Immunoglobulin Levels Research Articles

Extended long-term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha-mannosidosis.

Enzyme replacement therapy (ERT) using velmanase alfa previously showed promising efficacy and safety outcomes for up to 4 years of therapy in patients with alpha-mannosidosis. This pooled analysis from two multicenter, open-label phase IIIb extension trials rhLAMAN-07 (N = 13; NCT01908712) and rhLAMAN-09 (N = 8; NCT01908725) evaluated the long-term effects of velmanase alfa. Sixteen patients who previously completed phase I-III rhLAMAN-02/-03/-04/-05/-08 trials and five ERT-naïve patients were enrolled. Patients received 1 mg/kg velmanase alfa once weekly. Endpoints included changes from treatment baseline (before initial dose of velmanase alfa in any trial) in serum oligosaccharides, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function (forced vital capacity [FVC], % predicted), serum immunoglobulin G (IgG) levels, and adverse events. The overall cohort comprised 21 patients, divided by age at treatment baseline into pediatric (n = 14) and adult subgroups (n = 7). Distance walked according to 6MWT increased or stabilized in pediatric patients, while in adults either stabilization or slight decline was observed. Similarly, pediatric patients performed better in the 3MSCT. Changes in FVC, % predicted, were comparable in both subgroups up to ~6 years of observation, diverging thereafter. Overall, sustained serum oligosaccharide clearance and serum IgG level increase was observed upon treatment initiation and persisted until last common observation. Velmanase alfa treatment was generally well tolerated, with the majority of reported adverse events being of mild-to-moderate intensity. With follow-up of up to 12 years, long-term efficacy and safety outcomes indicate continued benefits of velmanase alfa in patients with alpha-mannosidosis.

Hematopoietic PI3Kδ deficiency aggravates murine atherosclerosis through impairment of regulatory T cells.

Chronic activation of the adaptive immune system is a hallmark of atherosclerosis. As PI3Kδ is a key regulator of T and B-cell differentiation and function, we hypothesized that alleviation of adaptive immunity by PI3Kδ inactivation may represent an attractive strategy counteracting atherogenesis. As expected, lack of hematopoietic PI3Kδ in atherosclerosis-prone Ldlr-/- mice resulted in hindered T- and B-cell numbers, CD4+ effector T cells, Th1 response, and immunoglobulin levels. However, despite markedly impaired peripheral proinflammatory Th1 cells and atheromatous CD4+ T cells, the unexpected net effect of hematopoietic PI3Kδ deficiency was aggravated vascular inflammation and atherosclerosis. Further analyses revealed that PI3Kδ deficiency impaired numbers, immunosuppressive functions, and stability of regulatory CD4+ T cells (Tregs), whereas macrophage biology remained largely unaffected. Adoptive transfer of wild-type Tregs fully restrained the atherosclerotic plaque burden in Ldlr-/- mice lacking hematopoietic PI3Kδ, whereas PI3Kδ deficient Tregs failed to mitigate disease. Numbers of atheroprotective B-1 and proatherogenic B-2 cells as well serum immunoglobulin levels remained unaffected by adoptively transferred wild-type Tregs. In conclusion, we demonstrate that hematopoietic PI3Kδ ablation promotes atherosclerosis. Mechanistically, we identified PI3Kδ signaling as a powerful driver of atheroprotective Treg responses, which outweigh PI3Kδ driven proatherogenic effects of adaptive immune cells like Th1 cells.

Efficacy of Qingying decoction and Wuling powder in the treatment of renal hematuria: A traditional Chinese medicine approach

Purpose: To investigate the efficacy of combining Qingying decoction with Wuling powder in the treatment of renal hematuria. Method: Seventy-six patients diagnosed with renal hematuria in the Emergency General Hospital and Nanmofang Community Health Service Center in Chaoyang District of Beijing, China were randomized equally into study and control groups. Control group received standard Western treatment in addition to Shenyan Rehabilitation tablets while study group received a combination of Qingying decoction and a modified Wuling powder alongside standard treatment for eight weeks. Treatment effectiveness was evaluated using urinary red blood cell count (URBC), urinary albumin-to-creatinine ratio (UACR), urinary β 2-microglobulin (β2-MG) and α 1-microglobulin (α1-MG) levels, serum levels of complement components 3 (C3) and 4 (C4), immunoglobulin A (IgA), and Traditional Chinese Medicine (TCM) syndrome scores. Results: There was a significant difference in total therapeutic effectiveness between study and control groups (p < 0.01). Study group showed significantly improved hematuria and total syndrome scores (p < 0.01). The study group showed significantly lower URBC, UACR, β 2-MG, α 1-MG, IgA, and C3 levels compared to the control group (p < 0.05). Conclusion: Treatment with Qingying decoction and Wuling powder demonstrates efficacy in managing renal hematuria, regulates urinary red blood cell counts, reduces symptoms, and lowers early renal impairment. Future studies in multiple centers using larger number of patients to determine the mechanisms of these drug actions and interactions and other related factors would be required.

