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Immunoglobulin (Ig) A supports mucosal immune homeostasis and host-microbiota interactions. While commensal bacteria are known for their ability to promote IgA, the role of non-bacterial commensal microbes in the induction of IgA remains elusive. Here, we demonstrate that permanent colonization with the protozoan commensal Tritrichomonas musculis (T.mu) promotes T cell-dependent, IgA class-switch recombination, and intestinal accumulation of IgA-secreting plasma cells (PC). T.mu colonization specifically drives the expansion of T follicular helper cells and a unique ICOS+ non-Tfh cell population, accompanied by an increase in germinal center B cells. Blockade of ICOS:ICOSL co-stimulation or MHCII-expression on B cells is central for the induction of IgA following colonization by T.mu, implicating a previously underappreciated mode of IgA induction following protozoan commensal colonization. Finally, T.mu further improves the induction of IgA-secreting PC specific to orally ingested antigens and their peripheral dissemination, identifying T.mu as a natural adjuvant for IgA. Collectively, these findings propose a protozoa-driven mode of IgA induction to support intestinal immune homeostasis.

ObjectivePrimary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva.MethodsUsing a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls.ResultsSaliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

Peyers patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses that give rise to many intestinal IgA-secreting cells. Induction of isotype switching to IgA in PPs requires interactions between B cells and TGFβ-activating conventional dendritic cells type 2 (cDC2s) in the subepithelial dome (SED). However, the mechanisms promoting cDC2 positioning in the SED are unclear. Here, we found that PP cDC2s express GPR35, a receptor that promotes cell migration in response to various metabolites, including 5-hydroxyindoleacetic acid (5-HIAA). In mice lacking GPR35, fewer cDC2s were found in the SED, and frequencies of IgA+ germinal center (GC) B cells were reduced. IgA plasma cells were reduced in both the PPs and lamina propria. These phenotypes were also observed in chimeric mice that lacked GPR35 selectively in cDCs. GPR35 deficiency led to reduced coating of commensal bacteria with IgA and reduced IgA responses to cholera toxin. Mast cells were present in the SED, and mast cell-deficient mice had reduced PP cDC2s and IgA+ cells. Ablation of tryptophan hydroxylase 1 (Tph1) in mast cells to prevent their production of 5-HIAA similarly led to reduced PP cDC2s and IgA responses. Thus, mast cell-guided positioning of GPR35+ cDC2s in the PP SED supports induction of intestinal IgA responses.

Simple Summary: Increasing the immunoglobulin A (IgA) potential of sow colostrum protects newborn piglets against infection during the pre- and post-weaning periods. Feeding pigs with multi-species probiotics (5 g/sow/day) via top dressing from 4 weeks before farrowing until weaning increases the IgA levels in colostrum during the first 6 h after farrowing. This subsequently improved the piglets' weaning weight and reduced the pre-weaning mortality rate in an outbreak breeder herd with porcine epidemic diarrhea (PED). The aim of the present study was to investigate the potential of a multi-species probiotics product to promote IgA-containing-colostrum production in sows during 24 h of lactation and subsequently promote piglet growth and diminish the pre-weaning mortality rate in a porcine epidemic diarrhea (PED)-infected herd. Sows in the 12th week of pregnancy (n = 20) with an average parity number of 2.4 ± 1.4 were divided into two groups: untreated control and probiotic-supplemented groups (treatment). They received a treatment composed of basal feed with a probiotic (5 g/sow/day) via top dressing from the 12th week of pregnancy until weaning. Colostrum samples were collected at 3, 6, 12, 24, and 48 h, and the Immunoglobulin A (IgA) levels were measured by using an ELISA kit. The weaning weight and pre-weaning mortality rate were recorded. There was a significantly higher level of IgA in the treatment group than there was in the control one (p < 0.001). In the treatment group, the highest level of IgA was found at 6 h (26.22 mg/mL), and the lowest level was found at 48 h (4.51 mg/mL). In the control group, the highest level of IgA level was found at 3 h (16.16 mg/mL), and the lowest level was found at 3 h (3.41 mg/mL). The treatment-administered pigs had a significantly higher (p < 0.05) weaning weight (5.90 kg/pig) when compared with that of the control pigs (3.90 kg/pig). A lower pre-weaning mortality rate (24.90%) was found in the treatment group when compared with that of the control pigs (53.60%) (p < 0.05). In conclusion, multi-species probiotic supplementation in sows increases the IgA level in colostrum during the first 6 h after farrowing, subsequently improving the weaning weight and reducing the pre-weaning mortality rate during porcine epidemic diarrhea (PED) outbreaks. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, there has been a severe shortage of crude protein feed resources for ruminants due to the rapid growth of the animal industry, with traditional feed resources such as alfalfa and soybean meal unable to meet this challenge because of production and price factors. Therefore, it is necessary to explore alternative protein feed resources. Broussonetia papyrifera silage, as a non-conventional protein feed resource, has significant potential. Thus, this study evaluated the effectiveness of Broussonetia papyrifera silage feed for ruminants by investigating its effect on the growth performance, blood parameters, immune response, antioxidant function, and rumen microbial community composition of Kazakh lamb. The findings indicate that Broussonetia papyrifera silage does not adversely affect the growth performance of these lambs; instead, it shows promise in enhancing immune response and antioxidant capacity while promoting a balanced rumen microbial ecology. Numerous studies have demonstrated that Broussonetia papyrifera is an unconventional feed resource with significant developmental potential. This research aimed to explore the effects of Broussonetia papyrifera silage on the growth performance, blood parameters, immunity, antioxidation, cytokine levels, and rumen bacterial composition of Kazakh lamb. Forty healthy male Kazakh lambs, aged 5 months and weighing 30.12 ± 1.14 kg, were randomly divided into control and experimental groups, each consisting of four replicates (five lambs per replicate). The control group was fed a basal diet, while the experimental group received a diet supplemented with 20% Broussonetia papyrifera silage (dry matter basis). Following a 10-day pre-feeding period, a 60-day formal experiment was conducted. The results indicated no significant difference in growth performance between the experimental and control groups. However, compared to the control group, the use of Broussonetia papyrifera silage significantly reduced (p < 0.05) neutrophil, lymphocyte, and eosinophil counts, as well as creatinine levels in the blood. Furthermore, Broussonetia papyrifera silage (p < 0.01) enhanced total serum antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase, immunoglobulin A, immunoglobulin M, immunoglobulin G, interleukin-2, interleukin-6, and interleukin-8, and decreased malondialdehyde and interleukin-4 levels. Additionally, the use of Broussonetia papyrifera silage increased the diversity and richness of the rumen bacterial community, notably enhancing the relative abundance of Firmicutes such as Rikenellaceae_RC9_gut_group and Christensenellaceae_R-7_group. In conclusion, feeding Kazakh lamb with Broussonetia papyrifera silage (20% DM) did not adversely affect their growth performance but improved their immunity and antioxidant capacity and enhanced the relative abundance of beneficial bacteria in the rumen, thereby promoting animal health. [ABSTRACT FROM AUTHOR]

