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1.
Nat Commun ; 15(1): 5589, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961063

ABSTRACT

As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent SARS-CoV-2 vaccine candidates (TVC) based on three components of the MMR vaccine: measles virus (MeV), mumps virus (MuV) Jeryl Lynn (JL1) strain, and MuV JL2 strain. Specifically, MeV, MuV-JL1, and MuV-JL2 vaccine strains, each expressing prefusion spike (preS-6P) from a different variant of concern (VoC), were combined to generate TVCs. Intranasal immunization of IFNAR1-/- mice and female hamsters with TVCs generated high levels of S-specific serum IgG antibodies, broad neutralizing antibodies, and mucosal IgA antibodies as well as tissue-resident memory T cells in the lungs. The immunized female hamsters were protected from challenge with SARS-CoV-2 original WA1, B.1.617.2, and B.1.1.529 strains. The preexisting MeV and MuV immunity does not significantly interfere with the efficacy of TVC. Thus, the trivalent platform is a promising next-generation SARS-CoV-2 vaccine candidate.


Subject(s)
Administration, Intranasal , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Animals , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Female , SARS-CoV-2/immunology , SARS-CoV-2/genetics , COVID-19/prevention & control , COVID-19/immunology , COVID-19/virology , Antibodies, Viral/immunology , Antibodies, Viral/blood , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Mice , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Cricetinae , Humans , Measles-Mumps-Rubella Vaccine/immunology , Measles-Mumps-Rubella Vaccine/administration & dosage , Measles virus/immunology , Measles virus/genetics , Immunoglobulin G/blood , Immunoglobulin G/immunology , Mumps virus/immunology , Mumps virus/genetics , Mice, Knockout , Mesocricetus , Immunoglobulin A/immunology , Immunoglobulin A/blood
2.
Sci Transl Med ; 16(754): eadl3848, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38959329

ABSTRACT

Autoantibodies to nuclear antigens are hallmarks of systemic lupus erythematosus (SLE) where they contribute to pathogenesis. However, there remains a gap in our knowledge regarding how different isotypes of autoantibodies contribute to this autoimmune disease, including the production of the critical type I interferon (IFN) cytokines by plasmacytoid dendritic cells (pDCs) in response to immune complexes (ICs). We focused on IgA, which is the second-most prevalent isotype in serum and, along with IgG, is deposited in glomeruli in individuals with lupus nephritis. We show that individuals with SLE have serum IgA autoantibodies against most nuclear antigens, correlating with IgG against the same antigen. We investigated whether IgA autoantibodies against a major SLE autoantigen, Smith ribonucleoprotein (Sm/RNP), played a role in IC activation of pDCs. We found that pDCs expressed the IgA-specific Fc receptor, FcαR, and IgA1 autoantibodies synergized with IgG in RNA-containing ICs to generate robust primary blood pDC IFN-α responses in vitro. pDC responses to these ICs required both FcαR and FcγRIIa, showing synergy between these Fc receptors. Sm/RNP IC binding to and internalization by pDCs were greater when ICs contained both IgA1 and IgG. Circulating pDCs from individuals with SLE had higher binding of IgA1-containing ICs and higher expression of FcαR than pDCs from healthy control individuals. Although pDC FcαR expression correlated with the blood IFN-stimulated gene signature in SLE, Toll-like receptor 7 agonists, but not IFN-α, up-regulated pDC FcαR expression in vitro. Together, we show a mechanism by which IgA1 autoantibodies contribute to SLE pathogenesis.


Subject(s)
Antigen-Antibody Complex , Autoantibodies , Dendritic Cells , Immunoglobulin A , Immunoglobulin G , Lupus Erythematosus, Systemic , Humans , Dendritic Cells/immunology , Dendritic Cells/metabolism , Immunoglobulin A/immunology , Immunoglobulin A/metabolism , Immunoglobulin A/blood , Autoantibodies/immunology , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Antigen-Antibody Complex/immunology , Antigen-Antibody Complex/metabolism , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/blood , RNA/metabolism , Female , Interferon-alpha/metabolism , Adult , Receptors, Fc/metabolism , Receptors, Fc/immunology , Toll-Like Receptor 7/metabolism , Male , Receptors, IgG/metabolism
3.
Front Immunol ; 15: 1406794, 2024.
Article in English | MEDLINE | ID: mdl-38953030

