Elevated Levels Of Immunoglobulin Research Articles

Waldenstrom's Macroglobulinemia: A Case Report

Waldenström's macroglobulinemia (WM) is a rare, slow-growing hematologic malignancy marked by elevated levels of monoclonal immunoglobulin M (IgM) and bone marrow infiltration by lymphoplasmacytic cells. This case details a 72-year-old man who, during a pre-anesthetic consultation for lumbar spinal stenosis surgery, presented with neurological symptoms, fatigue, and headaches. Examination revealed pallor, and laboratory tests indicated anemia and an elevated erythrocyte sedimentation rate. Serum protein electrophoresis identified a monoclonal IgM spike, and bone marrow aspiration showed significant infiltration by small lymphoid cells, lymphoplasmacytoid cells, and plasma cells. WM was confirmed, and the patient was treated with dexamethasone, rituximab, and cyclophosphamide, with positive follow-up progress. This case underscores the importance of considering WM in the differential diagnosis for patients with unexplained anemia and elevated IgM levels, highlighting the need for timely diagnosis and treatment to manage potential complications.

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.

Effect of period supplementation of Saccharomyces boulardii in humoral immune response of sheep immunized with recombinant chimera of Paeniclostridium sordellii

Saccharomyces boulardii has emerged as a promising probiotic agent in bolstering the immune system. In vaccinology, its application can be explored to optimize vaccine efficacy by augmenting host immune response and consequently enhancing the immunogenicity of antigenic formulations. However, it is imperative to conduct further research to comprehend the effectiveness of this probiotic in novel vaccines targeting significant pathogens affecting animal health. Hence, this study investigated the effects of a short (3 - 5 days) or continuously (56 days) S. boulardii supplementation (3 × 108 CFU/mL) on the adaptive immunity of sheep immunized with a recombinant antigen against Paeniclostridium sordellii (rAPS). Four immunized groups (G1-G4) were evaluated, varying the regimen of S. boulardii supplementation. Elevated levels of anti-rAPS IgG immunoglobulins were detected in all vaccinated animals. Daily supplementation with S. boulardii (G1) resulted in higher IgG levels, reaching antibody titers of up to 25,600, which were 16 times higher than those observed in not supplemented group (G4) and 4 times higher than in the group supplemented for 3 days (G3) or 5 days (G2) before each immunization. These findings demonstrate that S. boulardii can enhance vaccine-induced immune responses against P. sordellii, particularly IgG-mediated immune responses in sheep. The possibility of a short supplementation for 5–3 days is a very important finding for animal husbandry, considering the supplementation and supply management cost.

Pathogenicity of Aeromonas veronii from Nile Tilapia (Oreochromis niloticus) and Efficacy of Fish Oral Vaccine against Motile Aeromonad Septicemia in Tank Trials

Motile aeromonad septicemia (MAS), caused by the Aeromonas species, has been a serious problem in fish health management, particularly in Nile tilapia (Oreochromis niloticus). This study characterized an Aeromonas species isolated from farmed tilapia fingerlings in Binangonan, Rizal, Philippines, and tested for its pathogenicity in tank trials. The isolate, designated as Aeromonas veronii DFR01 (Diseased Fish Rizal), was identified based on 16S rRNA phylogenetic analysis, 16S rRNA homology, and MALDI-TOF mass spectrometry. Its biochemical profile was generated from API and Biolog Gen III systems. A median lethal dose of A. veronii DFR01 was determined to be 107 CFU/mL in tank trials and was utilized as a whole-cell inactivated antigen for oral vaccine development. The immunized tilapia fingerlings produced elevated levels of immunoglobulin M (IgM) in the blood as determined by an enzyme-linked immunosorbent assay (ELISA). There was a significant increase in IgM levels 14 days post-vaccination. A quantitative polymerase chain reaction (qPCR) showed increasing levels of IgM gene expression after vaccination until 38 days of culture. Vaccinated fish showed 25–35% cumulative mortality after the challenge, while non-vaccinated-challenged fish showed 75% mortality. The findings of this research suggest that the fish oral vaccine may prove beneficial for farmed tilapia populations. The vaccine elicited improved immune responses in the fish and resulted in higher survival rates.