The kappa index is a well-established marker of intrathecal synthesis (IS) of immunoglobulin (Ig). Routinely used for diagnostic aims, IgG IS, which can be assessed quantitatively (ad hoc formulas) or qualitatively (oligoclonal bands, OCBs), may fail in detecting a humoral immune response within the central nervous system (CNS). The main aim of this study was to evaluate the kappa index for its ability to detect the presence of CNS humoral immunity and to associate it with a distinct group of disorders, in the absence of IgG IS/OCBs. Within the kappa index-positive, IgG OCB-negative (Kappa+OCB-) patient group, we also examined whether IgM/IgA IS, determined with the IgM/IgA index and CSF IgM OCBs, could contribute to disease group stratification. Diagnoses were classified as multiple sclerosis (MS), or other inflammatory (INFL), infectious (INFECT), or non-inflammatory (Other) central/peripheral nervous system disorders. Sixty-nine Kappa+OCB- patients and 50 controls (24 Kappa-OCB- and 26 Kappa+OCB+ patients) were included in this study. The most frequent diagnosis in the Kappa+OCB- group was MS (27/69), followed by INFECT (16/69). Additional evidence of IS was demonstrated through an elevated IgG/IgM/IgA index or by the presence of IgM OCBs in 59%, and through only IgM/IgA IS in 52% of cases. In INFECT patients, the median IgM/IgA indexes were higher (p < 0.001) than in other groups, with 18 patients (95%) presenting an elevated IgM index, 11 patients (58%) presenting CSF IgM OCBs, and 10 patients (53%) presenting an elevated IgA index. The vast majority of all INFECT (16/19) belonged to the Kappa+OCB- group. Our data confirm that the kappa index performs at the highest level in assessing intrathecal humoral immunity and supporting the diagnosis of both MS and CNS infectious disorders, which are also characterized by the intrathecal production of IgM and IgA. [ABSTRACT FROM AUTHOR]

Hyperviscosity syndrome (HVS) is defined as the symptomatic presentation of increased blood thickness due to various clinical conditions such as hypergammaglobulinemia. HVS secondary to immunoglobulin (Ig)A multiple myeloma has been infrequently reported. Although the efficiency of IgM or IgG removal by therapeutic plasma exchange (TPE) is well described, the efficiency of IgA removal by TPE is not as well known. Here, we describe a case of HVS due to IgA myeloma in a patient who received 2 TPE treatments, with subsequent symptomatic improvement as well as decrease in IgA and viscosity levels. [ABSTRACT FROM AUTHOR]

Common variable immune deficiency (CVID) with the frequency of 1 in 25000 is the "COMMON" form among the primary immunodeficiency diseases. It has a phenotype encompassing symptoms involving the lungs, gastrointestinal (GI) tract often, and joints. Symptoms are due to autoimmune and inflammatory reactions. These are seen from childhood to adult life with variable progression. Diagnostic criteria are defined now and include ruling out acquired hypogammaglobulinemia and agammaglobulinemia and include genetic testing. A higher incidence of cancer of the lymphoid or GI tract is reported. Treatment is the replacement of immunoglobulins. We report a patient with CVID with isolated GI symptoms. CVID is a less suspected, less recognized disease in India. Isolated GI symptoms in the form of diarrhea with no sinopulmonary and other organ involvement are even more, less common. [ABSTRACT FROM AUTHOR]

In the diagnosis of linear IgA bullous dermatosis (LABD), detection of IgA at the epidermal basement membrane zone and circulating IgA autoantibodies are essential. The disease has two subtypes, lamina lucida-type and sublamina densa-type, with 120 kDa LAD-1 and 97 kDa LABD97 as major autoantigens for lamina lucida-type. Normal human epidermal keratinocytes (NHEK) and HaCaT cells are widely used for immunoblotting (IB) in the diagnosis process, but they do not provide high sensitivity and semiquantitative analysis. To develop a more sensitive and convenient method for detecting IgA antibodies in lamina lucida-type LABD patients. The expressions of LAD-1 and LABD97 in lysates and culture supernatants from Ker-CT, HaCaT, DJM-1, and NHEK were compared. The sensitivity of IBs using concentrated culture supernatants of HaCaT and Ker-CT and ELISAs using several recombinant proteins (RPs) corresponding to BP180 ectodomain were compared using 55 sera from LABD patients. In culture supernatant, Ker-CT expressed higher amounts of LAD-1 and LABD97. IBs using concentrated culture supernatant of HaCaT and Ker-CT showed 43 % and 46 % positivity to sera from LABD patients, respectively. In ELISAs, the RP of amino acids 490–1421 of BP180 showed the highest positivity (80.0 %) among several proteins. Additionally, this ELISA showed reduced OD values in LABD and related diseases patients' sera at remission. The ELISA using the RP coding amino acids 490–1421 of BP180 is useful for identifying IgA antibodies and monitoring disease activity in lamina lucida-type LABD patients. ● Ker-CT is a better cell line to collect BP180 and its shedding proteins, LAD-1 and LABD97. ● Immunoblotting of Ker-CT shows more intelligible bands than that of HaCaT cells. ● The ELISA for amino acids 490–1421 of BP180 is useful for diagnosis of LABD. [ABSTRACT FROM AUTHOR]

