines. Therefore, telitacicept may be a promising treatment option for individuals with lupus nephritis.

Feeding Docosahexaenoic Acid and Arachidonic Acid during Suckling and Weaning Contributes to Oral Tolerance Development by Beneficially Modulating the Intestinal Cytokine and Immunoglobulin Levels in an Allergy-Prone Brown Norway Rat Model

BackgroundSuckling and weaning arachidonic acid (ARA) + docosahexaenoic acid (DHA) supplementation promoted oral tolerance (OT) development in pups, however, the effect of it on the intestine to promote OT development remains unknown. ObjectiveWe aimed to explore the impact of this supplementation on intestinal fatty acid composition, structure, and indicators that are supportive of OT development. MethodsAllergy-prone Brown Norway dams were randomly assigned to a control (0% ARA, 0% DHA) or ARA + DHA diet (0.45% ARA, 0.8% DHA) during suckling (0–3 wk). At weaning (3–8 wk), offspring were randomly assigned to a control (0% ARA, 0% DHA) or ARA + DHA diet (0.5% ARA, 0.5% DHA). At 3 wk, offspring in each group received an oral gavage of sucrose or ovalbumin (OVA) solution for five consecutive days. At 7 wk, all offspring received an intraperitoneal OVA injection. At 8 wk, offspring were terminated to evaluate jejunum morphology and measure mucosal food allergy-related secretory immunoglobulin A (sIgA) and cytokines, ileum phospholipid and triglyceride fatty acid compositions, and fecal calprotectin. ResultsWeaning ARA + DHA resulted in a higher percentage of DHA in ileum phospholipids and triglycerides (both P < 0.001), without affecting the percentage of ARA. Despite no lasting effect of suckling ARA + DHA on the DHA content in ileum phospholipids, a programming effect was found on the allergy-related intestinal immune profile [higher concentrations of mucosal IL-2 (P = 0.049) and sIgA (P = 0.033)]. OVA treatment resulted in a lower concentration of mucosal IL-6 (P = 0.026) regardless of dietary interventions. Offspring fed ARA + DHA during suckling and/or weaning had a higher concentration of mucosal transforming growth factor-beta (TGF-β) after OVA treatment but this was not observed in offspring fed control diets during suckling and weaning (P = 0.04). ConclusionsEarly life dietary ARA + DHA supplementation to allergy-prone rats enhanced the DHA concentration in intestinal phospholipids (weaning period) and increased the mucosal sIgA, IL-2, and TGF-β levels (suckling and weaning period), indicating its ability to create a tolerogenic intestinal environment to support OT development.

Physiological and hormonal changes between postmenopausal rheumatoid arthritis and systemic lupus erythematosus in women

It is thought that sex hormones are playing an actual role in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The purpose of this study was to determine the differences of some hematological, hormonal and immunological parameters between the postmenopausal women with rheumatoid arthritis and systemic lupus erythematosus. This study contained 75 postmenopausal women (52-65 years old). They included 25 women diagnosed with rheumatoid arthritis, 25 diagnosed with systemic lupus erythematosus and 25 normal controls. Blood was collected and used to determine complete blood count (CBC) and erythrocyte sedimentation rate (ESR) tests. Serum was separated and used to determine Follicle-stimulating hormone (FSH), Luteinizing Hormone (LH), Prolactin, cortisol, Estrogen, progesterone, testosterone, rheumatoid factor (RF) and Immunoglobulin E (IgE). The results indicated that both patients’ groups had anemia. However, the RA group had leukocytosis, but the SLE group had leukopenia. Moreover, thrombopenia occurred only in SLE patients. Although the levels of FSH and cortisol were significantly higher, the levels of LH, Estrogen and testosterone had significantly dropped in both patient groups. Interestingly, the level of progesterone was higher in the SLE and lower in the RA group. Moreover, the levels of RF, ESR and IgE were significantly increased in both patients’ groups. In conclusion, there were many differences in hematological and hormonal levels between postmenopausal women with rheumatoid arthritis and systemic lupus erythematosus. Such findings need future work to find out the reasons for these differences and how they could be used in future treatment strategies.