ABSTRACT

Introduction: Equine asthma (EA) is a common lower airway disease in horses, but whether its pathogenesis is allergic is ambiguous. Extrinsic stimuli like hay dust induce acute exacerbation of clinical signs and sustained local neutrophilic inflammation in susceptible horses. Aspergillus fumigatus is an EA stimulus, but it is unclear if it merely acts as an IgE-provoking allergen. We aimed to comprehensively analyze immunoglobulin (Ig) isotypes in EA, elucidating their binding to different A. fumigatus antigens, and their quantities systemically in serum and locally in bronchoalveolar lavage fluid (BALF). Methods: Serum and BALF from healthy horses (HE, n = 18) and horses with mild-moderate asthma (MEA, n = 20) or severe asthma (SEA, n = 24) were compared. Ig isotype (IgG1, IgG3/5, IgG4/7, IgG6, IgA, and IgE) binding to nine antigens (A. fumigatus lysate, and recombinant Asp f 1, Asp f 7, Asp f 8, dipeptidyl-peptidase 5, class II aldolase/adducin domain protein, glucoamylase, beta-hexosaminidase, and peptide hydrolase) was compared by enzyme-linked immunosorbent assays. Total Ig isotype contents were determined by bead-based assays. Results: MEA and SEA differed from HE but hardly from each other. Compared to HE, asthmatic horses showed increased anti-A. fumigatus binding of IgG (BALF and serum) and IgA (BALF). Serum and BALF IgE binding and total IgE contents were similar between HE and EA. Single antigens, as well as A. fumigatus lysate, yielded similar Ig binding patterns. Serum and BALF IgG1 binding to all antigens was increased in SEA and to several antigens in MEA. Serum IgG4/7 binding to two antigens was increased in SEA. BALF IgA binding to all antigens was increased in SEA and MEA. Total BALF IgG1 and IgG4/7 contents were increased in SEA, and serum IgG4/7 content was increased in MEA compared to HE. Yet, total isotype contents differentiated EA and HE less clearly than antigen-binding Ig. Discussion: A. fumigatus immunogenicity was confirmed without identification of single dominant antigens here. A. fumigatus provoked elevated BALF IgG1 and IgA binding, and these isotypes appear relevant for neutrophilic EA, which does not support allergy. BALF Ig isotype differentiation beyond IgE is crucial for a comprehensive analysis of immune responses to fungi in EA pathogenesis.


Subject(s)
Antigens, Fungal , Aspergillus fumigatus , Asthma , Bronchoalveolar Lavage Fluid , Horse Diseases , Immunoglobulin A , Immunoglobulin G , Animals , Horses/immunology , Aspergillus fumigatus/immunology , Bronchoalveolar Lavage Fluid/immunology , Asthma/immunology , Asthma/microbiology , Immunoglobulin G/immunology , Immunoglobulin G/blood , Immunoglobulin A/immunology , Immunoglobulin A/blood , Immunoglobulin A/metabolism , Horse Diseases/immunology , Horse Diseases/microbiology , Antigens, Fungal/immunology , Male , Neutrophils/immunology , Neutrophils/metabolism , Female , Immunoglobulin E/immunology , Immunoglobulin E/blood , Antibodies, Fungal/immunology , Antibodies, Fungal/blood
4.
Int J Epidemiol ; 53(4)2024 Jun 12.
Article in English | MEDLINE | ID: mdl-39008896

ABSTRACT

BACKGROUND: Epstein-Barr virus (EBV) is a major cause of nasopharyngeal carcinoma (NPC) and measurement of different EBV antibodies in blood may improve early detection of NPC. Prospective studies can help assess the roles of different EBV antibodies in predicting NPC risk over time. METHODS: A case-cohort study within the prospective China Kadoorie Biobank of 512 715 adults from 10 (including two NPC endemic) areas included 295 incident NPC cases and 745 subcohort participants. A multiplex serology assay was used to quantify IgA and IgG antibodies against 16 EBV antigens in stored baseline plasma samples. Cox regression was used to estimate adjusted hazard ratios (HRs) for NPC and C-statistics to assess the discriminatory ability of EBV-markers, including two previously identified EBV-marker combinations, for predicting NPC. RESULTS: Sero-positivity for 15 out of 16 EBV-markers was significantly associated with higher NPC risk. Both IgA and IgG antibodies against the same three EBV-markers showed the most extreme HRs, i.e. BGLF2 (IgA: 124.2 (95% CI: 63.3-243.9); IgG: 8.6 (5.5-13.5); LF2: [67.8 (30.0-153.1), 10.9 (7.2-16.4)]); and BFRF1: 26.1 (10.1-67.5), 6.1 (2.7-13.6). Use of a two-marker (i.e. LF2/BGLF2 IgG) and a four-marker (i.e. LF2/BGLF2 IgG and LF2/EA-D IgA) combinations yielded C-statistics of 0.85 and 0.84, respectively, which persisted for at least 5 years after sample collection in both endemic and non-endemic areas. CONCLUSIONS: In Chinese adults, plasma EBV markers strongly predict NPC occurrence many years before clinical diagnosis. LF2 and BGLF2 IgG could identify NPC high-risk individuals to improve NPC early detection in community and clinical settings.