To prevent infection, the experience of the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic has led to recognition of the importance of not only vaccines but also the strengthening of mucosal barriers by secretory immunoglobulin A (IgA). Strong mucosal barrier provided by IgA is also possible to prevent allergies and chronic inflammatory conditions in the intestinal tract, since it can protect foreign enemies or antigens at the first line of defense before their invasion. Therefore, it is important to understand the role of IgA antibodies secreted by the mucosa of the body. In this section, we discuss the role of mucosal IgA antibodies in relation to three disease states: control of intestinal microbiota, protection against infection, and allergy. In addition, we provide the evidence in which the quality as well as the quantity of IgA is critical for disease prevention. Therefore, we discuss about novel strategies to enhance mucosal barriers by induction of high-quality IgA. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusion The objective of this study is to evaluate the therapeutic effect of conservative treatment in children with juvenile recurrent parotitis (JRP).Clinical data from 55 children who were diagnosed with JRP from June 2019 to January 2022 were collected. On admission, patients underwent comprehensive examinations, and a questionnaire was completed by the patients and their parents. Patients received only conservative treatment, including sialagogues, warm compresses, massage and antibiotic treatment.Episodes after treatment (1.11 ± 1.42) were significantly lower in 55 patients than before treatment (3.35 ± 2.42) (p < 0.001). Clinical symptoms improved for 81.81% and recurred for 60%. Patients who did not respond to treatment were in 3‐ to 5‐year‐old group. The serum IgG (p = 0.018), IgA (p = 0.014) and IgM (p = 0.032) levels in the nonresponsive group were significantly higher than those in the improvement group and were either higher than the normal range or at the upper limit. The improvement rate was positively related to the CD8%, and the serum IgA concentration was negatively related to the number of previsit episodes.Conservative treatment is effective for most children with JRP. Patient responses to treatment may be associated with the maturation of their immune systems. Underlying immune dysregulation should be evaluated, and further treatment is needed in severe cases. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusion Food protein‐induced enterocolitis syndrome (FPIES) is a non‐IgE‐mediated allergy without known biomarkers. We aimed to compare fecal biomarkers related to gut inflammation and immunity in children with FPIES, with resolved FPIES (tolerant), and in matched controls.Stools were collected from FPIES children on elimination diet, before and after an oral food challenge (OFC) performed to assess their natural tolerance, at the end of a follow‐up in tolerant FPIES children, and in matched controls (1:1 ratio). Concentrations of calprotectin, EDN (eosinophilic derived neurotoxin), and secretory IgA (sIgA) underwent comparative paired analysis.Thirty‐eight patients were included (age: 1.3 years old, interquartile range: IQR [0.9–2.0]), of which 22 became tolerant during follow‐up. Upon inclusion, allergic patients and controls had similar concentrations of calprotectin (38 μg/g [8–85] vs. 27 μg/g [11–46], p = 0.15) and EDN (504 ng/g [275–1252] vs. 516 ng/g [215–844], p = 0.86). However, concentrations of these inflammatory biomarkers increased transiently after a failed OFC (p < 0.001 and p = 0.01 respectively), without correlating with the severity of an allergic reaction. sIgA were higher in allergic than in tolerant patients: 2224 μg/g [878–3529] vs. 794 μg/g [699–1767] (p < 0.01). Calprotectin, EDN, and sIgA were comparable in tolerant patients and controls. sIgA less than 2637 μg/g had a negative predictive value of 75.3% for the differentiation allergic patients from tolerant patients and controls (area under curve: 0.63, 95% CI: 0.52–0.74).A few days after an acute allergic reaction, there was no detectable chronic gut inflammation in FPIES. sIgA may be a useful tool for clinicians in timing OFC. [ABSTRACT FROM AUTHOR]

Existing parenteral SARS‐CoV‐2 vaccines produce only limited mucosal responses, essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters can overcome the shortcomings of parenteral vaccines and enhance pre‐existing systemic immunity. Here, a new protein subunit nanovaccine is developed by utilizing dual‐adjuvanted (RIG‐I: PUUC RNA and TLR‐9: CpG DNA) polysaccharide‐amino acid‐lipid nanoparticles (PAL‐NPs) along with SARS‐CoV‐2 S1 trimer protein, that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal‐systemic SARS‐CoV‐2 immunity. Mice receiving IM‐Prime PUUC+CpG PAL subunit nanovaccine, followed by an IN‐Boost, developed high levels of IgA, IgG, and cellular immunity in the lungs and showed robust systemic humoral immunity. Interestingly, as a purely intranasal subunit vaccine (IN‐Prime/IN‐Boost), PUUC+CpG PAL‐NPs induced stronger lung‐specific T cell immunity than IM‐Prime/IN‐Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS‐CoV‐2 vaccination may also be feasible. The data suggest that PUUC+CpG PAL subunit nanovaccine is a promising candidate for generating SARS‐CoV‐2 specific mucosal immunity. [ABSTRACT FROM AUTHOR]

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Background/Objectives: In a previous study, we described elevated anti-Anisakis IgG levels in septic patients in relation to disease severity. In this study, our objective was to analyze the evolution of anti-Anisakis immunoglobulins in septic patients during hospital admission and their association with αβ and γδ T cell subsets. Methods: We recruited 80 subjects: 40 patients with sepsis and 40 controls. αβ and γδ T cells were analyzed using flow cytometry. Apoptosis was also assessed, and anti-Anisakis antibodies were measured by ELISA in the sera of patients with sepsis and controls. Results: In the second analysis (7–10 after sepsis evolution), an increase in all specific antibody isotypes was identified in individuals with septic shock, except IgE. The levels of anti-Anisakis IgG and IgA were higher in the subjects with sepsis in the first analysis and continued to increase in the second analysis compared with the healthy control subjects. There was an increase in anti-Anisakis IgG and IgA levels in surviving patients and an increase in IgA levels in non-surviving patients. A rise in specific IgG and IgE levels was noted in the second analysis of patients with sepsis with αβ CD3+ T cell deficiency. Patients without γδ T cell deficiency had increased anti-Anisakis IgA levels 7–10 days after admission. Conclusions: Our results suggest a previous infection by Anisakis that could be involved in the subsequent septic process and be related to patients who have negative cultures in which the pathogen causing sepsis has not been identified. [ABSTRACT FROM AUTHOR]

Background/Objectives: Schizophrenia (SZ) is a complex psychiatric disorder with increasing evidence pointing to an autoimmune component, including the presence of antiphospholipid antibodies (aPLs). This study aims to assess the prevalence of anticardiolipin (aCL) and anti-beta-2 glycoprotein I (aβ2GPI) antibodies, particularly the IgG, IgA, and IgM isotypes, in drug-free SZ patients compared to healthy controls, and explore their possible involvement in the disease's pathophysiology. Methods: Eighty SZ patients meeting DSM-IV criteria were recruited, along with 80 matched healthy controls. Serum samples were analyzed using enzyme-linked immunosorbent assays (ELISA) to quantify IgG, IgA, and IgM isotypes of aCL and aβ2GPI. Results: SZ patients exhibited significantly higher levels of aCL-IgM and aCL-IgA (p < 0.05), as well as elevated aβ2GPI-IgA (22.5%, p < 0.001), compared to controls. No significant differences were observed in the aCL-IgG isotype. Interestingly, 72% of aPL-positive SZ patients were positive for aβ2GPI-IgA, with some also co-expressing multiple isotypes, suggesting a potential link between SZ and antiphospholipid syndrome (APS). Conclusions: This study is the first to report a high prevalence of aCL-IgA and aβ2GPI-IgA in SZ patients, highlighting a possible autoimmune involvement in the disease. The presence of multiple aPL isotypes, particularly IgA, suggests a need for further investigation into their role in SZ pathogenesis and their potential association with APS. [ABSTRACT FROM AUTHOR]

The progression of monoclonal gammopathies is affected by a range of factors, including the microenvironment surrounding plasma cells. It is recognized that TGF‐β1 plays a distinct role in stimulating IgA production. Hence, this study aims to investigate whether individuals with serum IgA monoclonal immunoglobulins (paraproteins) exhibit elevated total TGF‐β1 levels compared to those with IgG or IgM paraproteins. To achieve this goal, individuals with a positive laboratory finding of monoclonal gammopathy were segregated according to the paraprotein class as well as according to the type of the light chain. Total TGF‐β1 levels were assessed in blood serum samples containing IgG (n = 50), IgA (n = 46), and IgM (n = 31) paraproteins. Elevated level of TGF‐β1 was confirmed in sera with IgA paraproteins (median 25.8 ng/mL; interquartile range IQR: 19.0–33.7) compared to those having IgG (median: 18.2 ng/mL; IQR: 14.3–22.1; p < 0.001) or IgM paraproteins (21.5 ng/mL; IQR: 15.0–27.4; p = 0.043). Also, a higher TGF‐β1 level was detected in sera with IgMλ than those with IgMκ paraproteins (p = 0.043). This research affirms the role of TGF‐β1 in the pathophysiology of IgA monoclonal gammopathies and the potential switch towards the IgA isotype, known for a less favourable prognosis. [ABSTRACT FROM AUTHOR]