Evaluation of Level of Serum Immunoglobulin G, Serum Immunoglobulin M and Interleukin 10 in Hypertensive Patients

Abstract Background Hypertension is the leading risk factor for cardiovascular disease worldwide, accounting for 9.4 million deaths and 7% of global disability adjusted life years. The etiology of essential hypertension is unclear, and its mechanisms are complex Perturbations of the sympathetic and parasympathetic nervous systems, the reninangiotensin-aldosterone system, the endothelin system, genetic predisposition and environmental factors in combination or independently contribute to elevation of blood pressure (BP), and BP and/or the prohypertensive stimuli induce cardiovascular injury. Aim of the Work To measure levels of serum IgG, IgM, and IL10 in hypertensive patients as compared to healthy control. Patients and Methods This was a case-control clinical study that was conducted at the internal medicine outpatient clinic and wards of Ain Shams University hospitals on 100 subjects who weredivided into 2 groups. Results Interestingly our study showed that interleukin10 level was significantly lower in both treated and untreated hypertensives relative to control, this indicates that there is immune dysfunction in patients with essential hypertension. Additionally We found that there is significant correlation between CRP, neutrophils and hypertension among study group this confirm that inflammation plays a role in the pathogenesis of vascular disease. As expected we found the grade of progression of retinopathy andcarotid intima media thicknessincrease significantly with the degree of hypertension. Conclusion Hypertension may represent an extreme phenotype of a multifaceted and complex disease, it seems reasonable that more than one or perhaps a significant number of factors, including inflammatory and noninflammatory ones, may play a role in the pathogenesis of this syndrome. Although based on a relatively small number of patients, our results are provocative and support the importance of additional studies aimed at identifying laboratory markers that may relate to treatment resistance and ultimately to the development of new therapeutic strategies.

Evaluation of the effect of adding probiotic supplementation in patients with chronic spontaneous urticaria

Abstract Background: Altered microbiota has been implicated in the pathogenesis of chronic spontaneous urticaria (CSU). However, studies showing the effects of probiotic supplementation in CSU are scarce. Objectives: The objective of the study was to evaluate the efficacy of oral probiotic supplementation (Lactobacillus reuteri) in patients with CSU. Methods: This was a prospective, nonrandomized, parallel group, and controlled study. Oral probiotic supplementation (L. reuteri ATCC 55730 1 × 108 CFU) and a single dose of ebastine were introduced to 30 CSU patients, whereas a control group of 30 CSU patients received only a single dose of ebastine. Treatment responses, symptom control, and quality of life (QoL) were evaluated with Urticaria Activity Score 7 (UAS7), Physicians’ Global Assessment Visual Analog Score (PhyGA-VAS), and Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at weeks 0, 2, and 4. Results: There were significant decreases in the UAS7 and CU-Q2oL and increases in PhyGA-VAS both in the probiotic group and control group at weeks 2 and 4 (P &lt; 0.05; for all). The changes in the UAS7, CU-Q2oL, and PhyGA-VAS were significantly higher in the probiotic group than in the control group (P = 0.026; P = 0.001; and P = 0.004). The number of responders was significantly higher in the probiotic group than in the control group (83.3% vs. 50%, P = 0.006). Complete response and significant clinical improvement were observed in 9 (30%) and 20 (66.7%) patients in the probiotic group and 6 (20%) and 12 (40%) patients in the control group, respectively. High levels of total immunoglobulin E (≥100 IU/mL) were more frequent in probiotic nonresponders than in probiotic responders. Conclusion: Probiotics, when added to the standard therapy may improve the symptoms as well as the QoL scores in the treatment of CSU.

Assessment of the Presence of Predominantly Antibody Deficiency among Pediatric Patients with Interstitial Lung Disease

Abstract Background Predominantly antibody deficiencies (PADs) are frequent primary immunodeficiency diseases (PIDs) that have different etiologies. PAD patients present with various clinical manifestations, including infections and non-infectious disorders such as interstitial lung disease (ILD). The determination of serum Igs (IgG, IgM, IgA) is the first step in the evaluation of humoral immunity, and will help diagnose or at least point to a suspicion of quantitative Ig deficiencies. Lung disease is a frequent clinical manifestation in people living with primary immunodeficiency diseases, the most prevalent of which are common variable immunodeficiency disorders (CVID). Aim of Work Screening for Predominantly Antibody Deficiency (PAD) among pediatric patients diagnosed with primary interstitial lung disease. Patients and Methods This was a pilot study that was conducted on 30 children diagnosed with primary interstitial lung disease (ILD) following up in the Pediatric chest clinic, Children’s hospital, Ain Shams University in the period from September 2022 to February 2023, their ages ranged between 9-180 months and They were 16 (53.3%) males and 14 (46.7%) females. Tools of assessment included detailed clinical history with stress on history of respiratory symptoms, history of ten warning signs of immunedeficiency, general and chest examination and immunoglobulins (IgA, IgM, IgG) level by ELISA. Results There were 2 (6.7%) children with low levels of IgG, As regard IgM 2(6.7%) children had low levels, and 1(3.3%) child had high level. While 5 (16.7%) children had low levels of IgA. based on the criteria of Europian Society For Immunodeficiencies (ESID) 2 children were probable to be Commom Variable Immundeficiency (CVID) and 3 children were possible to be CVID. Conclusion Predominantly antibody deficiencies (PADs) may be presented as ILD and ILD may be the first presentation even before PID diagnosis.

