ABSTRACT
OBJECTIVE: Rheumatoid arthritis (RA) is characterised by the presence of autoantibodies, among which those targeting the constant region of immunoglobulin G (IgG), called rheumatoid factors (RF). Despite this link, RFs can also be found in other disorders and the healthy population, which hampers its use as a diagnostic tool. We recently showed that a subset of RA-derived RFs target a distinct epitope on the IgG-Fc, a feature that is currently not used in the clinic. METHODS: We determined immunoglobulin M (IgM)-RF levels specific against an RA-associated epitope (using our engineered next-generation RF antigen 'T3-17') in a prospective cohort of 475 patients with seropositive (for IgM-RF or aCCP) arthralgia that were followed for 5 years or until the development of arthritis. RESULTS: The presence of RFs targeting T3-17 was more strongly associated with progression to arthritis in comparison to traditional RF measurements. Within the group of patients positive for T3-17 RF the risk of arthritis development was increased as compared with wild-type RF, HR=3.2 (95% CI 2.4 to 4.3) vs HR=2.2 (95% CI 1.7 to 3.0). Predictive power of T3-17 RF was improved in combination with aCCP titres, HR=6.4 (4.7-8.7) vs HR=5.1 (3.9-6.8). This combination performed better than aCCP detection on its own. CONCLUSION: The detection of disease-specific RF is feasible and seems to improve the diagnostic power of RF and should be considered to be implemented in the clinic.
Subject(s)
Arthritis, Rheumatoid , Biomarkers , Rheumatoid Factor , Humans , Rheumatoid Factor/blood , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/blood , Male , Female , Middle Aged , Aged , Autoantibodies/blood , Immunoglobulin M/blood , Prospective Studies , Adult , Disease Progression , Epitopes/immunology , Prognosis , Immunoglobulin G/blood , Immunoglobulin G/immunologyABSTRACT
Point-of-care serological and direct antigen testing offers actionable insights for diagnosing challenging illnesses, empowering distributed health systems. Here, we report a POC-compatible serologic test for Lyme disease (LD), leveraging synthetic peptides specific to LD antibodies and a paper-based platform for rapid, and cost-effective diagnosis. Antigenic epitopes conserved across Borrelia burgdorferi genospecies, targeted by IgG and IgM antibodies, are selected to develop a multiplexed panel for detection of LD antibodies from patient sera. Multiple peptide epitopes, when combined synergistically with a machine learning-based diagnostic model achieve high sensitivity without sacrificing specificity. Blinded validation with 15 LD-positive and 15 negative samples shows 95.5% sensitivity and 100% specificity. Blind testing with the CDC's LD repository samples confirms the test accuracy, matching lab-based two-tier results, correctly differentiating between LD and look-alike diseases. This LD diagnostic test could potentially replace the cumbersome two-tier testing, improving diagnosis and enabling earlier treatment while facilitating immune monitoring and surveillance.
Subject(s)
Antibodies, Bacterial , Borrelia burgdorferi , Immunoglobulin G , Immunoglobulin M , Lyme Disease , Sensitivity and Specificity , Serologic Tests , Lyme Disease/diagnosis , Lyme Disease/immunology , Lyme Disease/blood , Lyme Disease/microbiology , Humans , Serologic Tests/methods , Borrelia burgdorferi/immunology , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Antigens, Bacterial/immunology , Machine Learning , Epitopes/immunology , Point-of-Care Testing , Point-of-Care SystemsABSTRACT
Guillain-Barré syndrome and neuralgic amyotrophy have been associated with hepatitis E virus (HEV) genotype 3 infections, while myasthenia gravis (MG) has been associated with HEV genotype 4 infections. However, whether chronic inflammatory demyelinating polyneuropathy (CIDP) is associated with HEV infections has not been conclusively clarified yet. 102 CIDP patients, 102 age- and sex-matched blood donors, 61 peripheral neuropathy patients (non-CIDP patients), and 26 MG patients were tested for HEV and anti-HEV IgM and IgG. Sixty-five of the 102 (64%) CIDP patients tested positive for anti-HEV IgG and one (1%) for anti-HEV IgM. No other patient tested positive for ati-HEV IgM. In the subgroup of CIDP patients with initial diagnosis (without previous IVIG treatment), 30/54 (56%) tested positive for anti-HEV IgG. Anti-HEV rates were significantly lower in blood donors (28%), non-CIDP peripheral neuropathy patients (20%), and MG patients (12%). No subject tested positive for HEV viremia. CSF tested negative for in 61 CIDP patients (54 patients with primary diagnosis). The development of CIDP but not non-CIDP polyneuropathy may be triggered by HEV exposure in an HEV genotype 3 endemic region. The increased anti-HEV seroprevalence in CIDP patients is not a consequence of IVIG therapy.