Subject(s)
Antibodies, Viral , Early Detection of Cancer , Epstein-Barr Virus Infections , Herpesvirus 4, Human , Immunoglobulin A , Immunoglobulin G , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Male , China/epidemiology , Female , Middle Aged , Herpesvirus 4, Human/immunology , Prospective Studies , Antibodies, Viral/blood , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/blood , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Carcinoma/epidemiology , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/blood , Nasopharyngeal Neoplasms/immunology , Nasopharyngeal Neoplasms/epidemiology , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/epidemiology , Epstein-Barr Virus Infections/blood , Adult , Immunoglobulin A/blood , Early Detection of Cancer/methods , Immunoglobulin G/blood , Aged , Case-Control Studies , Proportional Hazards Models , East Asian People
5.
Pol J Microbiol ; 73(2): 123-130, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38905276

ABSTRACT

Serological testing can be a powerful complementary approach to achieve timely diagnosis of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, along with nucleic acid detection. Immunoglobulin (Ig) A antibodies are less frequently utilized to detect SARS-CoV-2 infection than IgM and IgG antibodies, even though IgA antibodies play an important role in protective immunity against SARS-CoV-2. This review discusses the differences in kinetics and assay performance between IgA and IgM antibodies and the factors influencing antibody responses. It highlights the potential usefulness of analyzing IgA antibodies for the early detection of SARS-CoV-2 infection. The early appearance of IgA and the high sensitivity of IgA-based immunoassays can aid in diagnosing coronavirus disease 2019. However, because of cross-reactivity, it is important to recognize the only moderate specificity of the early detection of SARS-CoV-2 IgA antibodies against spike antigens. Either the analysis of antibodies targeting the nucleocapsid antigen or a combination of antibodies against the nucleocapsid and spike antigens may strengthen the accuracy of serological evaluation.


Subject(s)
Antibodies, Viral , COVID-19 , Immunoglobulin A , Immunoglobulin M , SARS-CoV-2 , Humans , COVID-19/diagnosis , COVID-19/immunology , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , SARS-CoV-2/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Early Diagnosis , COVID-19 Serological Testing/methods , Sensitivity and Specificity
6.
Sci Rep ; 14(1): 12725, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830902

ABSTRACT

Humoral immunity in COVID-19 includes antibodies (Abs) targeting spike (S) and nucleocapsid (N) SARS-CoV-2 proteins. Antibody levels are known to correlate with disease severity, but titers are poorly reported in mild or asymptomatic cases. Here, we analyzed the titers of IgA and IgG against SARS-CoV-2 proteins in samples from 200 unvaccinated Hospital Workers (HWs) with mild COVID-19 at two time points after infection. We analyzed the relationship between Ab titers and patient characteristics, clinical features, and evolution over time. Significant differences in IgG and IgA titers against N, S1 and S2 proteins were found when samples were segregated according to time T1 after infection, seroprevalence at T1, sex and age of HWs and symptoms at infection. We found that IgM + samples had higher titers of IgG against N antigen and IgA against S1 and S2 antigens than IgM - samples. There were significant correlations between anti-S1 and S2 Abs. Interestingly, IgM + patients with dyspnea had lower titers of IgG and IgA against N, S1 and S2 than those without dyspnea. Comparing T1 and T2, we found that IgA against N, S1 and S2 but only IgG against certain Ag decreased significantly. In conclusion, an association was established between Ab titers and the development of infection symptoms.


Subject(s)
Antibodies, Viral , COVID-19 , Immunoglobulin A , Immunoglobulin G , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/virology , COVID-19/blood , Immunoglobulin A/blood , Immunoglobulin A/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , SARS-CoV-2/immunology , Female , Antibodies, Viral/immunology , Antibodies, Viral/blood , Adult , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Coronavirus Nucleocapsid Proteins/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Immunity, Humoral , Phosphoproteins/immunology
7.
J Med Virol ; 96(6): e29713, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38874194

ABSTRACT

Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence is used to estimate the proportion of individuals within a population previously infected, to track viral transmission, and to monitor naturally and vaccine-induced immune protection. However, in sub-Saharan African settings, antibodies induced by higher exposure to pathogens may increase unspecific seroreactivity to SARS-CoV-2 antigens, resulting in false positive responses. To investigate the level and type of unspecific seroreactivitiy to SARS-CoV-2 in Africa, we measured immunoglobulin G (IgG), IgA, and IgM to a broad panel of antigens from different pathogens by Luminex in 602 plasma samples from African and European subjects differing in coronavirus disease 2019, malaria, and other exposures. Seroreactivity to SARS-CoV-2 antigens was higher in prepandemic African than in European samples and positively correlated with antibodies against human coronaviruses, helminths, protozoa, and especially Plasmodium falciparum. African subjects presented higher levels of autoantibodies, a surrogate of polyreactivity, which correlated with P. falciparum and SARS-CoV-2 antibodies. Finally, we found an improved sensitivity in the IgG assay in African samples when using urea as a chaotropic agent. In conclusion, our data suggest that polyreactive antibodies induced mostly by malaria are important mediators of the unspecific anti-SARS-CoV-2 responses, and that the use of dissociating agents in immunoassays could be useful for more accurate estimates of SARS-CoV-2 seroprevalence in African settings.