Assessing the Quality of Care of Pregnant Patients With Thyrotoxicosis at an Urban Safety Net Hospital

ObjectiveThyrotoxicosis can adversely affect pregnancy. The quality of care (QoC) for thyrotoxicosis in pregnancy at a tertiary care safety net hospital was evaluated based on current guidelines. MethodsPregnant patients with thyrotoxicosis or a history of Graves disease who delivered in 2015-2021 were divided into 3 groups: low thyroid stimulating hormone (TSH), active Graves disease, and past Graves disease. The QoC was assessed using thyroid hormone and thyroid stimulating immunoglobulin (TSI) levels, fetal ultrasound, and endocrine referrals. We assessed potential impacts of race/ethnicity and socioeconomic status (SES). ResultsWe included 147 subjects (mean age 31.5 years, 76% Black, 86% non-Hispanic). Of patients with low TSH (n = 95), 75% had repeat TSH measurements and 33% had TSI measured. Hispanic patients were more likely to have TSI and repeat TSH measured than non-Hispanics (58% vs 29%; P = .04, and 100% vs 71%; P = .03, respectively). In patients with active Graves disease (n = 23, 70% treated with thionamides), 35% had free thyroxine levels at goal and 90% had endocrine care or referral. In patients with past Graves disease (n = 27), 56% had TSI measured, 78% had first-trimester TSH measurements, and 58% had TSH at goal. Black patients were less likely to have TSH checked in the first trimester than other races (85% vs 100%, P = .048). ConclusionThe QoC of thyrotoxicosis in pregnancy at this tertiary care center can be improved. A larger study is needed to assess the potential impacts of race and SES on the care of pregnant patients with thyrotoxicosis.

Comparison of the Effects of Hesperidin Over 30- and 60-Day Intervals on Rainbow Trout: A Potential Biostimulant to Promote Growth, Immunological and Antioxidant Responses, and Disease Resistance

Abstract The current research evaluated the effects of dietary hesperidin (HSP) on growth parameters, digestive enzyme activities, innate immune markers, and antioxidant responses in rainbow trout, Oncorhynchus mykiss after the 30- and 60-day feeding trial. Then, specimens were subjected to Yersinia ruckeri infection for 14 days. For this, six hundred rainbow trout juveniles (initial weight; 25.49±0.40 g) were fed with different levels of HSP including 0 (HSP0; control), 50 (HSP50), 100 (HSP100), 150 (HSP150), and 200 (HSP200) mg/kg feed. After 60 days, dietary HSP100 supplementation significantly improved growth and feed efficiency indices. The optimal dose of HSP based on the regression test for WG and FCR detected 122 and 131 mg/kg, respectively. At the end of the 30th day, dietary HSP150 supplementation markedly boosted serum lysozyme (LYZ), myeloperoxidase (MPO), complement component C3, and immunoglobulin (Ig) levels, but decreased malondialdehyde (MDA) content. In the same period, dietary administration of HSP at the different concentrations markedly increased complement component C4 (HSP150 and HSP200), superoxide dismutase (SOD), skin mucus alkaline phosphatase (ALP) (HSP100–HSP200), skin mucus LYZ and catalase (CAT) (HSP100 and HSP 150), and skin mucus Ig level (HSP50–HSP200). After 60 days, all dietary HSP supplementation significantly improved lipase, serum C3, glutathione peroxidase (GPX), and skin mucus ALP, LYZ, and Ig levels, but decreased MDA, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) values. After 60 days, dietary administration of HSP150 induced a significant discrepancy in the activity of serum LYZ, MPO, respiratory burst (RB), and lactate dehydrogenase (LDH) compared to the control group. In the same period, dietary HSP supplementation at different levels induced a remarkable increase in digestive protease activity (HSP100), serum ACH50 and CAT activities (HSP100 and HSP150), skin mucus peroxidase and serum SOD levels (HSP100–HSP200), and serum C4 value (HSP50, HSP150, and HSP200), but markedly decreased ALP activity (HSP150 and HSP200). In addition, dietary HSP supplementation, especially HSP150, markedly boosted disease resistance against Y. ruckeri infection. The current data demonstrated that the oral administration of 100–150 mg/kg HSP has a high potential to promote growth performance, disease resistance, and faster induction of immune and antioxidant responses.