Estimating Prevalence of Asthma Among Children Associated With Raised IgE Immunoglobulin: A Cross-Sectional Study

Objective: To estimate the prevalence of asthma among children associated with elevated IgE immunoglobulin levels. Methodology: A cross-sectional study was conducted at Memon Charitable Hospital, Hyderabad from January 2022 to December 2022. The study participants were children aged between 6-12 years. Children who have previously been diagnosed with asthma or have other chronic respiratory conditions were excluded from the study. IgE test was performed along with assessing the clinical symptoms of asthma. All data collected was stored securely and confidentially, with access limited to the research team only. Result: A total of n-781 patients aged 6 to 12 years were enrolled in the study. The mean age of the patient was reported to be 6.84 ± 2.94 in age group of 6-9 years where as 10.65 ± 3.20 in age group of 10-12 years. Boys were found to be more affected with asthma as compared to girls with frequency of 260 (61.75%) and 209 (58.05%) as compared to girls in both age group. The total prevalence of asthma was found to be 9.23%. Conclusion: That asthma is a significant health concern in this population, with observed prevalence associated with elevated IgE immunoglobulin levels to be 9.23%, and efforts to prevent, diagnose, and manage the disease should be prioritized.

Organ-specific Toxocara canis larvae migration and host immune response in experimentally infected mice.

We investigated organ specific Toxocara canis larval migration in mice infected with T. canis larvae. We observed the worm burden and systemic immune responses. Three groups of BALB/c mice (n=5 each) were orally administered 1,000 T. canis 2nd stage larvae to induce larva migrans. Mice were sacrificed at 1, 3, and 5 weeks post-infection. Liver, lung, brain, and eye tissues were collected. Tissue from 2 mice per group was digested for larval count, while the remaining 3 mice underwent histological analysis. Blood hematology and serology were evaluated and compared to that in a control uninfected group (n=5) to assess the immune response. Cytokine levels in bronchoalveolar lavage (BAL) fluid were also analyzed. We found that, 1 week post-infection, the mean parasite load in the liver (72±7.1), brain (31±4.2), lungs (20±5.7), and eyes (2±0) peaked and stayed constant until the 3 weeks. By 5-week post-infection, the worm burden in the liver and lungs significantly decreased to 10±4.2 and 9±5.7, respectively, while they remained relatively stable in the brain and eyes (18±4.2 and 1±0, respectively). Interestingly, ocular larvae resided in all retinal layers, without notable inflammation in outer retina. Mice infected with T. canis exhibited elevated levels of neutrophils, monocytes, eosinophils, and immunoglobulin E. At 5 weeks post-infection, interleukin (IL)-5 and IL-13 levels were elevated in BAL fluid. Whereas IL-4, IL-10, IL-17, and interferon-γ levels in BAL fluid were similar to that in controls. Our findings demonstrate that a small portion of T. canis larvae migrate to the eyes and brain within the first week of infection. Minimal tissue inflammation was observed, probably due to increase of anti-inflammatory cytokines. This study contributes to our understanding of the histological and immunological responses to T. canis infection in mice, which may have implications to further understand human toxocariasis.

THE INFLUENCE OF ATOPY ON CYSTIC FIBROSIS COURSE IN CHILDREN

The relevance of research. The course of cystic fibrosis (CF) depends on the influence of different modifying factors. One of these factors is atopy. The role of atopy in CF course is incompletely determined today and requires further study. The purpose of the study: to improve medical care for patients with CF by clarifying the pathogenetic role of atopy in the disease course. Materials and methods. Analysis of data from a clinical and paraclinical examination of 42 children with CF in the Kharkiv region. Patients were divided into two groups: with an elevated level of total immunoglobulin E (n=19) and with a normal level of this indicator (n=23) to determine the features of CF course depending on the atopy presence. Results and discussion. In the group with elevated and normal levels of total serum IgE, boys were predominant, as in the general population, and accounted for 73.6% and 60.8%, respectively. The first manifestations of CF were represented mainly by intestinal signs in both groups at 68.4% and 73.9% of cases, respectively. Data analysis of the clinical features of CF course in children with elevated level of IgE (severity of lung and liver lesions) revealed results without significant differences between groups. High level of sensitivity to ordinary domestic, food and pollen allergens was not detected in children of group with elevated level of IgE. Patients with CF and atopy were found to have a probable increase in the levels of CD3, IgM, spontaneous NBT; phagocytosis of latex; decreasing in the levels of CD4, IgA compared to the group with a normal level of total IgE. Conclusion. Features of the CF phenotype associated with the atopy were analyzed. The received data can be used when determining the treatment algorithm, taking into account the individual characteristics of the disease course.