In recent years, there has been increasing attention towards understanding the relationship between age‐related alterations in the oral microbiota and age‐associated diseases, with reports emphasizing the significance of maintaining a balanced oral microbiota for host health. However, the precise mechanisms underlying age‐related changes in the oral microbiota remain elusive. We recently reported that cellular senescence of ileal germinal center (GC) B cells, triggered by the persistent presence of commensal bacteria, results in diminished IgA production with aging and subsequent alterations in the gut microbiota. Consequently, we hypothesize that a similar phenomenon may occur in the oral cavity, potentially contributing to age‐related changes in the oral microbiota. Examination of p16‐luc mice, wherein the expression of the senescent cell marker p16INK4a can be visualized, raised under specific pathogen‐free (SPF) or germ‐free (GF) conditions, indicated that, unlike ileal GC B cells, the accumulation of senescent cells in GC B cells of cervical lymph nodes increases with age regardless of the presence of commensal bacteria. Furthermore, longitudinal studies utilizing the same individual mice throughout their lifespan revealed concurrent age‐related alterations in the composition of the oral microbiota and a decline in salivary IgA secretion. Further investigation involving Rag1−/− mice transplanted with B cells from wild‐type or p16INK4a and p21Waf1/Cip1 ‐double knockout mice unveiled that B cell senescence leads to reduced IgA secretion and alteration of the oral microbiota. These findings advance our understanding of the mechanism of age‐associated changes in the oral microbiota and open up possibilities of their control. [ABSTRACT FROM AUTHOR]

Background: Data on the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in China are very limited. Our aim was to determine the prevalence and clinical characteristics of MGUS in a large Chinese population. Methods: This study included 49,220 healthy people who received serum immunofixation electrophoresis (sIFE) and serum protein electrophoresis (SPE) tests. Serum free light chain ratio, immunoglobulin quantification, and other clinically correlates of MGUS were performed for all patients with M-protein. Results: A total of 576 MGUS patients were identified by sIFE, with a median age of 58 years and an overall prevalence of 1.17% (95% CI, 1.08–1.27). Among those aged 50 years and older, the prevalence of MGUS was 2.26% (95% CI, 2.04–2.50). The prevalence of MGUS was significantly higher in males than in females (P < 0.05). The median concentration of M-protein was 3.1 g/L, ranging from 0.5 g/L to 25.1 g/L. The M-protein type was IgG in 55.4% of MGUS patients, followed by IgA (31.1%), IgM (9.5%), IgD (0.5%), biclonal (2.3%), and light chain (1.2%). Abnormalities in SPE, FLC ratios, and immunoglobulin levels were observed in 78.3%, 31.1%, and 38.4% of MGUS patients, respectively. Conclusions: The prevalence of MGUS is substantially lower in southern China than in whites and blacks. [ABSTRACT FROM AUTHOR]

Introduction: Topical therapies are used in almost all patients with psoriasis. A novel fixed topical combination cream (GN-037) with a lower concentration (0.0356%) of clobetasol 17-propionate (CP) was developed together with urea, salicylic acid, and retinoic acid to provide a better benefit–risk ratio. The present multicenter randomized double-blind vehicle-controlled parallel group phase 2 study aimed to investigate the efficacy and safety of GN-037 in patients with mild-to-moderate plaque psoriasis (MMPP). Methods: Patients (n = 190) were randomized (2:2:1) to receive GN-037 or CP or vehicle (V) cream twice daily to a selected target body lesion for 4 weeks. The primary endpoint was treatment success defined as percentage of patients with at least two-grade improvement in Investigator's Global Assessment Score (IGA) and IGA score equal to 0 or 1 evaluated at weeks 2, 4, 6, and 8 in each arm compared with baseline. Treatment-emergent adverse events (TEAEs) and safety were evaluated throughout the study. Results: GN-037 demonstrated statistically significant superiority over V throughout the study. At week 4, treatment success was achieved in 37.9% of patients in the GN-037 arm compared with 29.2% and 9.1% in the CP and V arms, respectively. At least two-grade improvement compared with baseline was achieved by 57.6%, 72.7%, and 80.3% of the patients in the GN-037 arm for erythema, plaque elevation, and scaling, respectively. The mean changes in affected BSA were −2.1 ± 2.9, −1.8 ± 2.4, and −0.5 ± 1.6 in the GN-037, CP, and V arms, respectively. The TEAEs were similar among the arms and the most frequently observed TEAEs were Psoriasis Area and Severity Index (PASI) increase in all arms. Conclusions: GN-037 was more effective than V in achieving primary and all secondary endpoints throughout the study. Safety data did not reveal any new safety concerns with the combination cream product. Therefore, 4 weeks of GN-037 treatment demonstrated an excellent efficacy and safety profile in patients with MMPP. Trial Registration number: ClinicalTrials.gov identifier, NCT05706870. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis in high-impact areas, including the scalp, nails, palms, and soles, can disproportionately impair patient quality of life. Here, we evaluate the 2-year efficacy of bimekizumab treatment in patients with moderate to severe plaque psoriasis in post hoc analyses of five phase 3/3b trials. Methods: High-impact area efficacy data were pooled through 2 years across five phase 3/3b trials: BE VIVID, BE READY, BE SURE, their ongoing open-label extension (OLE) BE BRIGHT, and BE RADIANT (including its double-blinded treatment period and the first year of its OLE). Complete clearance of psoriasis in high-impact areas is reported over 2 years using the scalp Investigator's Global Assessment (IGA), palmoplantar IGA, and modified Nail Psoriasis Severity Index (mNAPSI). Patients included in these analyses had baseline moderate to severe scalp or palmoplantar involvement (scalp or palmoplantar IGA score ≥ 3) or mNAPSI score > 10. Results: A total of 1107 patients were randomized to bimekizumab and entered the OLEs. Subsets of 821 patients had scalp IGA ≥ 3 at baseline, 377 had mNAPSI > 10, and 193 had palmoplantar IGA ≥ 3. Complete scalp clearance in patients with baseline scalp IGA ≥ 3 randomized to bimekizumab was achieved rapidly, with high responses sustained from first (86.4%) to second year (85.9%). Nail clearance responses in patients with baseline mNAPSI > 10 increased from 63.4% to 68.5% from first to second year. Palmoplantar clearance in patients with baseline palmoplantar IGA ≥ 3 was sustained from first (88.3%) to second year (89.8%). Similar trends were seen in the 374 patients who received bimekizumab 320 mg every 4 weeks (Q4W)/every 8 weeks (Q8W) initial/maintenance dosing. Conclusion: In these analyses pooled across 2 years, bimekizumab showed sustained efficacy in psoriasis in high-impact areas. Clinicaltrials.gov Trial Registration Numbers: NCT03370133, NCT03410992, NCT03412747, NCT03598790, NCT03536884. Plain Language Summary: Psoriasis in some body areas can have a bigger impact on the self-confidence and well-being of patients. These body areas, called high-impact areas, are often very visible or important for day-to-day activities. They include the scalp, fingernails, palms, and soles of the feet. People with psoriasis often find applying creams or ointments to these areas challenging. The treatment may also not be effective. Therefore, new medications that can clear psoriasis from these areas are needed by patients and physicians. Bimekizumab is a drug given by injection. We examined whether bimekizumab can clear psoriasis in high-impact areas over 2 years in five clinical trials. Psoriasis of the scalp, palms, and soles cleared quickly with bimekizumab. Most patients reported clear skin in these areas after 4 months, and skin remained clear for the rest of the 2-year period. After 2 years, 90% (18 in 20) of patients with psoriasis on their palms and soles saw it clear completely; 86% of patients (around 17 in 20) saw their scalp psoriasis completely cleared. Nail psoriasis took slightly longer to clear, because nails grow more slowly. Nevertheless, 63% of patients (around 13 in 20) had completely clear nails after 1 year and 69% of patients (around 14 in 20) had clear nails after 2 years. Bimekizumab can clear psoriasis in high-impact areas quickly, and this is maintained over the long-term. Bimekizumab can provide a lasting treatment option for areas of the body which are difficult to treat and have a big impact on patients' lives. [ABSTRACT FROM AUTHOR]