Subject(s)
Hepatitis E virus , Hepatitis E , Immunoglobulin G , Immunoglobulin M , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Humans , Male , Female , Hepatitis E/complications , Hepatitis E/blood , Hepatitis E/immunology , Middle Aged , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/blood , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnosis , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/immunology , Adult , Aged , Hepatitis E virus/immunology , Immunoglobulin G/blood , Immunoglobulin M/blood , Hepatitis Antibodies/bloodABSTRACT
Shortly after the emergence of newly formed human B cells from bone marrow as transitional cells, they diverge along two developmental pathways that can be distinguished by the level of IgM they express and migratory biases. Here, we propose that differential tissue homing of immature B cell subsets contributes to human lymphoid tissue structure and function.
Subject(s)
Cell Movement , Lymphoid Tissue , Humans , Lymphoid Tissue/immunology , Lymphoid Tissue/cytology , Cell Movement/immunology , B-Lymphocytes/immunology , Immunoglobulin M/metabolism , Immunoglobulin M/immunology , B-Lymphocyte Subsets/immunology , Precursor Cells, B-Lymphoid/immunology , Precursor Cells, B-Lymphoid/cytology , Cell Differentiation/immunologyABSTRACT
Hepatitis Delta Virus (HDV), a satellite virus of Hepatitis B virus, exacerbates liver damage in affected individuals. Screening for HDV antibodies in HBsAg positive patients is recommended, but the diagnostic accuracy of serological tests remains uncertain. This review aimed to assess the diagnostic accuracy of serological tests for HDV. We searched PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Scopus etc. for relevant studies. Studies measuring the sensitivity and specificity of serological HDV tests against PCR as a reference standard were included. Pooled sensitivity and specificity for each test method and sero-marker were calculated. The review included six studies with 11 study arms, evaluating ARCHITECT immunoassay, EIA, ELISA, QMAC, RIA, and Western Blot test methods targeting Anti-HDV IgG, Total anti-HDV and Anti-HDV IgM. Sensitivities for Anti-HDV IgG, Total Anti-HDV and Anti-HDV IgM, tests were 97.4%, 51.9%, and 62.0%, respectively, with specificities of 95.3%, 80.0%, and 85.0%. Our findings, with its limited number of studies, suggest that HDV serological tests, particularly those identifying Anti IgG exhibit high accuracy and can serve as effective screening tools for HDV.
Subject(s)
Hepatitis D , Hepatitis Delta Virus , Sensitivity and Specificity , Serologic Tests , Humans , Hepatitis Delta Virus/immunology , Hepatitis D/diagnosis , Hepatitis D/virology , Hepatitis D/blood , Hepatitis D/immunology , Serologic Tests/methods , Serologic Tests/standards , Immunoglobulin G/blood , Hepatitis Antibodies/blood , Immunoglobulin M/bloodABSTRACT
INTRODUCTION: Query (Q) fever is a zoonosis caused by the bacterium Coxiella burnetii typically presenting as an influenza-like illness (ILI) with or without hepatitis. The infection may be missed by clinicians in settings of low endemicity, as the presentation is clinically not specific, and there are many more common differential diagnoses for ILI including SARS-CoV-2 infection. METHODS: Residual serum samples were retrospectively tested for Phase 1 and 2 Q fever-specific IgM, IgG, IgA antibodies by indirect immunofluorescence and C. burnetii DNA by polymerase chain reaction. They had not been previously tested for Q fever, originating from undiagnosed patients with probable ILI, aged 10-70 years and living in regional New South Wales, Australia. The results were compared with contemperaneous data on acute Q fever diagnostic tests which had been performed based on clinicians requests from a geographically similar population. RESULTS: Only one (0.2%) instance of missed acute Q fever was identified after testing samples from 542 eligible patients who had probable ILI between 2016-2023. Laboratory data showed that during the same period, 731 samples were tested for acute Q fever for clinician-initiated requests and of those 70 (9.6%) were positive. Probability of being diagnosed with Q fever after a clinician initiated request was similar regardless of the patients sex, age and the calendar year of sampling. CONCLUSION: In this sample, Q fever was most likely to be diagnosed via clinician requested testing rather than by testing of undiagnosed patients with an influenza like illness.