Supplementation with whey peptide rich in β-lactolin improves trait anxiety and subjective stress in healthy adults: a randomized, double-blind, placebo-controlled study.

Mental disorders have become one of the most burdensome health concerns. We have previously demonstrated that whey-derived β-lactolin (glycine-thereonine-tryptophan-tyrosine tetrapeptide) activates dopaminergic systems and improves psychiatric function in rodents. However, the effects of β-lactolin on human mood states have not been investigated. This randomized, double-blind, placebo-controlled study aimed to evaluate the effects of supplementation with β-lactolin-rich whey peptide on human mood states. Sixty healthy adults (aged 45-64 years) with relatively low psychological health were randomly allocated to receive either whey peptide (containing β-lactolin 1.6mg/day) or placebo for 6 weeks. Mood states (primary outcomes) were evaluated using self-reporting questionnaires. Health-related quality of life (QOL), salivary stress marker and lipid mediator levels were evaluated as secondary outcomes. Compared with placebo, supplementation with β-lactolin improved changes in trait anxiety (p = 0.046), as assessed using the state-trait anxiety inventory, and in subjective stress (p = 0.043), as assessed using the Perceived Stress Scale. In the assessment of QOL, changes in the vitality subscale and mental health summary score of the 36-Item Short-Form Health Survey were improved in the β-lactolin group. The levels of salivary immunoglobulin A were significantly higher in the β-lactolin group. In a subgroup analysis by median age (54.5 years), subjective stress and salivary prostaglandin levels were significantly decreased by β-lactolin supplementation in the 45-54 -year-old subgroup. In conclusion, supplementation with β-lactolin improves trait anxiety, subjective stress, and psychological QOL, which may be associated with immunologic responses detected via salivary analysis.

Localized Pneumocystis jirovecii pneumonia in a malnourished, non-HIV-infected man in the absence of any established or diagnosed immunosuppressive condition: a case report

BackgroundPneumocystis jirovecii infection is an opportunistic infection that mostly affects patients with immunosuppressive conditions like human immunodeficiency virus (HIV) infection or medications, like corticosteroids. This study reports a rare case of Pneumocystis Jiroveci infection in a relatively immunocompetent patient which presented with uncommon radiological findings.Case presentationA 46-year-old man with a malnourished appearance and a history of opium dependence presented with dry cough, dyspnea, and weight loss to the hospital. There was no evidence of an immunocompromised condition or use of any immunosuppressive medication in the history of the patient. A lung high-resolution computed tomography (HRCT) scan revealed a crazy-paving appearance and localized infiltration. Methenamine silver staining and the histopathological findings in the transbronchial lung biopsy confirmed the diagnosis of PJP. Antibiotics and bronchodilators were administrated and the patient was discharged after 6 days of hospitalization. HIV testing and immunoglobulin levels were normal in the hospital course as well as his follow-up visits. After a 2-month follow-up, the patient was in good condition despite of mild remaining infiltration in his lung.ConclusionsPJP typically affects HIV-infected patients, but due to excessive use of immunosuppressive medications, its prevalence is increasing in non-HIV-infected patients. Malnutrition may predispose the patients to PJP, even in the absence of immunosuppressive conditions.

Shrimp allergy leading to severe transfusion reaction: A case report

AbstractBackgroundTransfusion reactions occur at an estimated incidence of 2 per 1.000 transfused products. Anaphylactic transfusion reactions are rarer, and seen in 1 per 10.000 transfusions, and are mostly related to platelet transfusions. Here, we describe a rare cause of a transfusion reaction.Case presentationA 19‐year‐old man underwent an allogeneic haematopoietic stem cell transplantation for sickle cell disease and developed an anaphylactic shock following a platelet transfusion, after excluding all common causes. The patient reported a shrimp allergy, and one of the blood/platelet donors had consumed shrimp the day before donation. Elevated levels of specific immunoglobulin E (IgE) against shrimp and tropomyosin were found in the patient. Subsequent transfusions were performed with apheresis platelets from selected donors who were instructed to avoid shrimp consumption, and these transfusions were uneventfully.ConclusionWhen a severe transfusion reaction occurs in a patient with a known food allergy, an IgE‐mediated (food‐related) transfusion reaction should be considered after excluding other causes.