Subject(s)
Antibodies, Viral , COVID-19 , Immunoglobulin G , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/epidemiology , Antibodies, Viral/blood , Seroepidemiologic Studies , SARS-CoV-2/immunology , Immunoglobulin G/blood , Adult , Male , Female , Middle Aged , Malaria/epidemiology , Malaria/immunology , Malaria/blood , Immunoglobulin M/blood , Young Adult , Aged , Adolescent , Europe/epidemiology , Immunoglobulin A/blood , Endemic Diseases , Africa/epidemiology , Africa South of the Sahara/epidemiology
8.
BMJ Case Rep ; 17(6)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38901853

ABSTRACT

A man in his 40s with end-stage kidney disease due to IgA nephropathy and receiving peritoneal dialysis presented with a 1-week history of breathlessness, cough and nosebleeds. CT scan of the chest revealed ground glass changes while blood tests indicated elevated inflammatory markers and a negative vasculitis screen. This included negative ANCA and anti-GBM antibodies. Initial treatment for suspected atypical pneumonia with antibiotics yielded no clinical improvement.Over the course of the admission, his symptoms progressively worsened, leading to oxygen dependency with a FiO2 of 40% and episodes of haemoptysis. Suspicions of pulmonary vasculitis arose due to clinical deterioration, prompting consultation with a tertiary vasculitis centre. It was subsequently concluded that the clinical and radiological findings correlated with ANCA-negative pulmonary vasculitis or a rare case of IgA-associated pulmonary capillaritis. Treatment with methylprednisolone and rituximab led to significant improvement, allowing rapid oxygen withdrawal. The patient was discharged with a tapering prednisolone regimen.


Subject(s)
Antibodies, Antineutrophil Cytoplasmic , Humans , Male , Antibodies, Antineutrophil Cytoplasmic/blood , Adult , Rituximab/therapeutic use , Vasculitis/diagnosis , Vasculitis/drug therapy , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , Diagnosis, Differential , Tomography, X-Ray Computed , Kidney Failure, Chronic/complications , Lung Diseases/diagnosis , Lung Diseases/drug therapy , Lung Diseases/diagnostic imaging , Immunoglobulin A/blood
9.
PeerJ ; 12: e17498, 2024.
Article in English | MEDLINE | ID: mdl-38827305

ABSTRACT

Background: The method currently available to diagnose shigellosis is insensitive and has many limitations. Thus, this study was designed to identify specific antigenic protein(s) among the cell surface associated proteins (SAPs) of Shigella that would be valuable in the development of an alternative diagnostic assay for shigellosis, particularly one that could be run using a stool sample rather than serum. Methods: The SAPs of clinical isolates of S. dysenteriae, S. boydii, Shigella flexneri, and S. sonnei were extracted from an overnight culture grown at 37 °C using acidified-glycine extraction methods. Protein profiles were observed by SDS-PAGE. To determine if antibodies specific to certain Shigella SAPs were present in both sera and stool suspensions, Western blot analysis was used to detect the presence of IgA, IgG, and IgM. Results: Immunoblot analysis revealed that sera from patients infected with S. flexneri recognized 31 proteins. These SAP antigens are recognized by the host humoral response during Shigella infection. Specific antibodies against these antigens were also observed in intestinal secretions of shigellosis patients. Of these 31 S. flexneri proteins, the 35 kDa protein specifically reacted against IgA present in patients' stool suspensions. Further study illustrated the immunoreactivity of this protein in S. dysenteriae, S. boydii, and S. sonnei. This is the first report that demonstrates the presence of immunoreactive Shigella SAPs in stool suspensions. The SAPSs could be very useful in developing a simple and rapid serodiagnostic assay for shigellosis directly from stool specimens.


Subject(s)
Bacterial Proteins , Dysentery, Bacillary , Feces , Shigella flexneri , Humans , Feces/microbiology , Feces/chemistry , Dysentery, Bacillary/diagnosis , Dysentery, Bacillary/immunology , Dysentery, Bacillary/microbiology , Shigella flexneri/immunology , Shigella flexneri/isolation & purification , Bacterial Proteins/immunology , Bacterial Proteins/analysis , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Antigens, Bacterial/immunology , Antigens, Bacterial/analysis , Blotting, Western , Electrophoresis, Polyacrylamide Gel , Immunoglobulin A/immunology , Immunoglobulin A/blood , Immunoglobulin A/analysis
10.
Medicine (Baltimore) ; 103(23): e38416, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847724

ABSTRACT

To investigate the expression of Inhibin B between various clinical stages, Chinese medicine dialectic typing, and in nasopharyngeal carcinoma (NPC) tissues and serum, and to evaluate the potential of Inhibin B as a new biomarker for NPC. Paraffin specimens of pathologically confirmed NPC tissues and paracancerous tissues were retrospectively collected, and the expression of Inhibin α (INHA) and Inhibin ßB (INHBB) was detected by SP method, and their relationship with clinicopathological indexes was analyzed; in addition, patients with NPC who had received radiotherapy were included as the study subjects, and Epstein-Barr virus DNA (EBV-DNA), INHA, and INHBB in patients were detected by using the fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and chemiluminescent immuno-sandwiching method, respectively. EBV-DNA, EBV-viral capsid antigen-immunoglobulin A (VCA IgA), INHA, and INHBB were detected in the patients, respectively, and their relationships with traditional Chinese medicine (TCM) patterns were also analyzed. The expression of INHA and INHBB in NPC tissues was lower than that in paracancerous tissues, and the expression of INHA in NPC patients was correlated with lymphatic metastasis, clinical staging, and TCM staging; the levels of EBV-DNA and VCA IgA were higher than that of healthy populations in NPC patients and were higher than that of patients with stage III + IV than that of patients with stage I + II, and the levels of INHA and INHBB were lower than those of healthy populations and were lower than those of patients with stage III + IV than that of patients with stage I + II. The levels of INHA and INHBB in nasopharyngeal cancer patients were lower than those in healthy people, and the levels in stage III + IV patients were lower than those in stage I + II patients. The levels of EBV-DNA and VCA IgA in nasopharyngeal cancer patients were correlated with the Chinese medicine patterns, and had different patterns. The expression of Inhibin B may be related to the progression of NPC, and it has certain typing significance for different TCM syndromes of NPC, which is helpful for TCM typing diagnosis.