MULTIPLE GIANT CHALAZIA IN HYPERIMMUNOGLOBULINEMIA E SYNDROME: A CASE REPORT

Introduction : Hyperimmunoglobulinemia E syndrome (HIES) is a rare primary immunodeficiency disorder that manifests as elevated level of serum immunoglobulin E (IgE) higher than 1.000 IU/mL and multisystem disorder characterized by recurrent skin and pulmonary abscesses caused by autosomal dominant or recessive disorder with gene mutation. We present a case of multiple giant chalazion ina patient with HIES.
 Case Illustration : A 15-year-old boy was referred to Ophthalmology Department with multiple giant lumps on the left eyelid for the last 2 weeks. He had a history of recurrent multiple lumps on the left lower eyelid in the last 1 year. He was diagnosed with HIES since 8 years ago. He had normal visual acuity of both eyes. Multiple giant chalazion were observed on the left upper and lower eyelid. The patient also presented with scalp and neck infection. Laboratory studies showed elevated total serum IgE level of 53,032 IU/mL and eosinophilia.
 Discussion : Ocular manifestations in HIES patients are not common. Some cases reported chalazia, keratoconus, and blepharitis. Surgical incision drainage was performed in our patient. Medications and surgical intervention had produced only transient improvement. The patient was treated conservatively. Riskof chalazia recurrence remains unknown as reported cases presented with diverse clinical presentation and follow-up serum IgE evaluation is not routinely performed.
 Conclusion : Recurrent multiple giant chalazia may occur as an ophthalmic feature of HIES. HIES should be considered and investigated in patients presenting with recurrent giant chalazia.

MULTIPLE GIANT CHALAZIA IN HYPERIMMUNOGLOBULINEMIA E SYNDROME: A CASE REPORT

Abstract
 Introduction : Hyperimmunoglobulinemia E syndrome (HIES) is a rare primary immunodeficiency disorder that manifests as elevated level of serum immunoglobulin E (IgE) higher than 1.000 IU/mL and multisystem disorder characterized by recurrent skin and pulmonary abscesses caused by autosomal dominant or recessive disorder with gene mutation. We present a case of multiple giant chalazion ina patient with HIES.
 Case Illustration : A 15-year-old boy was referred to Ophthalmology Department with multiple giant lumps on the left eyelid for the last 2 weeks. He had a history of recurrent multiple lumps on the left lower eyelid in the last 1 year. He was diagnosed with HIES since 8 years ago. He had normal visual acuity of both eyes. Multiple giant chalazion were observed on the left upper and lower eyelid. The patient also presented with scalp and neck infection. Laboratory studies showed elevated total serum IgE level of 53,032 IU/mL and eosinophilia.
 Discussion : Ocular manifestations in HIES patients are not common. Some cases reported chalazia, keratoconus, and blepharitis. Surgical incision drainage was performed in our patient. Medications and surgical intervention had produced only transient improvement. The patient was treated conservatively. Riskof chalazia recurrence remains unknown as reported cases presented with diverse clinical presentation and follow-up serum IgE evaluation is not routinely performed.
 Conclusion : Recurrent multiple giant chalazia may occur as an ophthalmic feature of HIES. HIES should be considered and investigated in patients presenting with recurrent giant chalazia.

The Cellular Dysfunction of the Brain-Blood Barrier from Endothelial Cells to Astrocytes: The Pathway towards Neurotransmitter Impairment in Schizophrenia.