Subject(s)
Coxiella burnetii , Influenza, Human , Q Fever , Humans , Q Fever/diagnosis , Q Fever/epidemiology , New South Wales/epidemiology , Middle Aged , Adult , Adolescent , Male , Aged , Female , Young Adult , Child , Influenza, Human/epidemiology , Influenza, Human/diagnosis , Influenza, Human/virology , Retrospective Studies , Coxiella burnetii/genetics , Coxiella burnetii/isolation & purification , Coxiella burnetii/immunology , Antibodies, Bacterial/blood , Diagnosis, Differential , COVID-19/diagnosis , COVID-19/epidemiology , Immunoglobulin M/bloodABSTRACT
Leprosy continues to pose a significant challenge to public health, particularly in certain global regions. Accurate diagnosis and understanding of the disease's etiology are crucial for effective management and prevention. This study aimed to explore the contribution of Natural resistance-associated macrophage protein 1 (NRAMP1) and its genetic variations, as well as the levels of anti-PGL-1 antibodies, to the pathology of multibacillary leprosy in affected individuals and their household contacts. The study included 23 multibacillary leprosy patients and 28 household contacts. NRAMP1 protein expression and anti-PGL-1 IgG and IgM levels were measured using PCR and ELISA techniques, respectively. Genotypic variants of the NRAMP1 gene were also examined. Statistical analyses, including Mann-Whitney tests and univariate logistic regression, were employed to evaluate the data. Significant differences were observed in NRAMP1 protein expression and IgG and IgM levels between the patient and household contact groups. The study also highlighted the role of the NRAMP1 gene and its D543N and 3'UTR polymorphisms in leprosy susceptibility. No significant differences were observed in the genotype variants of INT4 between the two groups. These findings emphasize the potential of integrating PCR technology with serological tests to enhance diagnostic precision in leprosy. They also suggest the need for further research to clarify the role of NRAMP1 and its polymorphisms in leprosy susceptibility and resistance.
Subject(s)
Antibodies, Bacterial , Antigens, Bacterial , Cation Transport Proteins , Glycolipids , Immunoglobulin M , Leprosy, Multibacillary , Humans , Male , Leprosy, Multibacillary/genetics , Female , Adult , Immunoglobulin M/blood , Antibodies, Bacterial/blood , Cation Transport Proteins/genetics , Middle Aged , Antigens, Bacterial/immunology , Antigens, Bacterial/genetics , Immunoglobulin G/blood , Young Adult , Genotype , Adolescent , Family Characteristics , Gene Expression , Mycobacterium leprae/immunology , Mycobacterium leprae/geneticsABSTRACT
BACKGROUND: Toxoplasma gondii (T. gondii) is a ubiquitous protozoan parasite on our planet that causes toxoplasmosis. This study evaluated the seroprevalence and related risk factors for T. gondii infection in a population referred to healthcare centers in Meshkin-Shahr, Northwest Iran. METHODS: A total of 400 blood samples were randomly collected from the general population and assessed using the anti-Toxoplasma antibodies, Immunoglobulin G and M (IgG and IgM) Enzyme-linked immunosorbent assay (ELISA) Kits in two steps before and during the coronavirus disease 2019 (COVID-19) pandemic, 2019-2020. The results were analyzed through logistic regression via SPSS 26 software. RESULTS: Before the COVID-19 pandemic, anti-toxoplasma antibodies were detected in 39% of individuals (IgG: 38%, IgM: 0.5%, and IgG-IgM: 0.5%). Among the eleven risk factors evaluated, contact with soil and people awareness were significantly associated with T. gondii infection (p < 0.05). However, factors such as females, 20-39 age groups, junior high schools, housewives, rural areas, raw meat or vegetable consumption, vegetable or fruits washed by water, not detergent, and cat owners did not show a significant relationship with seropositivity (p > 0.05). After the outbreak of the COVID-19 pandemic, the overall seroprevalence for anti-T. gondii antibody increased to 49.7% (IgG: 47.7%, IgM: 0.5%, and IgG and IgM: 1.5%). Among these patients, 26% were positive for COVID-19. Additionally, before the COVID-19 pandemic, 40 samples were negative for anti-T. gondii antibodies but later became positive. The crude and adjusted models suggested that toxoplasmosis may be a possible risk factor for increased susceptibility