Subject(s)
Medicine, Chinese Traditional , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Male , Female , Nasopharyngeal Neoplasms/virology , Nasopharyngeal Neoplasms/diagnosis , Nasopharyngeal Neoplasms/blood , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Carcinoma/diagnosis , Nasopharyngeal Carcinoma/virology , Nasopharyngeal Carcinoma/blood , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/pathology , Medicine, Chinese Traditional/methods , Middle Aged , Retrospective Studies , Adult , DNA, Viral/analysis , DNA, Viral/blood , Inhibins/blood , Herpesvirus 4, Human/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/blood , Neoplasm Staging , Inhibin-beta Subunits/metabolism , Inhibin-beta Subunits/blood , Aged , Antigens, Viral/blood , Immunoglobulin A/blood , Capsid Proteins
11.
Clin Rheumatol ; 43(7): 2253-2260, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38842744

ABSTRACT

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.


Subject(s)
Autoantibodies , Celiac Disease , Myositis , Humans , Celiac Disease/epidemiology , Celiac Disease/immunology , Celiac Disease/blood , Celiac Disease/diagnosis , Celiac Disease/complications , Cross-Sectional Studies , Female , Male , Middle Aged , Adult , Prevalence , Autoantibodies/blood , Myositis/immunology , Myositis/epidemiology , Myositis/blood , Mexico/epidemiology , Transglutaminases/immunology , Aged , Immunoglobulin A/blood , Gliadin/immunology , Immunoglobulin G/blood , Protein Glutamine gamma Glutamyltransferase 2
12.
Virol J ; 21(1): 138, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872127

ABSTRACT

BACKGROUND: Infection with SARS-CoV-2 in high-risk groups such as kidney transplant and dialysis patients is shown to be associated with a more serious course of the disease. Four years after the start of the COVID-19 pandemic, crucial knowledge on the immune responses in these patient groups is still lacking. Therefore, this study aimed at investigating the humoral immune response after a SARS-CoV-2 infection compared to vaccination as well as the evolution of immunoglobulins over time. METHODS: Kidney transplant recipients, patients on haemodialysis or on peritoneal dialysis and healthy controls were included in this longitudinal multicenter study. SARS-CoV-2 anti-RBD, anti-NP and anti-S1S2 immunoglobulin G (IgG) and A (IgA) as well as the neutralizing antibody capacity were measured. RESULTS: Kidney transplant recipients had a significantly better humoral response to SARS-CoV-2 after infection (86.4%) than after a two-dose mRNA vaccination (55.8%) while seroconversion was comparable in patients on haemodialysis after infection (95.8%) versus vaccination (89.4%). In individuals without prior COVID-19, the IgG levels after vaccination were significantly lower in kidney transplant recipients when compared to all other groups. However, the IgA titres remained the highest in this patient group at each time point, both after infection and vaccination. A history COVID-19 was associated with higher antibody levels after double-dose vaccination in all patient categories and, while decreasing, titres remained high six months after double-dose vaccination. CONCLUSION: Kidney transplant recipients had a more robust humoral response to SARS-CoV-2 following infection compared to a two-dose mRNA vaccination, while patients on haemodialysis exhibited comparable seroconversion rates. Notably, individuals with prior COVID-19 exhibited higher IgG levels in response to vaccination. Hybrid immunity is thus the best possible defence against severe COVID-19 disease and seems also to hold up for these populations. Next, it is not clear whether the higher IgA levels in the kidney transplant recipients is beneficial for neutralizing SARS-CoV-2 or if it is a sign of disease severity.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunity, Humoral , Immunoglobulin A , Immunoglobulin G , Kidney Transplantation , Renal Dialysis , SARS-CoV-2 , Transplant Recipients , Vaccination , Humans , Kidney Transplantation/adverse effects , COVID-19/immunology , COVID-19/prevention & control , Immunoglobulin G/blood , Male , Female , Immunoglobulin A/blood , Middle Aged , Antibodies, Viral/blood , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Aged , Adult , Longitudinal Studies , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Spike Glycoprotein, Coronavirus/immunology
13.
Arch Pediatr ; 31(5): 293-298, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38811264