Simple Summary: 25-hydroxycholecalciferol has been widely used to increase the calcium and phosphorus absorption in lactating sows, while there have been only a few studies focusing on its effect on performance and health status of gestating sows and their offsprings. In this study, the dietary 25-hydroxycholecalciferol supplementation from day 85 of gestation was shown to effectively enhance the performance, antioxidant capacity, and immunoglobulin levels in sows and newborn piglets, which demonstrated that 25-hydroxycholecalciferol was an efficient additive for improving the reproductive performance and immune-antioxidant status of gestating sows during production. In this study, the aim was to evaluate the effects of dietary 25-hydroxycholecalciferol supplementation from day 85 of gestation on performance, antioxidant capacity, and immunoglobulin level of sows and newborn piglets. On day 85 of gestation, forty Landrace × Yorkshire gestating sows (average body weight of 241 ± 6.8 kg; average parity of 3.47 ± 0.6) were allotted into two treatments (20 replicates per treatment) based on parity, body weight, and back fat thickness. From day 85 of gestation to farrowing, sows were fed a normal vitamin D3 diet as control (containing 50 μg/kg vitamin D3; CON), or a 25-hydroxycholecalciferol-supplemented diet (containing 50 μg/kg 25-hydroxycholecalciferol). Compared with CON, dietary 25-hydroxycholecalciferol supplementation increased (p < 0.05) protein and fat content in colostrum and the average birth body weight of newborn piglets. Sows fed 25-hydroxycholecalciferol showed increased (p < 0.05) apparent total tract digestibility of crude protein compared with CON. Diets supplemented with 25-hydroxycholecalciferol also increased (p < 0.05) the content of superoxide dismutase (SOD), and tended to increase (p = 0.06) the total antioxidant capacity content and reduce (p = 0.09) the malondialdehyde (MDA) level in colostrum. An increase (p < 0.05) in the content of SOD and a reduction (p < 0.05) in the content of MDA in the serum of newborn piglets was also observed in the 25-hydroxycholecalciferol treatment compared with CON. Dietary 25-hydroxycholecalciferol supplementation also enhanced (p < 0.05) the immunoglobulin G content and reduced (p < 0.05) the concentration of tumor nuclear factor-α in the serum of sows, as well as reducing (p < 0.05) the content of immunoglobulin G and immunoglobulin A in the serum of newborn piglets compared with CON. Supplementation of 25-hydroxycholecalciferol in sow diets increased (p < 0.05) the content of alkaline phosphatase in the serum and colostrum of sows, the concentration of insulin and crosslap in serum of sows, and the serum calcium content of newborn piglets compared with CON. In conclusion, dietary 25-hydroxycholecalciferol supplementation from day 85 of gestation could enhance performance, antioxidant capacity, and immunoglobulin in sows and newborn piglets. [ABSTRACT FROM AUTHOR]

An 8‐year‐old boy developed serpiginous erythema on the soles of his feet and was diagnosed with cutaneous larva migrans (CLM). Following treatment with ivermectin, the erythema improved within 7 days, but it recurred 14 days later, requiring a second dose for complete resolution. Ultrasound and MRI did not reveal any parasites, but fluctuations in eosinophils, IgE and IgA levels were observed during treatment. This case highlights the importance of combining multiple diagnostic methods to evaluate treatment effectiveness. [ABSTRACT FROM AUTHOR]

This research utilized Fourier transform infrared (FTIR) spectroscopy to analyze and discuss the molecular structure of pig diets, aiming to provide new insights into the application of fermented feeds in livestock and poultry production. Moreover, the impacts of the fermented diet on growth performance, apparent digestibility, blood biochemical indices, and fecal microorganisms at different stages of pig fattening were also explored. Forty-eight pigs (Duroc × Landrace × Large white three-way hybrid) with a mean body weight of 16.55 ± 3.88 kg were randomly divided into three groups with four replicates per group and four pigs per replicate. The control group was fed a basal diet. The pigs in the fermented diet group (T1) were fed Pediococcus acidilactici (PA), Lactobacillus reuteri (LR), and Bacillus velezensis (BS) (ratio of 1:1:1) at a 6% inoculation dose. The pigs in the cooperative fermentation group (T2) were fed 6% PA, LR, BS, and a 0.2% compound enzyme preparation. The T1 and T2 diets were fermented with 45% water at 33 °C for 48 h. The pre-feeding period lasted 7 days, and the experimental period lasted 84 days. The experimental results showed that the bacterial enzyme cooperation fermentation process significantly increased the contents of crude protein, calcium, and phosphorus in the diet; increased the area of amide Ⅰ region; increased the apparent digestibility of neutral detergent fiber and phosphorus; significantly increased average daily gain; and decreased the feed-to-gain ratio in the late fattening and growth period. During the whole experiment, the serum concentrations of total protein and immunoglobulin A were significantly increased, the serum concentrations of superoxide dismutase and glucose were decreased, and the diversity and richness of fecal microorganisms were increased. These results show that the bacterial enzyme cooperative fermentation diet can improve the apparent digestibility of nutrients and improve overall health by increasing the area of amide Ⅰ region. [ABSTRACT FROM AUTHOR]