to COVID-19, with an odds ratio (OR) of 1.28 (95% confidence interval (CI), 0.82-1.99; P < 0.05). Conversely, a non-significant protective effect against latent toxoplasmosis was observed in COVID-19-positive individuals (OR = 0.99; 95% CI, 0.51-1.92; P > 0.05), and COVID-19 positivity did not increase the levels of anti-T. gondii IgG antibodies. CONCLUSIONS: The general population in this region had a moderate seroprevalence of T. gondii. The increased number of COVID-19-positive patients with latent toxoplasmosis highlights the need to pay attention to the early diagnosis and proper treatment of toxoplasmosis in these patients and implement preventive programs in these areas for future possible viral infections.
Subject(s)
Antibodies, Protozoan , COVID-19 , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2 , Toxoplasma , Toxoplasmosis , Humans , COVID-19/epidemiology , COVID-19/immunology , Iran/epidemiology , Seroepidemiologic Studies , Toxoplasmosis/epidemiology , Female , Male , Adult , Toxoplasma/immunology , Middle Aged , Young Adult , Immunoglobulin G/blood , Risk Factors , Immunoglobulin M/blood , Antibodies, Protozoan/blood , SARS-CoV-2/immunology , Adolescent , Aged , Child , Prevalence , Enzyme-Linked Immunosorbent Assay , Child, Preschool , PandemicsABSTRACT
A typographical error in the Reference No. 175 appeared erroneously in the References List of the article titled "Anti- SARSCoV- 2 IgG and IgM Levels in Iraqi General Population", 2023; 22(2) [1]. Original: Barassi, A.; Pezzilli, R.; Mondoni, M.; Rinaldo, R.F.; Dav, I.M.; Cozzolino, M. Vitamin D in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with non-invasive ventilation support. Panminerva Med., 2021, â¢â¢â¢ Corrected: Barassi, A.; Pezzilli, R.; Mondoni, M.; Rinaldo, R.F.; Davì, M.; Cozzolino, M. Vitamin D in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients with non-invasive ventilation support. Panminerva Med., 2023, 65(1), 23-29. We apologize to the readers for the inconvenience caused due to this error. The original article can be found online at: https://www.eurekaselect.com/article/135111.
Subject(s)
COVID-19 , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2 , Humans , Immunoglobulin M/blood , Immunoglobulin M/immunology , Iraq , COVID-19/immunology , SARS-CoV-2/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunologyABSTRACT
BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) led to a major global health crisis, leading to a worldwide pandemic. Several therapeutic interventions have been tried with varied results. The purpose of this academic work was to assess the efficacy of immunoglobulin M (IgM)-enriched Ig in the management of patients with severe COVID-19 pneumonia. MATERIALS AND METHODS: In this retrospective cohort study, severe COVID-19 pneumonia patients who received IgM-enriched immunoglobulin, in addition to standard-of-care treatment, were retrospectively enrolled. Levels of inflammatory biomarkers, oxygenation status, and organ dysfunction were evaluated, and differences were noted after giving IgM-supplemented IgM. RESULTS: Data from 32 consecutive severe COVID-19 patients admitted to medical intensive care units (ICUs) were analyzed. After giving IgM-enriched Ig, there was an improvement in oxygenation indices as shown by saturation of oxygen/fraction of inspired oxygen (SpO2/FiO2) on days 3 and 7, but it was not statistically significant. Oxygen support could be de-escalated in 13 (40.6%) patients on day 3 and in 8 (25%) patients on day 7, after giving IgM-enriched Ig. After giving IgM-enriched Ig, there was a reduction in the levels of all the studied inflammatory markers [interleukin-6 (IL-6), D-dimer, and ferritin) on days 3 and 7, but it was statistically significant only for IL-6. The overall ICU mortality was 53.1%. CONCLUSION: Outcomes of patients with severe COVID-19 requiring ICU care remain dismal. IgM-enriched Ig may be helpful in improving oxygenation and combating cytokine storm in these patients. However, in the present study, the improvement in oxygenation indices (SpO2/FiO2) and reduction in inflammatory markers like D-dimer and ferritin were not statistically significant. Hence, larger randomized controlled trials are required to get more definitive evidence to support this therapy and show significant clinical and mortality benefits.