Schizophrenia (SCZ) is an articulated psychiatric syndrome characterized by a combination of genetic, epigenetic, and environmental factors. Our intention is to present a pathogenetic model combining SCZ alterations and the main cellular actors of the blood-brain barrier (BBB): endothelial cells (ECs), pericytes, and astrocytes. The homeostasis of the BBB is preserved by the neurovascular unit which is constituted by ECs, astrocytes and microglia, neurons, and the extracellular matrix. The role of the BBB is strictly linked to its ability to preserve the biochemical integrity of brain parenchyma integrity. In SCZ, there is an increased BBB permeability, demonstrated by elevated levels of albumin and immunoglobulins in the cerebrospinal fluid, and this is the result of an intrinsic endothelial impairment. Increased BBB permeability would lead to enhanced concentrations of neurotoxic and neuroactive molecules in the brain. The pathogenetic involvement of astrocytes in SCZ reverberates its consequences on BBB, together with the impact on its permeability and selectivity represented by the EC and pericyte damage occurring in the psychotic picture. Understanding the strict interaction between ECs and astrocytes, and its consequent impact on cognition, is diriment not only for comprehension of neurotransmitter dyshomeostasis in SCZ, but also for focusing on other potential therapeutic targets.

Add-on immunosuppressive therapy may benefit selected patients with primary biliary cholangitis and autoimmune phenomena.

Mildly elevated levels of transaminase and/or immunoglobulin G (IgG) are common in patients with primary biliary cholangitis (PBC). It is still unclear whether adding immunosuppressive therapy to ursodeoxycholic acid (UDCA) benefits those patients who are not fulfilling the diagnostic criteria of PBC with autoimmune hepatitis (AIH) features. To assess the efficacy of adding immunosuppressive therapy to UDCA for patients with PBC and autoimmune phenomena but not fulfilling the diagnostic criteria of PBC with AIH features. This is a retrospective-prospective cohort study in a tertiary medical center. Patients with PBC and autoimmune phenomena were defined by the elevation of IgG and/or transaminase but did not fulfill the diagnostic criteria of PBC with AIH features. We grouped these patients based on with and without add-on immunosuppressive therapy and balanced their baseline characteristics using inverse probability treatment weighting (IPTW). A total of 652 patients with PBC and autoimmune phenomena were included, with a median follow-up of 4.08 years. After IPTW, the pseudo sample size in the add-on therapy and monotherapy groups was 558 and 655, respectively. After 1 year of observation, patients in the add-on therapy group had a higher biochemical response rate (normalization of transaminase and IgG levels) (49% versus 17%, p < 0.001). Furthermore, add-on therapy improved the transplant-free survival in the subgroup of patients with PBC and transaminase ⩾3 × upper limit of normal (ULN) or IgG ⩾1.3 × ULN (p = 0.033). Add-on immunosuppressive therapy may improve the normalization rates of transaminase and IgG levels in all patients with PBC and mildly elevated transaminase and IgG levels and the long-term outcomes in the subgroup of the patients with transaminase ⩾3 × ULN or IgG ⩾1.3 × ULN.

A Novel, Comprehensive A129 Mouse Model for Investigating Dengue Vaccines and Evaluating Pathogenesis.

In search of a mouse model for use in evaluating dengue vaccines, we assessed A129 mice that lacked IFN-α/β receptors, rendering them susceptible to dengue virus (DENV) infection. To our knowledge, no reports have evaluated dengue vaccine efficiency using A129 mice. A129 mice were given a single intraperitoneal (IP) or subcutaneous (SC) injection of the vaccine, Dengvaxia. After 14 days of immunization via the IP or SC injection of Dengvaxia, the A129 mice exhibited notably elevated levels of anti-DENV immunoglobulin G and neutralizing antibodies (NAb) targeting all four DENV serotypes, with DENV-4 displaying the highest NAb levels. After challenge with DENV-2, Dengvaxia and mock-immunized mice survived, while only the mock group exhibited signs of morbidity. Viral genome levels in the serum and tissues (excluding the brain) were considerably lower in the immunized mice compared to those in the mock group. The SC administration of Dengvaxia resulted in lower viremia levels than IP administration did. Therefore, given that A129 mice manifest dengue-related morbidity, including viremia in the serum and other tissues, these mice represent a valuable model for investigating novel dengue vaccines and antiviral drugs and for exploring dengue pathogenesis.