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Introduction: Topical dapsone has a level A recommendation for the treatment of papulopustular rosacea; however, its treatment efficacy has not been studied previously. The aim of this study is to evaluate the safety and efficacy of topical 7.5% dapsone gel applied once daily at night in the treatment of papulopustular rosacea. Patients and methods: This is a prospective study including female papulopustular rosacea patients with a minimum IGA score of 2. The patients were recruited at two different outpatient clinics by two independent dermatologists. The patients were prescribed 7.5% dapsone gel (same brand) for once-daily use at night. No other topical or systemic treatment modalities were allowed to be used during the study except for a sun protection factor 50 sunscreen and an emollient face cream. The patients were evaluated with the total lesion counts and IGA scores at weeks 0, 4 and 8 by two independent dermatologists. The side effects of burning, stinging, pain, erythema, and exfoliation were questioned during the follow-up visits. Results: All 32 recruited patients (18–70) completed the study. The mean lesion counts of the patients were 22.10 ± 8.95 on the initial visit, 11.90 ± 6.49 on the 4th week follow-up and 3.87 ± 3.76 on the 8th week follow up. The mean IGA scores of the patients were 3.06 ± 0.81 on the initial visit, 2.10 ± 0.87 on week 4 and 0.74 ± 0.73 on week 8. The decrease in the mean lesion count and IGA score of the patients in weeks 4 and 8 were statistically significant (p = 0.000 for all). This decrease was independent of the patient's age (p > 0.005). No side effects were reported. Conclusions: The 7.5% topical formulation of dapsone is effective for papulopustular rosacea both on the first and second months of the treatment regardless of the age of the patient. Its safe side effect profile suits for a comfortable use in rosacea patients with a decreased skin tolerance. [ABSTRACT FROM AUTHOR]

Organic fermented milk products are an area of interest combining functional properties and sustainable practices. Limited information is available regarding the specific components of organic milk that may impact the growth of lactic acid bacteria. This study emphasised the differences in bioactive compounds between organic and conventional milk and their potential influence on lactic acid bacteria growth. Analysis of organic (n = 15) and conventional (n = 15) farm milk using GC-MS revealed differences in fatty acid (FA) concentrations, mainly mono-, polyunsaturated fatty acids, and conjugated linoleic acid. Individual FA, such as stearic, linoleic, and oleic acids, were up to 33.6%, 31.0%, and 25.23% higher in conventional milk. Detection of the whey proteins using the enzyme-linked immunosorbent assay (ELISA) showed lysozyme content was up to 40.6% higher in conventional (22.04 µg L−1) than in organic (15.68 µg L−1) milk. Conversely, lactoferrin content was 20.4% higher in the organic (45.27 µg L−1) than in conventional (36.04 µg L−1). No difference in the content of immunoglobulin A was found. The higher concentrations of lysozyme, mono- and polyunsaturated fatty acids in conventional milk could enhance a higher inhibitory activity against lactic acid bacteria compared to organic milk. [ABSTRACT FROM AUTHOR]

Medium- and high-entropy alloys (M/HEAs) mix several principal elements with near-equiatomic composition and represent a model-shift strategy for designing previously unknown materials in metallurgy1-8, catalysis9-14 and other fields15-18. One of the core hypotheses of M/HEAs is lattice distortion5,19,20, which has been investigated by different numerical and experimental techniques21-26. However, determining the three-dimensional (3D) lattice distortion in M/HEAs remains a challenge. Moreover, the presumed random elemental mixing in M/HEAs has been questioned by X-ray and neutron studies27, atomistic simulations28-30, energy dispersive spectroscopy31,32 and electron diffraction33,34, which suggest the existence of local chemical order in M/HEAs. However, direct experimental observation of the 3D local chemical order has been difficult because energy dispersive spectroscopy integrates the composition of atomic columns along the zone axes7,32,34 and diffuse electron reflections may originate from planar defects instead of local chemical order35. Here we determine the 3D atomic positions of M/HEA nanoparticles using atomic electron tomography36 and quantitatively characterize the local lattice distortion, strain tensor, twin boundaries, dislocation cores and chemical short-range order (CSRO). We find that the high-entropy alloys have larger local lattice distortion and more heterogeneous strain than the medium-entropy alloys and that strain is correlated to CSRO. We also observe CSRO-mediated twinning in the medium-entropy alloys, that is, twinning occurs in energetically unfavoured CSRO regions but not in energetically favoured CSRO ones, which represents, to our knowledge, the first experimental observation of correlating local chemical order with structural defects in any material. We expect that this work will not only expand our fundamental understanding of this important class of materials but also provide the foundation for tailoring M/HEA properties through engineering lattice distortion and local chemical order.

• Associations of exposure to multiple metals with immunoglobulin levels were examined for pregnancy. • We used quantile-based g-computation, and Bayesian kernel machine regression to explore the effect of metal mixtures on Igs. • Blood Mn level was positively linked to immunoglobulin A, immunoglobulin G, and immunoglobulin M level. • Blood As level was negatively associated with immunoglobulin E levels. Metal may affect maternal immune function, but few epidemiological studies have reported the associations between multiple-metal exposure and maternal immunoglobulin (Ig) levels. Based on the Hangzhou Birth Cohort Study, 1059 participants were included, and eleven metals in whole blood samples and serum IgA, IgG, IgE and IgM levels were measured. Linear regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression (BKMR) models were used to evaluate the associations. Compared with the first tertile of metal levels, arsenic (As) was negatively associated with IgE (β = -0.25, 95% confidence interval (CI) = -0.48 to -0.02). Moreover, significant associations of manganese (Mn) with IgA, IgG and IgM were demonstrated (β = 0.10, 95% CI = 0.04 to 0.18; β = 0.07, 95% CI = 0.03 to 0.12; β = 0.10, 95% CI = 0.03 to 0.18, respectively). Cadmium (Cd) were associated with higher levels of IgM. QGC models showed the positive association of the metal mixtures with IgA and IgG, with Mn playing a major role. Mn and Cd had positive contributions to IgM, while As had negative contributions to IgE. In the BKMR models, the latent continuous outcomes of IgA and IgG showed a significant increase when all the metals were at their 60th percentile or above compared to those at their 50th percentile. Therefore, exposure to metals was associated with maternal Igs, and mainly showed that Mn was associated with increased levels of IgA, IgG and IgM, and As was associated with low IgE levels. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: The monitoring and management of blood glucose levels are of significant importance in individuals diagnosed with diabetes mellitus. Accordingly, the objective of this study was to examine the potential of a non-invasive approach for the diagnosis and management of diabetes, through the measurement of glucose concentration and salivary IgA, and a comparison with fasting glucose and serum IgA levels in individuals with type 1 and 2 diabetes, in relation to a control group of healthy individuals. Methods: This case-control study was conducted on 76 individuals with diabetes (31 with type 1 diabetes and 45 with type 2 diabetes) and 24 healthy individuals. After obtaining the code of ethics and informed consent, serum and salivary IgA levels as well as fasting glucose, were measured for each participant. The data were analyzed using SPSS version 16 statistical software and the Spearman, Kruskal-Wallis, and Mann-Whitney tests. Results: The results showed a significant difference among the three groups (type 1 diabetes, type 2 diabetes, and healthy group) based on Fasting Blood Glucose, Hemoglobin A1c, Immunoglobulin A, salivary sugar, and salivary IgA (p