Subject(s)
COVID-19 , Immunoglobulin M , Humans , COVID-19/therapy , COVID-19/immunology , Retrospective Studies , Immunoglobulin M/blood , Male , Middle Aged , Female , Treatment Outcome , Adult , Aged , SARS-CoV-2 , Fibrin Fibrinogen Degradation Products/analysis , Intensive Care Units , Ferritins/blood , Interleukin-6/bloodABSTRACT
The significance of glomerular IgM deposit intensity in IgA Nephropathy (IgAN) remained ambiguous and requires further research. Patients with biopsy-proven IgAN in our hospital from January 2018 to May 2023 were recruited into this retrospective single-center study. Patients who presented with positive IgM deposit were included in IgM + cohort while patients with negative IgM deposit were included in IgM- cohort. Of the IgM+, patients whose IF intensity of IgM deposits exceeded 1+ formed IgM-H cohort while patients whose IF intensity of IgM deposits was equal to 1+ consisted IgM-L cohort. Pairwise comparisons were performed among these cohorts to determine clinical disparities, following the propensity score matching process. Among 982 IgAN patients, 539 patients presented with positive IgM deposit. The Kaplan-Meier analysis showed that the IgM deposit did not contribute adversely to the outcomes (eGFR decreased from the baseline ≥ 50% continuously or reached end-stage renal disease). However, the Cox regression analysis showed that increased intensity of IgM deposit was an independent risk factor (p = 0.03) in IgM+. The IgM-H exhibited more pronounced segmental glomerulosclerosis (p = 0.02) than the IgM-L, which may also be associated more directly with higher urine protein levels (p = 0.02). Moreover, our generalized linear mixed model demonstrated a remarkably higher urine albumin/creatinine ratio (p < 0.01) and serum creatinine (p = 0.04) levels as well as lower serum albumin (p < 0.01) level in IgM-H persistently during the 5-year follow-up. This study concluded that increased intensity of glomerular IgM deposits may contribute adversely to clinicopathologic presentation and outcome in those IgM + patients.
Subject(s)
Glomerular Filtration Rate , Glomerulonephritis, IGA , Immunoglobulin M , Kidney Glomerulus , Humans , Immunoglobulin M/blood , Male , Glomerulonephritis, IGA/immunology , Female , Retrospective Studies , Adult , Follow-Up Studies , Kidney Glomerulus/pathology , Kidney Glomerulus/immunology , Middle Aged , Risk Factors , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/immunology , Kaplan-Meier Estimate , Disease Progression , Biopsy , Clinical RelevanceABSTRACT
Cite this article as: Balaban YH, Ismail M, Nur Ayar S. Selective immunoglobulin M deficiency in patients with autoimmune liver diseases. Turk J Gastroenterol. 2024;35(6):505-508.