Risk Stratification Models Overestimate Progression Risk in Contemporary Patients with Smoldering Multiple Myeloma (SMM)

Introduction: SMM is an asymptomatic precursor of multiple myeloma (MM), affecting ~1 in 200 people aged &amp;gt;40 years. Historically, risk of progression from SMM to MM was 10% per year in the first 5 years. However, since then, the definition and characteristics of the SMM patient population have changed substantially. First, IMWG diagnostic criteria for MM in 2014 changed to include biomarker-only myeloma (SLiM), reclassifying asymptomatic patients previously considered SMM. Second, incorporation of advanced imaging (CT, PET/CT, MRI) identified bone disease with greater sensitivity. Hence, we hypothesized that in the contemporary era, the risk of progression from SMM to MM would be markedly lower than historically. Methods: We performed a retrospective cohort study of consecutive patients with SMM at Columbia University Irving Medical Center from 2014-2022 and observed without therapeutic intervention. Our primary objective was to measure cumulative incidence of progression to MM and to characterize progression events. We also calculated predicted 2-year risk of progression by different risk-stratification models (Mayo 20/2/20, PANGEA, IMWG SMM model) in our cohort. Results: 102 consecutive patients with SMM were included. Median year of diagnosis was 2019 (range, 2014-2022). Baseline clinical and demographic characteristics of the cohort are shown in Table 1. The three most common scenarios that led to SMM diagnosis were workup of anemia/cytopenias(s) (n=22; 21.8%), incidental protein gap or elevated immunoglobulin level (n=20; 19.8%), and renal dysfunction (n=16; 15.8%). The racial/ethnic makeup of our study cohort was 38% Hispanic/Latino, 38% Non-Hispanic White, 19% Black/African-American, and 5% Asian. Bone disease was ruled out by advanced imaging (whole body CT, PET/CT, WB-MRI, and/or MRI spine+ pelvis) in 81.2% of patients. The most common abnormality on FISH was hyperdiploidy (39.2%), followed by t(11;14) (22.1%), with ≥1 high-risk cytogenetic abnormality (HRCA) in 35% of patients. Median follow-up was 45 months (95% CI, 34-52). 22/102 patients (21.6%) progressed to symptomatic plasma cell dyscrasia: CRAB myeloma in 18, SLiM myeloma in 1, systemic AL amyloidosis in 3 patients. The cumulative incidence of progression to MM (CRAB/SLiM) at 1, 2, 3, and 4 years from SMM diagnosis was 3.1% (95% CI, 0.99-9.1), 7.7% (95% CI, 3.7-15.3), 13.9% (95% CI, 8.1-23.1), and 17.1% (95% CI, 10.3-27.1) respectively [Figure 1]. Notably, presence of HRCA by FISH had a dose-dependent increase in risk of progression, with the 2-year risk being 75% (95% CI, 24-97%) in patients with ≥2 HRCA vs 13.0% (95% CI, 5.9-26.3) in those with 0-1 HRCA respectively ( p=0.0049). Among 18 patients who progressed to CRAB myeloma, the myeloma-defining event/s (MDEs) were anemia in 11, anemia + bone disease in 4, and bone disease in 3 patients. Among patients with a bone disease MDE, 4/7 had &amp;gt;1 lytic lesions on imaging and 3 had vertebral compression fracture(s). No patient had renal insufficiency or hypercalcemia as MDE. The sole patient with SLiM had a serum free light chain ratio&amp;gt;100 as the only MDE. 13/102 patients (12.75%) died, with 4/13 deaths attributed to myeloma after disease progression. The predicted median 2-year risk of progression to MM with different risk-stratification models were as follows: PANGEA with Bone Marrow (BM): 5.75% (range, 1.2-42); PANGEA without BM: 4.6% (0.7-26.6); Mayo 20/2/20: 9.7% (9.7-47.4); IMWG SMM: 26% (3.8-73). Figure 2 shows Sankey diagram of predicted risk tertiles for patients at SMM diagnosis by different models. Notably, a substantial proportion of high-risk patients by 20/2/20, who are currently considered for therapeutic intervention, were re-assigned to intermediate risk (2-year risk of progression 8.1-20%) by PANGEA-BM. Conclusion: The risk of progression to MM among this cohort of contemporary patients with SMM is &amp;lt;5% per year for the 1 st 4 years, which is substantially lower than the historical rate of 10% per year. Morbid progression such as renal failure or fractures are very infrequent, with anemia being the most common MDE. Prospective studies testing active surveillance strategies are needed in contemporary SMM cohorts to determine the optimal approach to these patients and ensure balancing of potential risks and benefits of treatment.