ABSTRACT

BACKGROUND: The pneumococcal antibody response after vaccination with unconjugated pneumococcal vaccine can be evaluated as part of the diagnostic work-up of children with recurrent respiratory tract infections to detect an underlying polysaccharide antibody deficiency. Little is known about the prevalence of polysaccharide antibody deficiency in this population and its therapeutic consequences. OBJECTIVES: This study aimed to investigate the prevalence of polysaccharide antibody deficiency in children with recurrent respiratory tract infections and to correlate polysaccharide responsiveness with clinical severity. In addition, we aimed to evaluate differences in the immunoglobulin (Ig)G2/IgG ratio, IgA level, and age in relation to the number of deficient serotype-specific antibody responses. METHODS: Polysaccharide antibody titers for pneumococcal serotypes 8, 9N, and 15B; clinical characteristics; and immunoglobulin levels of 103 children with recurrent respiratory tract infections were retrospectively assessed. American Academy of Allergy, Asthma, and Immunology guidelines were used for the interpretation of the polysaccharide antibody response. RESULTS: Overall, 28 children (27.2 %) were diagnosed with polysaccharide antibody deficiency. No correlation was found between the number of deficient serotype-specific antibody responses and clinical severity. The study participants with a normal response to all three serotypes had a higher IgG2/IgG ratio than those with one or more deficient responses (p < 0.003). No significant correlation between IgA levels and polysaccharide responsiveness was found. The median age of children with normal polysaccharide responsiveness for the three tested serotypes was higher than that of children with a deficient response to one or more serotypes (p < 0.0025). CONCLUSION: For a large group of children (18.4 %) with recurrent respiratory tract infections, an underlying mechanism for their susceptibility was defined thanks to diagnostic unconjugated pneumococcal polysaccharide vaccination. Further research is needed to formulate age-specific normal values for polysaccharide responsiveness and to investigate the usefulness of the IgG2/IgG ratio in determining the need for diagnostic unconjugated pneumococcal polysaccharide vaccination.


Subject(s)
Antibodies, Bacterial , Immunoglobulin G , Pneumococcal Vaccines , Recurrence , Respiratory Tract Infections , Streptococcus pneumoniae , Humans , Female , Male , Respiratory Tract Infections/immunology , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Child, Preschool , Child , Antibodies, Bacterial/blood , Pneumococcal Vaccines/immunology , Pneumococcal Vaccines/administration & dosage , Retrospective Studies , Streptococcus pneumoniae/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Infant , Pneumococcal Infections/immunology , Pneumococcal Infections/prevention & control , Pneumococcal Infections/diagnosis , Pneumococcal Infections/epidemiology , Adolescent , Immunoglobulin A/blood , Antibody Formation/immunology
14.
J Pediatr Gastroenterol Nutr ; 79(1): 84-91, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38769762

ABSTRACT

OBJECTIVES: European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines enable the diagnosis of celiac disease (CD) without biopsies in patients with immunoglobulin A (IgA)-antibodies against tissue transglutaminase (TGA-IgA) ≥ 10× the upper limit of normal (ULN) and positivity of endomysial antibodies in a second blood sample. Limited data exist comparing the biopsy versus the nonbiopsy diagnostic approach regarding long-term outcomes in CD patients. Our study aimed to investigate the influence of the diagnostic approach on adherence to gluten-free diet (GFD), serological remission (defined as normalization of TGA-IgA during follow-up (FU)) and clinical remission in CD patients with TGA-IgA ≥ 10× ULN. METHODS: Retrospective multicenter study. Patients with CD and TGA-IgA ≥ 10× ULN at diagnosis were included in the study. Patients with confirmed diagnosis by biopsy were compared to patients diagnosed by nonbiopsy approach using univariate analysis, Kaplan-Meier survival curve, and logistic regression models. RESULTS: A total of 282 CD patients (192 [68.1%] in the biopsy group; 90 [31.9%] in the nonbiopsy group) were analyzed. The median time to normalization of TGA-IgA was 16.5 months [interquartile range, IQR: 13, 28] in the biopsy and 15 months [IQR: 12, 26] in the nonbiopsy group; p = 0.14). Rates of normalized TGA-IgA at first to third-year FU were comparable between both groups. Adherence to GFD did not seem to be influenced by the diagnostic approach. CONCLUSIONS: The nonbiopsy approach is not inferior to the biopsy approach in terms of adherence to GFD and serological remission in patients with CD.


Subject(s)
Celiac Disease , Diet, Gluten-Free , Immunoglobulin A , Transglutaminases , Humans , Celiac Disease/diagnosis , Celiac Disease/diet therapy , Celiac Disease/blood , Celiac Disease/immunology , Retrospective Studies , Male , Child , Female , Biopsy , Transglutaminases/immunology , Child, Preschool , Adolescent , Immunoglobulin A/blood , Autoantibodies/blood , Protein Glutamine gamma Glutamyltransferase 2 , GTP-Binding Proteins/immunology , Treatment Outcome , Follow-Up Studies , Infant , Patient Compliance
15.
Ann Surg Oncol ; 31(8): 4864-4867, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38767805