AbstractObjectiveMethodsResultsConclusionTo evaluate efficacy and safety of lebrikizumab combined with topical corticosteroids (TCS) in Japanese patients with moderate-to-severe atopic dermatitis (AD).Phase 3, randomized, double-blind, placebo-controlled study (ADhere-J; NCT04760314) conducted at 37 centers in Japan (March 2021–February 2023), comprising 16-week induction (reported herein) and 52-week maintenance periods. Overall, 286 patients aged ≥12 years and ≥40 kg were randomized (interactive web response system) to subcutaneous placebo, lebrikizumab 250 mg every 4 weeks (Q4W), or lebrikizumab 250 mg every 2 weeks (Q2W) with TCS (82, 81, and 123 patients, respectively). Coprimary endpoints were proportions of patients achieving (1) Investigator’s Global Assessment score of 0 or 1 (IGA [0,1]) with ≥2-point improvement from baseline, and (2) ≥75% improvement from baseline in Eczema Area and Severity Index (EASI 75) at week 16.At week 16, compared with placebo, a significantly greater proportion of the lebrikizumab Q4W and Q2W groups achieved IGA (0,1) (6.1% vs. 29.1% and 33.4%, respectively; both p < 0.001) and EASI 75 (13.4% vs. 47.2% and 51.2%, respectively; both p < 0.001). Serious adverse events (AEs) occurred in 2.4%, 0%, and 0.8% of placebo, lebrikizumab Q4W and Q2W groups, respectively. Common treatment-emergent AEs, including pyrexia (placebo: 15.9%; lebrikizumab Q4W/Q2W: 18.5%/20.3%), conjunctivitis allergic (placebo: 4.9%; lebrikizumab Q4W/Q2W: 12.3%/17.1%), and conjunctivitis (placebo: 2.4%; lebrikizumab Q4W/Q2W: 6.2%/9.8%), were more frequent with lebrikizumab; most were mild or moderate.Consistent with global data, lebrikizumab demonstrated clinical improvements with a positive benefit-risk profile in Japanese adults and adolescents with moderate-to-severe AD through 16 weeks. [ABSTRACT FROM AUTHOR]

Epstein–Barr virus (EBV) is detected in nearly 100% of nonkeratinizing nasopharyngeal carcinoma (NPC) and EBV‐based biomarkers are used for NPC screening in endemic regions. Immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA), and recently identified anti‐BNLF2b antibodies have been shown to be the most effective screening tool; however, the screening efficacy still needs to be improved. This study developed a multiplex serological assay by testing IgA and immunoglobulin G (IgG) antibodies against representative EBV antigens that are highly transcribed in NPC and/or function crucially in viral reactivation, including BALFs, BNLF2a/b, LF1, LF2, and Zta (BZLF1). Among them, BNLF2b‐IgG had the best performance distinguishing NPC patients from controls (area under the curve: 0.951, 95% confidence interval [CI]: 0.913–0.990). Antibodies to lytic antigens BALF2 and VCA were significantly higher in advanced‐stage than in early‐stage tumors; in contrast, antibodies to latent protein EBNA1 and early lytic antigen BNLF2b were not correlated with tumor progression. Accordingly, a novel strategy combining EBNA1‐IgA and BNLF2b‐IgG was proposed and validated improving the integrated discrimination by 15.8% (95% CI: 9.8%–21.7%, p <.0001) compared with the two‐antibody method. Furthermore, we found EBV antibody profile in patients was more complicated compared with that in healthy carriers, in which stronger correlations between antibodies against different phases of antigens were observed. Overall, our serological assay indicated that aberrant latent infection of EBV in nasopharyngeal epithelial cells was probably a key step in NPC initiation, while more lytic protein expression might be involved in NPC progression. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions. Tozorakimab is a high‐affinity human monoclonal antibody that neutralizes interleukin‐33, a broad‐acting alarmin cytokine that is over‐expressed in keratinocytes of patients with AD.This Phase 2a study (FRONTIER‐2; NCT04212169) evaluated the safety and efficacy of tozorakimab in adults with moderate‐to‐severe AD.FRONTIER‐2 was a randomized, placebo‐controlled, parallel‐group, double‐blind study conducted from 9 December 2019 to 20 September 2022 at 32 centres across six countries. Patients were randomized 3:1:1:3 to receive placebo, tozorakimab 60 mg, tozorakimab 300 mg or tozorakimab 600 mg by subcutaneous injection once every 4 weeks for four doses. The primary endpoint was percentage change from baseline to Week 16 in the Eczema Area and Severity Index (EASI) score in patients treated with tozorakimab versus placebo. Secondary outcomes included EASI‐75 responders (patients achieving ≥75% reduction from baseline in EASI score), Investigator's Global Assessment (IGA) responders (patients achieving an IGA score of 0 or 1), pharmacokinetics, immunogenicity and safety.Overall, 148 patients were randomized. There was no statistically significant difference in the primary endpoint (60 mg difference of 1.3 [90% confidence interval (CI): −13.7, 16.2], p = 0.888; 300 mg: difference of 5.9 [90% CI: −10.4, 22.1], p = 0.549; 600 mg: difference of − 1.7 [90% CI: −13.4, 10.0], p = 0.807). The proportion of EASI‐75 and IGA 0/1 responders at Week 16 was numerically higher in the tozorakimab 600 mg group than in the placebo group (EASI‐75: 18.2% vs. 7.1%, p = 0.094; IGA 0/1: 9.1% vs. 1.8%, p = 0.113). Serum pharmacokinetics were dose‐dependent, immunogenicity incidence was low and tozorakimab was well tolerated.FRONTIER‐2 did not show a statistically significant difference in the primary endpoint for tozorakimab compared with placebo. However, numerical increases in responder rates were observed. [ABSTRACT FROM AUTHOR]

Enteropathies are prevalent in dog internal medicine, and their diagnosis involves a lengthy process. One of the tests requested is for biomarkers, which are important as they can provide data on intestinal functionality, intensity of inflammation, and response to treatment, and can help determine the prognosis. This study aimed to conduct a literature review on the main serum and fecal intestinal biomarkers in dogs and proposed to refine the correlations between these indicators and enteropathies. It was observed that the main biomarkers used in the intestinal evaluation of dogs were alpha 1‐proteinase inhibitory factor, immunoglobulin A, methylmalonic acid, serum folate, serum cobalamin, C‐reactive protein, fecal and serum calprotectin, and dysbiosis index. However, we suggest that more research be carried out to clarify the relationship between enteropathies and intestinal biomarkers. We noticed a lack of studies on specific intestinal markers and indicator variables in healthy dogs and those with various enteropathies; moreover, no data are available on the association of these laboratory parameters. [ABSTRACT FROM AUTHOR]