Optimum Fermentation Conditions for Bovine Lactoferricin-Lactoferrampin-Encoding LimosiLactobacillus reuteri and Regulation of Intestinal Inflammation.

The multifunctional antibacterial peptide lactoferricin-lactoferrampin (LFCA) is derived from bovine lactoferrin. Optimization of the fermentation process should be studied since different microorganisms have their own favorable conditions and processes for growth and the production of metabolites. In this study, the culture conditions of a recombinant strain, pPG-LFCA-E/LR-CO21 (LR-LFCA), expressing LFCA was optimized, utilizing the high-density fermentation process to augment the biomass of LimosiLactobacillus reuteri and the expression of LFCA. Furthermore, an assessment of the protective effect of LR-LFCA on intestinal inflammation induced by lipopolysaccharide (LPS) was conducted to evaluate the impact of LR-LFCA on the disease resistance of piglets. The findings of this study indicate that LR-LFCA fermentation conditions optimally include 2% inoculation volume, 36.5 °C fermentation temperature, 9% dissolved oxygen concentration, 200 revolutions/minute stirring speed, pH 6, 10 mL/h glucose flow, and 50% glucose concentration. The inclusion of fermented LR-LFCA in the diet resulted in an elevation of immunoglobulin levels, significant upregulation of tight junction proteins ZO-1 and occludin, reinforcement of the intestinal barrier function, and significant amelioration of the aberrant alterations in blood physiological parameters induced by LPS. These results offer a theoretical framework for the implementation of this micro-ecological preparation in the field of piglet production to enhance intestinal well-being.

Guillain-Barré Syndrome Following Spinal Fusion Surgery in an Elderly Patient: A Case Report

Guillain–Barré syndrome (GBS) is a rare immune-mediated polyneuropathy that rapidly leads to symmetric, ascending progressive weakness. Although GBS is typically associated with various infectious diseases, such as upper respiratory infections or gastroenteritis, it has also been reported following spine surgery. In this report, the authors present a case of GBS in an elderly patient after spinal fusion surgery and emphasize the importance of evaluating new-onset weakness in such cases. A 79-year-old man with diabetes mellitus and hypertension presented with weakness of the lower extremities and neurogenic claudication with chronic radicular pain. Magnetic resonance imaging revealed anterolisthesis at the L4-L5 level and disc protrusions with central and lateral recess spinal stenosis at L3-L4-L5. Following surgery, the patient complained of weakness and paresthesia in both upper extremities, prompting further investigation. An electrophysiologic study confirmed demyelinating neuropathy and cerebrospinal fluid (CSF) analysis showed elevated viral immunoglobulin levels and albumin-cytological dissociation despite negative bacterial and antiganglioside antibody tests. The patient received intravenous immunoglobulin infusion treatment and showed significant improvement, with full motor function recovery in all extremities after 6 weeks. The authors emphasize the importance of considering GBS in patients experiencing deteriorating neurological symptoms after spine surgery and suggest that electrophysiologic studies and CSF analysis are needed for an accurate diagnosis. Additionally, this report highlights the need for increased vigilance regarding the rapid onset of GBS symptoms in elderly patients following spinal surgery.

Fungal microbiota sustains lasting immune activation of neutrophils and their progenitors in severe COVID-19.