7229 A Rare Case of Igg4 Hypophysitis Presenting as Hypogonadotropic Hypogonadism

Abstract Disclosure: C. Dimech: None. G. Jaiswal: None. Hypophysitis is a rare pituitary disorder including a broad range of inflammatory processes which affect the pituitary gland and infundibulum. Previously reported as 1 per 9 million individuals, the true incidence of hypophysitis per year is largely unknown due to the increase of novel etiologies such as immunoglobulin G4 (IgG4)- related disease. IgG4-related hypophysitis (IgG4-RH) was first clinically described in 2004 and later biopsy proven in 2007. The main clinical features are elevated serum IgG4 level and IgG4-positive lymphocyte infiltration of tissues on histopathology. IgG4-RH is reported to account for 1.3% of primary hypophysitis with 3.2:1 incidence ratio of men to women, in the 6th decade of life. Here we present a case of a 68-year-old Caucasian male who presented for evaluation of hypogonadotropic hypogonadism. As fasting morning testosterone levels were significantly low, MRI pituitary was completed which revealed a homogenously enhancing pituitary gland with thickened, nodular enhancement of the pituitary infundibulum. Subsequent lab work-up revealed normal function of remaining anterior pituitary without evidence of central vasopressin deficiency. Evaluation of underlying etiologies was unremarkable except for significantly elevated IgG4 levels (472mg/dL). Based on the significantly elevated IgG-4 levels (>135 mg/dl) and the radiographic findings of the pituitary infundibulum, the diagnosis of possible IgG4-RH was made. The patient was initiated on treatment with rituximab and glucocorticoid therapy with prednisone. Following 3 months of medical therapy, MRI pituitary showed resolution of stalk inflammation, confirming diagnosis of IgG4- RH. Presentation: 6/1/2024

Chromone components of Saposhnikovia divaricate attenuate rheumatoid arthritis development by inhibiting the inflammatory response

Ethnopharmacological relevanceSaposhnikovia divaricata (Turcz.) Schisck., a traditional Chinese medicine (TCM), has historically been utilized in the clinical treatment of RA. It was initially documented in the 'Shennong Ben Cao Jing' as a superior quality, with the text stating: 'The herb is widely renowned for its efficacy in alleviating whole-body discomfort, bone pain, malaise, and promoting long-lasting vitality. Chromones (CHR) were identified as the primary active components in Saposhnikovia divaricata. However, the specific molecular mechanisms by which CHR impacts RA remain incompletely understood. Aim of the studyTo explore the therapeutic efficacy of CHR, a class of compound derived from Saposhnikovia divaricata, in alleviating arthropathy and immune hyperactivity in a collagen-induced arthritis (CIA) mouse model. Material and methodsSurface plasmon resonance (SPR) molecular fishing and UHPLC-QTOF/MS technology were used to identify CHR in Saposhnikovia divaricata as an active ingredient for treating RA. A CIA mouse model was used to verify the anti-RA effect of CHR in vivo. The anti-RA efficacy of CHR in vivo was evaluated by body weight change, joint swelling, arthritis index, immune organ index, ankle joint disease, and immunoglobulin G (IgG) content. The mechanism of improving RA was further analyzed by a protein chip assay and verified by Western blotting. ResultsCHR treatment reduced swelling, arthritis index, and IgG, IgG1, IgG2a, and IgG2b levels in CIA mice. Protein microarray indicated that CHR mitigated CIA-induced joint inflammation by inhibiting immune cell activation, reducing the expression of inflammatory factors and chemokines, potentially by modulating the rheumatoid arthritis pathway involving tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and chemokines. This hypothesis was supported by the upregulation of bone morphogenetic proteins 3 (BMP3) and phospho-Smad2 (p-Smad2) proteins, coupled with the downregulation of interleukin-6 (IL-6), interleukin-1β (IL-1β), TNF-α, and IL-17A proteins in the joints of CHR-treated mice. ConclusionCHR shows promise as a potential therapeutic agent for RA, exerting its effects through anti-inflammatory mechanisms.

Pharmacokinetics, Pharmacodynamics, and Safety of Intravenous Efgartigimod and Subcutaneous Efgartigimod PH20 in Healthy Chinese Participants.

Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and Chinafor the treatment of gMG. We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants. In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 3:1 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters. After the fourth IV infusion, a mean maximum observed concentration (Cmax) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC0-168h) was 5300 µg × h/mL. After the fourth SC injection, a mean Cmax of 42.1 µg/mL was achieved with a median Tmax of 47.74 h; the mean AUC0-168h was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study. The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. Both formulations effectively reduced total IgG levels by a similar percentage. CTR20211952 and CTR20211805.

8105 Radiation-Induced Hyperthyroidism in the Context of Palliative Radiation Therapy

Abstract Disclosure: A. Randhawa: None. G. Palaguachi: None. J.G. Karam: None. Introduction: Palliative radiotherapy, designed to alleviate focal symptoms in advanced, incurable cancer, aims to enhance quality of life with minimal treatment burden. The thyroid gland's susceptibility to neck radiation is known, primarily leading to hypothyroidism. However, hyperthyroidism is a much less frequently reported adverse effect that is poorly understood. This case report highlights an unusual instance of radiation-induced hyperthyroidism. Case Presentation:The patient is a 53 years-old woman with history of Ewing’s sarcoma of the sacrum diagnosed in August 2022, treated initially with chemotherapy (cyclophosphamide, vincristine, etoposide and ifosfamide), but diagnosed with leptomeningeal metastasis and T12/L1 mass in October 2023 when she presented with lower extremities weakness and urinary incontinence. She underwent T12-L1 laminectomy, resection of tumor and fusion, and was started on palliative intent radiation therapy for the brain and C-spine. A month later, she was admitted for altered mental status and was found to be persistently tachycardic at 140 bpm. Thyroid function testing was sent and revealed hyperthyroidism with TSH of 0.07 mIU/L (0.39-4.08), Free T4 of 1.74 ng/dl (0.58-1.64), T4 of 10.7ug/ml (4.4-9.5), T3 of 0.54 ng/ml (0.72-1.35), with undetectable Thyroid Peroxidase Antibodies and Thyroid Stimulating Immunoglobulin level. Thyroid Ultrasound showed a small and homogenous thyroid gland with no discrete nodules. Radioactive Iodine uptake and scan was not obtained because of exposure to iodized contrast during hospital stay. The patient had no available baseline thyroid function tests. She had no recent fever or viral illness. Unfortunately, her clinical condition deteriorated rapidly, and she passed away on the seventh day of admission. Conclusion: While hypothyroidism is a well-established consequence of high-dose irradiation, the mechanisms behind the rarer radiation-induced hyperthyroidism remain unclear. Speculation includes the release of autoantigens from damaged thyroid glands, triggering an immune response and potentially leading to Graves' hyperthyroidism. However, our case more likely represents a hyperthyroid phase in the triphasic sequence of destructive subacute thyroiditis, given the absence of elevated thyroid antibodies, thyroid nodules, and other causes of thyroiditis. Increasing awareness of radiation-induced hyperthyroidism, unraveling its mechanisms, and refining diagnostic strategies such as obtaining baseline and monitoring thyroid function testing are crucial, particularly in the context of palliative therapy, where striking the delicate balance between efficacy and minimizing toxicity is paramount. Presentation: 6/3/2024

Effectiveness of double-filtration plasmapheresis in reducing immunoglobulin and culprit antibody levels in neuroimmune disorders: A single-center retrospective analysis from China

ObjectiveThis study aims to evaluate the effectiveness of double-filtration plasmapheresis (DFPP) in reducing immunoglobulins and culprit antibodies in neuroimmune disorders. MethodsA retrospective analysis was conducted on 51 patients with neuroimmune diseases treated with DFPP, immunotherapy, and symptomatic treatment. Immunoglobulin and antibody levels were measured pre- and post-treatment, along with neurological function assessments using scales like the modified Rankin Scale (mRS), Expanded Disability Status Scale (EDSS), Clinical Assessment Scale for Autoimmune Encephalitis (CASE), and Myasthenia Gravis-specific scales. ResultsThe cohort included patients with neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalitis (AIE), myasthenia gravis (MG), anti-myelin oligodendrocyte glycoprotein associated disease (MOGAD), and paraneoplastic neurological syndromes (PNS). DFPP significantly reduced immunoglobulin levels (IgG, IgA, IgM) by ∼70 %. Most patients showed decreased antibody titers and significant neurological improvement. The median mRS score improved from 2 (IQR 2–3) to 1 (IQR 1–2) post-treatment, with further improvement at 90 days. Notable improvements were observed across various scales specific to NMOSD, MOGAD, AIE, and MG. Minor adverse events were reported, with no serious adverse events. ConclusionsDFPP is effective in reducing immunoglobulin and antibody levels, leading to improved neurological function in neuroimmune disorders. Further large-scale studies are warranted to confirm these findings.