ABSTRACT

OBJECTIVE: Immunotherapy-tyrosine kinase inhibitor (IO-TKI) therapy has revolutionized the treatment landscape for metastatic clear cell renal cell carcinoma (mccRCC); however, the absence of effective biomarkers poses a challenge in predicting the efficacy of these regimens. This study aims to explore the predictive and prognostic value of serum immunoglobulin A (IgA) in mccRCC patients undergoing IO-TKI therapy. METHODS: Ninety-six mccRCC patients treated with IO-TKI therapy from 2019 to 2023 were enrolled and serum IgA levels were assessed at the pretreatment baseline and after 3 months of treatment. RESULTS: Notably, baseline levels of IgA showed no correlation with the objective response rate. However, patients achieving complete or partial responses exhibited a remarkable decrease in IgA levels, while those with stable or progressive disease displayed an increase in IgA levels after 3 months of treatment. Furthermore, the dynamic alteration in IgA levels after 3 months of treatment demonstrated predictive value for both progression-free survival (PFS) and overall survival (OS). The time-dependent receiver operating characteristic curves exhibited outstanding performance in predicting PFS (AUC 0.793) and OS (AUC 0.738). CONCLUSION: Taken together, this study demonstrates that dynamic alteration of serum IgA after 3 months of treatment was significantly correlated with prognosis and therapeutic efficacy in mccRCC patients.


Subject(s)
Biomarkers, Tumor , Carcinoma, Renal Cell , Immunoglobulin A , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/pathology , Male , Female , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/blood , Middle Aged , Immunoglobulin A/blood , Survival Rate , Prognosis , Aged , Biomarkers, Tumor/blood , Follow-Up Studies , Adult , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Immunotherapy/methods , Aged, 80 and over
16.
Nutrients ; 16(9)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38732587

ABSTRACT

Heat-treated Lactiplantibacillus plantarum nF1 (HT-nF1) increases immune cell activation and the production of various immunomodulators (e.g., interleukin (IL)-12) as well as immunoglobulin (Ig) G, which plays an important role in humoral immunity, and IgA, which activates mucosal immunity. To determine the effect of HT-nF1 intake on improving immune function, a randomized, double-blind, placebo-controlled study was conducted on 100 subjects with normal white blood cell counts. The HT-nF1 group was administered capsules containing 5 × 1011 cells of HT-nF1 once a day for 8 weeks. After 8 weeks of HT-nF1 intake, significant changes in IL-12 were observed in the HT-nF1 group (p = 0.045). In particular, the change in natural killer (NK) cell activity significantly increased in subjects with low secretory (s) IgA (≤49.61 µg/mL) and low NK activity (E:T = 10:1) (≤3.59%). These results suggest that HT-nF1 has no safety issues and improves the innate immune function by regulating T helper (Th)1-related immune factors. Therefore, we confirmed that HT-nF1 not only has a positive effect on regulating the body's immunity, but it is also a safe material for the human body, which confirms its potential as a functional health food ingredient.


Subject(s)
Interleukin-12 , Killer Cells, Natural , Probiotics , Adult , Female , Humans , Male , Middle Aged , Double-Blind Method , Hot Temperature , Immune System , Immunity, Innate , Immunoglobulin A/blood , Killer Cells, Natural/immunology , Lactobacillus plantarum , Probiotics/administration & dosage
17.
Metabolomics ; 20(3): 61, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38787468

ABSTRACT

INTRODUCTION: IgA vasculitis diagnosis relies primarily on clinical features and is confirmed by pathological findings. To date, there is no reliable noninvasive diagnostic biomarker. OBJECTIVE: We aimed to explore the baseline serum metabolome of adult patients with IgA vasculitis to identify potential diagnostic biomarkers. METHODS: We performed a study comparing the serum metabolome of patients with IgA vasculitis to that of patients with inflammatory condition, namely spondyloarthritis. Serum analyses were performed by high-performance liquid chromatography-mass spectrometry. RESULTS: Fifty-five patients with IgA vasculitis and 77 controls with spondyloarthritis (age- and sex-matched) were included in this study. The median age of IgA vasculitis patients was 53 years. Two-thirds of patients were female (n = 32). At the time of vasculitis diagnosis, 100% of patients had skin involvement and 69% presented with glomerulonephritis (n = 38). Joint and digestive involvement were observed in 56% (n = 31) and 42% (n = 23) of patients. Four discriminative metabolites between the two groups were identified: 1-methyladenosine, L-glutamic acid, serotonin, and thymidine. The multivariate model built from the serum metabolomes of patients with IgA vasculitis and spondyloarthritis revealed an accuracy > 90%. As this model was significant according to the permutation test (p < 0.01), independent validation showed an excellent predictive value of the test set: sensitivity 98%; specificity 98%, positive predictive value 97% and negative predictive value 98%. CONCLUSION: To our knowledge, this study is the first to use the metabolomic approach for diagnostic purposes in adult IgA vasculitis, highlighting a specific diagnostic metabolome signature.