Gastrointestinal fungal dysbiosis is a hallmark of several diseases marked by systemic immune activation. Whether persistent pathobiont colonization during immune alterations and impaired gut barrier function has a durable impact on host immunity is unknown. We found that elevated levels of Candida albicans immunoglobulin G (IgG) antibodies marked patients with severe COVID-19 (sCOVID-19) who had intestinal Candida overgrowth, mycobiota dysbiosis and systemic neutrophilia. Analysis of hematopoietic stem cell progenitors in sCOVID-19 revealed transcriptional changes in antifungal immunity pathways and reprogramming of granulocyte myeloid progenitors (GMPs) for up to a year. Mice colonized with C. albicans patient isolates experienced increased lung neutrophilia and pulmonary NETosis during severe acute respiratory syndrome coronavirus-2 infection, which were partially resolved with antifungal treatment or by interleukin-6 receptor blockade. sCOVID-19 patients treated with tocilizumab experienced sustained reductions in C. albicans IgG antibodies titers and GMP transcriptional changes. These findings suggest that gut fungal pathobionts may contribute to immune activation during inflammatory diseases, offering potential mycobiota-immune therapeutic strategies for sCOVID-19 with prolonged symptoms.

Effects of Anticoccidial Vaccination and Taraxacum officinale Extract on the Growth Performance, Biochemical Parameters, Immunity, and Intestinal Morphology of Eimeria-Challenged Chickens.

A total of 160 Ross 308 male chickens were used in a 2 × 2 factorial design to examine the effects of anticoccidial vaccination (ACV; lack or 1× dose recommended by the manufacturer) and dietary supplementation with Taraxacum officinale (dandelion) extract (DE; with or without) on growth performance, immunity, biochemical parameters, and intestinal morphology in broiler chickens challenged with Eimeria spp. At 20 days of age, all birds were challenged with a 25× dose of ACV, including Eimeria acervulina, E. maxima, E. mitis, and E. tenella. No interaction between ACV and DE was observed in terms of growth performance. Vaccinated birds showed increased feed intake (FI) and feed conversion ratio (FCR) during the 11-20 day period. Meanwhile, DE supplementation led to decreased FI and body weight gain (BWG) during the 1-10 day period. ACV effectively induced immunity against Eimeria, as evidenced by reduced oocyst shedding and less intestinal lesions, decreased levels of pro-inflammatory interleukin-6, and improved BWG during both the post infection (PI) period (21-35 days) and the entire growth period. DE supplementation lowered FCR and increased BWG during the 35-42 day period, increased the concentration of butyric acid in the cecal digesta, and lowered oocyst shedding PI. In vaccinated birds, DE elevated levels of plasma total protein and immunoglobulin M, and influenced tight junction proteins zonula occludens-1 and claudin-3, indicating a more robust epithelial barrier. DE also lowered alanine aminotransferase activity in unvaccinated birds. Both ACV and DE independently improved intestinal morphology in the jejunum, decreasing crypt depth and increasing the villus height-to-crypt ratio. These findings suggest that both ACV and DE could be effective strategies for managing coccidiosis in broiler chickens.

Elevated serum levels of T-cell immunoglobulin and mucin-domain containing molecule 3 in patients with systemic inflammation following COVID-19 vaccination.

ChAdOx1 nCoV-19 vaccine has been widely used. Some unexpected adverse effects such as the development of systemic hyper inflammation with multiorgan involvement after vaccination, in rare cases, have been reported. However, its pathogenesis remains unclear. This study recruited two cases who suffered from systemic inflammation following ChAdOx1 nCoV-19 vaccine and two 30-year-old male volunteers without underlying disease who have received ChAdOx1 nCoV-19 vaccine as control group. Blood samples were collected from our patients and healthy subjects before and after treatment with anti-inflammatory agent such as glucocorticoid and tocilizumab. The immune profile from our patients and healthy controls were measured using a human XL cytokine Proteome Profiler array (ARY022b, R&D Systems). Biochemical parameters revealed leukocytosis with segmented neutrophil dominance and elevated serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate, and ferritin in these two patients. The cytokine array revealed that mean levels of T cell immunoglobulin and mucin-domain containing-3 (TIM-3) (3640.3 vs 1580.5 pixels per inch [ppi]), B-cell activating factor (BAFF) (3036.8 vs 1471.0 ppi), urokinase plasminogen activator surface receptor (uPAR) (1043.1 vs 516.8 ppi), Resistin (1783.7 vs 711.3 ppi), platelet-derived growth factor (PDGF)-AB/BB (1980.7 vs 939.7 ppi), macrophage inflammatory protein-3-beta (MIP-3β) (911.9 vs 346.2 ppi), and interferon-inducible T-cell alpha chemoattractant (I-TAC) (1026.3 vs 419.7 ppi) were 2-fold higher in the patients than in normal subjects who received ChAdOx1 nCoV-19 vaccine. We demonstrated that systemic inflammation may occur in subjects who have received the ChAdOx1 nCoV-19 vaccination. Moreover, we proposed immune markers, which may be implicated in the pathogenesis of systemic inflammation following COVID-19 vaccination as potential diagnostic biomarkers.