Interleukin-17 Genotypes in Egyptian Asthmatic Children at Zagazig University Hospitals.

Bronchial asthma (BA) is increasing among Egyptian children. It is affected by multiple factors including genetic ones. In the current study, we assessedthe relationship between interleukin-17 (IL-17) genotypes and the occurrence of BA among Egyptian children. This case-control study included 100 participants. Group I (the control group) comprised 50 healthy subjects. Group II (the asthmatic group) comprised 50 subjects diagnosed with atopic asthma according tothe Global Initiative for Asthma. Measurement of serum Ig E and eosinophilic count was performed. Detection of single nucleotide polymorphism rs2275913 of IL-17 gene by restriction fragment length polymorphism-polymerase chain reaction was conducted. GA and AA genotypes were more frequent in the asthmatic group compared tothe control group (P = 0.03 and 0.01, respectively). Subjects carrying GA and AA genotypes were more susceptibleto have asthma [odds ratio (OR) = 2.21, 95% confidence interval (CI) = 1.14-9.94, P = 0.03; OR = 7.78, 95% CI = 1.59-38.3, P = 0.01, respectively]. The A allele was higher in the asthmatic group (33%) compared tothe control group (10%). A allele carriers were more susceptibleto have asthma (OR = 4.43, 95% CI = 2.04-9.82 and P < 0.001). Immunoglobulin E (IgE) levels and eosinophil percentages were higher among the carriers of GA and AA genotypes when compared with the GG genotype. All pulmonary function tests were significantly lower among carriers of AA genotype compared with GG genotype. An A allele carrier, AA genotype, increased IgE level, and eosinophil level were significant predictors for occurrence of asthma (P = 0.01, 0.02, 0.004, and 0.01). In conclusion, AA genotype carriers and A allele carriers of the IL-17 gene are more likely to have asthma compared with controls.

The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trial

The RTS,S/AS01E malaria vaccine showed lower antibody response and protective efficacy in infants aged 6-12 weeks compared with children aged 5-17 months (for whom this vaccine is recommended). We aimed to study the effect of previous Plasmodium falciparum exposure on the antibody responses to RTS,S/AS01E vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies. In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/AS01E phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous P falciparum exposure, which were later applied to RTS,S/AS01E-vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 P falciparum antigens using partial proteome microarrays. We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01E-vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior P falciparum exposure does not significantly affect antibody immunogenicity in children (Pearson's r=-0·02 [95% CI -0·13 to 0·10]). By contrast, high P falciparum exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6-12 months of life, correlated with reduced RTS,S/AS01E responses (r=-0·17 [-0·27 to -0·06]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage P falciparum antigens (r=-0·42 [-0·50 to -0·33]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=-0·44 [-0·55 to -0·33]), and involved antibodies to the central NANP region (r=-0·39 [-0·49 to -0·28]) but not the C-terminal region (r=0·02 [-0·10 to 0·15]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables. Interference between passive immunity and vaccine response is clinically significant and might affect the implementation of next-generation CSP-based vaccines for young infants and mothers as well as passive immunisation with human monoclonal antibodies. US National Institutes of Health, National Institute of Allergy and Infectious Diseases; PATH-Malaria Vaccine Initiative; Spanish Ministerio de Economía y Competitividad (Instituto de Salud Carlos III), European Regional Development Fund and European Social Fund; Fundación Ramón Areces; Spanish Ministry of Science and Innovation; and Generalitat de Catalunya (CERCA Program).