Subject(s)
Biomarkers , Immunoglobulin A , Metabolome , Humans , Female , Male , Middle Aged , Adult , Biomarkers/blood , Immunoglobulin A/blood , Chromatography, High Pressure Liquid , Vasculitis/diagnosis , Vasculitis/metabolism , Vasculitis/blood , Metabolomics/methods , Aged , Mass Spectrometry/methods , IgA Vasculitis/diagnosis , IgA Vasculitis/blood , IgA Vasculitis/metabolism
18.
Arch Dermatol Res ; 316(6): 268, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795175

ABSTRACT

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by ulcerative painful lesions with violaceous undermined borders. Up to 75% of PG cases develop in association with an underlying systemic disease. Monoclonal gammopathy is reportedly a concomitant condition with PG, with studies indicating immunoglobulin (Ig) A gammopathy as the most common. Whether gammopathy is associated with PG or is an incidental finding has been debated. We sought to investigate the association and characteristics of gammopathy in patients with PG. We retrospectively identified PG patients at our institution from 2010 to 2022 who were screened for plasma cell dyscrasia. Of 106 patients identified, 29 (27%) had a gammopathy; subtypes included IgA (41%), IgG (28%), and biclonal (IgA and IgG) (14%). Mean age was similar between those with and without gammopathy (60.7 vs. 55.9 years; P = .26). In addition, hematologic or solid organ cancer developed in significantly more patients with vs. without gammopathy (8/29 [28%] vs. 5/77 [6%]; P = .003). Among the subtypes of gammopathy, IgG monoclonal gammopathy had the highest proportion of patients with subsequent cancer development (4 of 8 patients, 50%). Study limitations include a retrospective, single-institution design with a limited number of patients. Overall, our data show a high prevalence of gammopathy in patients with PG; those patients additionally had an increased incidence of cancer, especially hematologic cancer.


Subject(s)
Paraproteinemias , Pyoderma Gangrenosum , Humans , Pyoderma Gangrenosum/diagnosis , Pyoderma Gangrenosum/epidemiology , Retrospective Studies , Middle Aged , Female , Male , Paraproteinemias/complications , Paraproteinemias/diagnosis , Paraproteinemias/epidemiology , Paraproteinemias/immunology , Aged , Immunoglobulin A/blood , Immunoglobulin A/immunology , Adult , Immunoglobulin G/blood , Immunoglobulin G/immunology
19.
Rheumatol Int ; 44(7): 1353-1357, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38739223

ABSTRACT

IgA-associated vasculitis (IgAV) known as Henoch - Schönlein purpura (HSP) disease is an inflammatory disorder of small blood vessels. It's the most common type of systemic vasculitis in children which can be associated with the inflammatory process following infections. IgA vasculitis is a rare and poorly understood systemic vasculitis in adults. Coronavirus disease 2019 (COVID-19) has been associated with HSP in both adults and children. A 58-year-old woman was diagnosed with HSP, fulfilling the clinical criteria: palpable purpura, arthritis, hematuria. The disclosure of the HSP disease was preceded by a infection of the respiratory tract. COVID-19 infection was confirmed via the presence of IgM and IgG antibodies. This case indicates the possible role of SARS-CoV-2 in the development of HSP. The clinical course of IgAV in adults appears to be different from pediatric IgAV, especially due to higher risk of renal complications. Symptoms of the disease quickly resolved with low-dose of steroids.


Subject(s)
COVID-19 , IgA Vasculitis , SARS-CoV-2 , Humans , COVID-19/complications , COVID-19/immunology , IgA Vasculitis/immunology , IgA Vasculitis/diagnosis , IgA Vasculitis/complications , IgA Vasculitis/drug therapy , Female , Middle Aged , SARS-CoV-2/immunology , Immunoglobulin A/blood , Immunoglobulin A/immunology
20.
Rev Assoc Med Bras (1992) ; 70(4): e20231120, 2024.
Article in English | MEDLINE | ID: mdl-38716937

ABSTRACT

OBJECTIVE: We aimed to examine the effect of remission status on thiol-disulfide homeostasis in celiac patients and thus to indirectly determine the effect of oxidative stress and inflammation caused by non-compliance with the diet. METHODS: Between February 2019 and December 2021, 117 patients diagnosed with celiac disease were included in this prospective randomized and controlled study. In addition to routine tests of celiac patients, thiol and disulfide measurements were made from the blood both at the beginning of the study and at the end of the first year. RESULTS: While 52 of the patients (44.4%) were in remission, 65 patients (55.6%) were not. There was an evident increase in native thiol levels of the patients who were initially not in remission but went into at the end of the first year (347.4±46.7 µmol/L vs. 365.3±44.0 µmol/L; p=0.001). Mean plasma disulfide levels of patients with celiac going into remission became reduced in the first year from the level of 14.5±5.1 µmol/L down to 8.9±4.2 µmol/L (p<0.001). In celiac patients who entered remission, disulfide and anti-tissue transglutaminase immunoglobulin A levels decreased in a correlation (r=0.526; p<0.001). CONCLUSION: Not being in remission in celiac disease leads to increased oxidative stress, and thiol-disulfide homeostasis is an indirect indicator of this. Additionally, providing remission in celiac patients reduces oxidative stress.


Subject(s)
Celiac Disease , Diet, Gluten-Free , Disulfides , Oxidative Stress , Patient Compliance , Sulfhydryl Compounds , Humans , Celiac Disease/diet therapy , Celiac Disease/blood , Oxidative Stress/physiology , Female , Male , Disulfides/blood , Prospective Studies , Sulfhydryl Compounds/blood , Adult , Remission Induction , Young Adult , Adolescent , Middle Aged , Immunoglobulin A/blood , Transglutaminases/blood
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