Study of the Immune And Inflammatory Biomarkers Associated With Dehydration In Children

Background: The current study investigated the relationship between dehydration and its causes, as well as the influence on inflammatory cytokines. Method: 125 samples were collected from children with dehydration due to diarrhea. 95 samples were collected from healthy children. All samples were obtained from the Maternity and Children's Hospital in Diwaniyah city from February to July 2023. Result: Children with dehydration from diarrhea and other causes showed increased levels of inflammatory cytokines and immunoglobulins (IgG, IgA, IgM). This indicates a relationship between dehydration and inflammatory cytokines. Conclusion: The study found a connection between dehydration and elevated inflammatory cytokines in children with diarrhea-induced dehydration.

The relationship between aflatoxin M1 and immunoglobulin levels in cows' colostrum.

The purpose of the present research was to assess the amounts of aflatoxin M1 (AFM1) and immunoglobulin (IgA, IgG, and IgM) in cow colostrum samples, as well as their relationship. The sampling involved 90 cows (54 Montofon and 36 Simmental) from 15 independent farms. An appropriate number of samples from the total mixed ration (TMR) used in feeding the cows were collected simultaneously with the colostrum samples. AFB1 in feed, AFM1, and immunoglobulin (IgA, IgG, and IgM) levels in colostrum were evaluated using the ELISA method. The AFM1 level in colostrum samples exceeded the maximum allowed values for raw milk. Ig levels were higher in Montofon-breed cows' colostrum than in Simmentals. However, it was determined that neither the breed nor the lactation number significantly affected the colostrum Ig level. It was determined that there was no linear relationship between the number of lactations and immunoglobulin levels or between AFM1 and immunoglobulin levels in colostrum. Similarly, it was determined that there was no linear relationship between the AFB1 level in the feed and the AFM1 level in the colostrum of animals consuming these feeds.

Relationship between infant gastrointestinal microorganisms and maternal microbiome within 6 months of delivery.

To investigate the association between the microbiota in mothers and gut microbiota in infants from 0 to 6 months, the microbiotas in infant feces, maternal feces, and breast milk were determined by 16S rRNA gene sequencing. The contribution of each maternal microbiome to the infant was assessed using fast expectation-maximization for microbial source tracking calculations. The levels of short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA) in the feces of infants were also determined using gas chromatography and IDK-sIgA ELISA to gain a more comprehensive understanding of the infant gut microbiome. The results of this study showed that in addition to Firmicutes (E1) and Bifidobacterium (E2), the dominant microorganisms of the intestinal microbiota of infants aged 0-6 months include Proteobacteria, which is different from previous findings. Acetic acid, the most abundant SCFA in the infant gut, was positively correlated with Megasphaera (P < 0.01), whereas sIgA was positively correlated with Bacteroides (P < 0.05) and negatively correlated with Klebsiella and Clostridium_XVIII (P < 0.05). The maternal gut microbiota contributed more to the infant gut microbiota (43.58% ± 11.13%) than the breast milk microbiota, and significant differences were observed in the contribution of the maternal microbiota to the infant gut microbiota based on the delivery mode and feeding practices. In summary, we emphasize the key role of maternal gut health in the establishment and succession of infant gut microbiota.IMPORTANCEThis study aims to delineate the microbial connections between mothers and infants, leveraging the fast expectation-maximization for microbial source tracking methodology to quantify the contribution of maternal microbiota to the constitution of the infant's gut microbiome. Concurrently, it examines the correlations between the infant gut microbiota and two distinctive biomolecules, namely short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA). The findings indicate that the maternal gut microbiota exerts a greater influence on the infant's gut microbial composition than does the microbiota present in breast milk. Infants born via vaginal delivery and receiving mixed feeding display gut microbiota profiles more similar to their mothers'. Notably, the SCFA acetate displays positive associations with beneficial bacteria and inverse relationships with potentially harmful ones within the infant's gut. Meanwhile, sIgA positively correlates with Bacteroides species and negatively with potentially pathogenic bacteria. By delving into the transmission dynamics of maternal-infant microbiota, exploring the impacts of metabolic byproducts within the infant's gut, and scrutinizing how contextual factors such as birthing method and feeding practices affect the correlation between maternal and infant microbiota, this research endeavors to establish practical strategies for optimizing early-life gut health management in infants. Such insights promise to inform targeted interventions that foster healthier microbial development during the critical first 6 months of life.

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.