Case Report: Spontaneous pneumothorax revealing multiple myeloma: a case report

Various causes like trauma, infection, pulmonary disease or neoplasm can lead to spontaneous pneumothorax. We report a rare case of a spontaneous pneumothorax as first manifestation of multiple myeloma. A 58-year-old patient presented suffering from dyspnea and right-sided chest pain, with no history of trauma. On examination, the patient had bilateral rib tenderness. The respiratory rate was 30 breaths/min and oxygen saturation was 88%. The chest physical exam revealed unequal breath sounds, an hyperresonance with percussion and decreased wall movement on the right side. The analysis of arterial blood gas revealed hypoxemia (arterial oxygen tension: 7.59 kPa) and hypercapnia (arterial carbon dioxide tension: 5.99 kPa). Laboratory data showed a raised C reactive protein level (133.8 mg/L), hyper-calcemia (serum calcium: 12.18 mg/dL) and a decreased plasma albumin level (31.9 g/L). Chest radiography and thoracic computed tomography revealed multiple ribs and sternum fractures leading to a partial pneumothorax on the right side. Subsequent workup for multiple myeloma showed elevated levels of immunoglobulin. Results of initial laboratory tests revealed an IgG gamma paraprotein, a urine protein electrophoresis of 1450 mg/24 hours and a β-2 microglobulin rate of 3.35. The diagnosis of multiple myeloma was confirmed with a bone marrow infiltration of 20% of atypical plasmatic cells. Cytogenetic investigations did not show any chromosomal abnormalities, especially the t (4,14) translocation. The patient was diagnosed with multiple myeloma stage IIIA according to Durie–Salmon classification. Appropriate treatment with oxygen therapy and systemic analgesic was started, associated with a cure of zoledronic acid in order to decrease the calcium level. The evolution was characterized by the complete resolution of the pneumothorax in 7 days and the normalization of the calcium level. The autologous stem cell transplant was the treatment of choice for this patient.

Leukocyte associated immunoglobulin-like receptor 1 modulates immune response to Staphylococcus aureusinfection

Abstract Immunity is a balance of maximal pathogen defense with minimal host damage. Inhibitory immune receptors are important for maintaining this balance. We recently identified elevated levels of leukocyte-associated immunoglobulin (Ig)-like receptor protein1 (LAIR1), an inhibitory immune receptor, in cutaneous lymphoma patients, in whom invasive Staphylococcus aureus (S. aureus) infections are frequent. We therefore tested Lair1 knock-out (KO) mice in two models of invasive S. aureus infection: pneumonia and subcutaneous skin infection. In WT mice, skin infections resolve by 14 days post-infection (dpi), while pneumonia infections cause &amp;gt;50% lethality by 2dpi. In both models, Lair1 KO mice showed consistent patterns of myeloid hyper-activation. Lair1 KO had consistently larger skin lesions than WT throughout the 14 days, but no difference in bacterial clearance. Lair1 KO with pneumonia had higher survival (100% KO vs. 33% WT) despite comparable measures of lung injury and immune cell recruitment. In both models, KO mice produced higher levels of proinflammatory cytokines (IL-6, IL-1b) and neutrophil chemokines (CCL2, 3, 4) in lung, bronchoalveolar lavage, and skin by multiplex cytokine array. KO bone marrow-derived macrophages infected with S. aureus in vitro also secreted higher levels of proinflammatory cytokines (IL-6) and neutrophil chemokines (CCL2, 3, 4). Together, our results demonstrate that LAIR1 loss enhances myeloid activation, resulting in excessive tissue damage in skin infection, yet is protective against death in pneumonia. We posit that LAIR1 plays a crucial role in balancing myeloid immune response; LAIR1 activity can be beneficial or detrimental to the host depending on the site and type of infection.