Thromboembolic complications are common in severe COVID-19 and are thought to result from excessive neutrophil-extracellular-trap (NET)-driven immunothrombosis. Glycosylation plays a vital role in the efficiency of immunoglobulin A (IgA) effector functions, with significant implications for NET formation in infectious diseases. This study represents the first comprehensive analysis of plasma IgA glycosylation during severe SARS-CoV-2 or Influenza A infection, revealing lower sialylation and higher galactosylation of IgA1 O-glycans in acute respiratory distress syndrome (ARDS), regardless of the underlying cause of the disease. Importantly, N-glycans displayed an infection-specific pattern, with N47 of IgA2 showing diminished sialylation and bisection, and N340/N327 of IgA1/2 demonstrating lower fucosylation and antennarity along with higher non-complex glycans in COVID-19 compared to Influenza. Notably, COVID-19 IgA possessed strong ability to induce NET formation and its glycosylation patterns correlated with extracellular DNA levels in plasma of critically ill COVID-19 patients. Our data underscores the necessity of further research on the role of IgA glycosylation in the modulation of pathogen-specific immune responses in COVID-19 and other infectious diseases. [ABSTRACT FROM AUTHOR]

Old World Orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) characterized by increased vascular permeability and acute kidney injury (AKI). Despite the systemic nature of the disease, the virus enters humans through inhalation and therefore initially encounters the immunoglobulin class A (IgA) dominated mucosal immune system. Herein, we characterized systemic IgA responses and their potential relationship to the mucosal immune activation by examining blood samples obtained from patients hospitalized due to acute Puumala orthohantavirus infection. Our findings reveal increased frequencies of putative IgA-expressing circulating mucosal-associated B1 cells and plasmablasts, as well as elevated levels of polyreactive, polymeric, virus-specific and secretory IgA in the acute stage of the disease. Importantly, the levels of circulating virus-specific and secretory IgA, as well as the putative IgA+ B1 cells, increased with the severity of AKI. Furthermore, circulating polymeric IgA displayed enhanced effector functions by forming stable complexes with the IgA receptor CD89 and induced pro-inflammatory neutrophil responses. These results suggest that excessive levels of circulating mucosal-like IgA might serve as a biomarker for HFRS disease progression. [ABSTRACT FROM AUTHOR]

The article in Circulation discusses a case of a 59-year-old woman with a history of bicuspid aortic valve replacement who presented with nonspecific symptoms, negative blood cultures, and elevated inflammatory markers. The patient was diagnosed with Bartonella henselae bioprosthetic aortic valve endocarditis, associated glomerulonephritis, and leukocytoclastic vasculitis. The diagnosis was challenging due to the overlap with systemic inflammatory conditions and the difficulty in traditional infectious testing. The case highlights the importance of multidisciplinary teams in solving complex diagnostic cases and the need for updated criteria for Bartonella endocarditis. [Extracted from the article]

Immunoglobulin A (IgA) is the most abundantly produced antibody in humans. IgA is a unique class of immunoglobulin due to its multiple molecular forms, and a defining difference between the two subclasses: IgA1 has a long hinge‐region that is heavily O‐glycosylated, whereas the IgA2 hinge‐region is shorter but resistant to bacterial proteases prevalent at mucosal sites. IgA is essential for immune homeostasis and education. Mucosal IgA plays a crucial role in maintaining the integrity of the mucosal barrier by immune exclusion of pathobionts while facilitating colonization with certain commensals; a large part of the gut microbiota is coated with IgA. In the circulation, monomeric IgA that has not been engaged by antigen plays a discrete role in dampening inflammatory responses. Protective and harmful roles of IgA have been studied over several decades, but a new understanding of the complex role of this immunoglobulin in health and disease has been provided by recent studies. Here, we discuss the physiological and pathological roles of IgA with a special focus on the gut, kidneys, and autoimmunity. We also discuss new IgA‐based therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments. Objectives To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids. Methods PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤ 2 at week 16. Results Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP {37.5% [95% credibility interval (Crl) 20.3–57.2] vs. 23.1% (95% Crl 6.5–49.2)} and LPP cohorts [37.5% (95% Crl 20.2–57.3) vs. 30.8% (95% Crl 10.8–57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals. Conclusions PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements. [ABSTRACT FROM AUTHOR]

Background: Hyperkeratotic hand and foot dermatitis significantly affects quality of life. Some patients respond suboptimally to topical corticosteroids and have multiple recurrences. Objective: Our aim was to compare the efficacy and safety profile of apremilast and topical corticosteroid versus corticosteroid alone in hyperkeratotic hand and foot dermatitis. Methods: This randomized controlled study involved 77 patients treated for 3 months. Group A (39 patients) received mometasone furoate 0.1% cream with oral apremilast 30 mg twice daily, and Group B (38 patients) received mometasone alone. They were assessed monthly using the Hand Eczema Clinical Severity Index (HECSI) and Visual Analogue Scale (VAS) scores for pruritus. Investigator Global Assessment (IGA) and Quality of Life in Hand Eczema Questionnaire (QOLHEQ) were conducted at the end of 3 months. Results: The HECSI, VAS score, and QOLHEQ showed a significant decrease in both groups from baseline to the third month. Intergroup comparisons of HECSI failed to reach the significance level. When compared, patients receiving apremilast had significantly better improvement in the third month according to the Patient Global Assessment (PGA) and Investigator Global Assessment (IGA). They also had a smaller number of flares. Conclusion: Adding apremilast to topical corticosteroid leads to better patient and physician‐perceived improvement and reduces the number of flares in hyperkeratotic hand eczema. [ABSTRACT FROM AUTHOR]

Background/Aim: Pasteurella multocida is a significant cause of morbidity and mortality in rabbits, as well as other species. Some isolates elaborate a heat-labile toxin (PMT) that has been shown to be an important virulence factor. Though previous studies have demonstrated protective immunity can be conferred via immunization of rabbits with heat-inactivated PMT (IPMT), we investigated the ability of immunization to impact colonization of P. multocida. Materials and Methods: Rabbits were immunized at days 0, 7 and 14 with either phosphate buffered saline (PBS), the mucosal adjuvant cholera toxin (CT), IMPT or IPMT + CT. Male New Zealand white rabbits were used and confirmed to be free of P. multocida prior to experimentation. Results: Serum IgG and nasal lavage fluid IgA responses directed against PMT were found in rabbits immunized with IPMT, with or without CT, but not in those immunized with only PBS or CT; and the addition of CT to IPMT enhanced the response. Significantly more P. multocida CFUs (p≤0.05) were cultured from the lungs of rabbits immunized with IPMT, with or without CT, compared to those administered only PBS or CT, although no differences were observed in nasal lavage fluid samples. Further, immunization IPMT, with or without CT, conferred protection against pleuritis and pneumonia. Conclusion: PMT, in addition to its role as a virulence factor, may serve as a colonization factor for P. multocida in the lungs of rabbits. [ABSTRACT FROM AUTHOR]