ISSUES OF ROUTING PATIENTS WITH AUTOIMMUNE HEPATITIS

Autoimmune hepatitis is a chronic, immune-mediated liver disease characterized by an increased level of immunoglobulins G and/or gamma globulins, the presence of autoantibodies and a typical histological picture. Diagnosis of autoimmune hepatitis causes difficulties due to various variants of the course, wide variability of the clinical picture, which leads to a large number of missed cases of the disease. Treatment of аutoimmune hepatitis is aimed at reducing the activity of an inadequate response of the immune system against cells of its own body and achieving complete remission of the disease. The timeliness of starting treatment is directly related to the prognosis of the disease. These features of the disease necessitate proper patient routing and shortening their path to specialists with knowledge and experience in managing this category of patients.

Respiratory and functional benefits of manual diaphragmatic release for cleaning-laborers exposed to occupational hazards.

To examine the respiratory and functional benefits of manual diaphragmatic release for Cleaning-Laborers Exposed to Occupational Hazards. A randomized controlled trial of 36 participants aged 35-45years was randomly allocated into two groups. The experimental group (n=18); received manual diaphragm release along with respiratory training exercises, and the control group (n=18); received respiratory training exercises only. Three times/week for 12 consecutive weeks. The serum immunoglobulin E level, pulmonary functions [forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and peak expiratory flow (PEF) rate (PEF)], chest wall mobility, and 6min walk-test performance were assessed pre- and post-intervention. There was a greater decline in serum immunoglobulin levels (p=0.003; Partial η2=0.23) and enhancement in pulmonary functions [FEV1 (p=0.025, Partial η2=0.14), FVC (p=0.017, Partial η2=0.16), FEV1/FVC (p=0.028, Partial η2=0.13), and PEF (p=0.012, Partial η2=0.17) in the experimental group. Further, there was a greater increase in chest mobility at the xiphoid level (p=0.002, Partial η2=0.25) in the experimental group, but this was not the case at the axillary level (p=0.29, Partial η2=0.03). Still, the 6min walk-test performance improved more significantly in the experimental group (p=0.002, Partial η2=0.24). The diaphragmatic release technique may offer a promising approach for mitigating distressing respiratory symptoms, enhancing immune function, and improving 6min walk-test performance among cleaning laborers with work-related respiratory hazards. The study was retrospectively registered at XXX (ID: NCT05802355).

BPIFA1 alleviates allergic rhinitis by regulating the NF-κB signaling pathway and Treg/Th17 balance.

Allergic rhinitis (AR) is an allergic condition characterized by inflammation of the nasal mucosa. Bacterial permeability-increasing family member A1 (BPIFA1) exhibits anti-inflammatory properties; however, its impact on AR remains unclear. Aim of this study is to investigate the expression and function of BPIFA1 in AR and its influence on inflammation and immune regulation in a mouse model of AR induced by ovalbumin (OVA). The expression of BPIFA1 was analyzed using quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Morphological assessments of nasal mucosal tissues were conducted. Levels of inflammatory mediators in nasal lavage fluid (NALF) and serum were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Protein expressions of BPIFA1, phosphorylated and total p65 (p-p65/p65), and IκBα were evaluated through Western blot analysis. The total cell counts, including epithelial cells, eosinophils, and lymphocytes in NALF, were determined using a hemocytometer. A mouse model of AR was established by OVA management. BPIFA1 expression was found to be reduced in the nasal mucosa tissues of patients with AR, suggesting a potential role in the disease's progression. We successfully developed a mouse model of AR, where BPIFA1 was similarly downregulated, indicating its possible involvement in modulating the NF-κB signaling pathway. Overexpression of BPIFA1 in this model attenuated inflammation and allergic responses by inhibiting the NF-κB pathway. Additionally, overexpression of BPIFA1 promoted the differentiation of regulatory T cells (Treg) and inhibited the differentiation of T helper 17 cells (Th17) in the NALF of AR mice, further demonstrating its regulatory impact on immune responses. The study confirmed that BPIFA1 upregulation reduced the levels of inflammatory cytokines TNF-α and IL-6, decreased infiltration of inflammatory cells, and modulated antigen-specific immunoglobulin levels and histamine in serum. BPIFA1 mitigated both inflammatory and allergic responses in AR mice induced by OVA through the modulation of the NF-κB signaling pathway and the balance between regulatory T cells (Treg) and T helper 17 cells (Th17). These findings suggest that BPIFA1 could serve as a novel biomarker and therapeutic target for AR, offering potential for the development of targeted treatments to improve patient outcomes.