Subject(s)
Immunoglobulin M , Humans , Immunoglobulin M/blood , Immunoglobulin M/deficiency , Female , Male , Autoimmune Diseases/immunology , Autoimmune Diseases/complications , Liver Diseases/immunology , Liver Diseases/etiology , Middle Aged , Hepatitis, Autoimmune/complications , Hepatitis, Autoimmune/immunology , AdultABSTRACT
Background: Production of anti-phosphatidylserine (anti-PS) antibodies has been associated with malaria and can aggravate pathology. How these autoantibodies develop during early childhood in a malaria context is not known. We examined levels of anti-PS IgG and IgM antibodies in a longitudinal cohort of mother-baby pairs during birth, in the infants at 2.5, 6 months, and in mothers and their babies at 9 months postpartum. Results: There was no difference between levels of anti-PS IgG in cord blood and the mothers' peripheral blood at birth. However, anti-PS IgM levels were significantly higher in the mothers compared to the infants' cord blood, and IgM levels were steadily increasing during the first 9 months of the infants' life. In infants that had the highest anti-PS IgM levels at birth, there was a decline until 6 months with a rise at 9 months. Infants that possessed high anti-PS IgG at birth also exhibited a progressive decline in levels. When anti-PS were correlated to different fractions of B-cells, there were several correlations with P. falciparum specific atypical B cells both at birth and at 2.5 months for the infants, especially for anti-PS IgM. Anti-PS also correlated strongly to C1q-fixing antibodies at birth. Conclusion: These results show that anti-PS IgG acquired by mothers could be transferred transplacentally and that IgM antibodies targeting PS are acquired during the first year of life. These results have increased the knowledge about autoimmune responses associated with infections in early life and is critical for a comprehensive understanding of malaria vaccine functionality in endemic areas.
Subject(s)
Immunoglobulin G , Immunoglobulin M , Phosphatidylserines , Humans , Immunoglobulin M/blood , Immunoglobulin M/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Female , Phosphatidylserines/immunology , Infant , Uganda , Infant, Newborn , Adult , Plasmodium falciparum/immunology , Male , Malaria, Falciparum/immunology , Malaria, Falciparum/parasitology , Malaria, Falciparum/epidemiology , Immunity, Maternally-Acquired , Autoantibodies/immunology , Autoantibodies/blood , Antibodies, Protozoan/immunology , Antibodies, Protozoan/blood , Mothers , Fetal Blood/immunology , B-Lymphocytes/immunology , Longitudinal StudiesABSTRACT
BACKGROUND: Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death. METHODS: Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6-29) and 28-day all-cause mortality (Days 1-29). RESULTS: One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 109/L) at baseline. Forty-seven patients in the trimodulin group and 49 in the placebo group met these criteria. A difference of 15.5 percentage points in clinical deterioration and mortality was observed in favour of trimodulin (95% confidence interval: -4.46, 34.78; P = 0.096). CONCLUSION: Although there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation. ESSCOVID WAS REGISTERED PROSPECTIVELY AT CLINICALTRIALS.GOV ON OCTOBER 6, 2020.: NCT04576728.
Subject(s)
COVID-19 Drug Treatment , COVID-19 , Humans , Male , Female , Double-Blind Method , Middle Aged , Aged , COVID-19/mortality , COVID-19/therapy , Treatment Outcome , SARS-CoV-2 , Adult , Drug Combinations , Immunoglobulin A , Immunoglobulin G , Immunoglobulin MABSTRACT
BACKGROUND: Modified 2-tiered testing (MTTT) for Lyme disease utilizes automatable, high throughput immunoassays (AHTIs) in both tiers without involving western immunoblots, offering performance and practical advantages over standard 2-tiered testing (STTT; first-tier AHTI followed by immunoglobulin M (IgM) and immunoglobulin G (IgG) western immunoblots). For MTTT, Centers for Disease Control and Prevention recommends using AHTI test kits that have been cleared by Food and Drug Administration (FDA) specifically for this intended use. We evaluated performance of FDA-cleared MTTT commercial test kits from 3 manufacturers by comparing with STTT results. METHODS: We performed MTTT (total antibody AHTI with reflex to separate IgM and IgG AHTIs) using test kits from Diasorin, Gold Standard Diagnostics (GSD), and Zeus Scientific on 382 excess serum samples submitted to the clinical laboratory for routine Lyme disease serologic testing in July 2018, measuring agreement between MTTT and STTT using the κ statistic. RESULTS: Overall agreement with STTT was 0.87 (95% confidence interval [CI], .77-.97) using Diasorin assays (almost perfect agreement), 0.80 (95% CI, .68-.93) using GSD assays (substantial agreement) and 0.79 (95% CI, .68-.90) using Zeus assays (substantial agreement). For detection of IgM reactivity, agreement between MTTT and STTT was 0.70 (.51-.90; substantial), 0.63 (95% CI, .44-.82; substantial) and 0.56 (95% CI, .38-.73; moderate), respectively. For detection of IgG reactivity, MTTT/STTT agreement was 0.73 (95% CI,.58-.88), 0.78 (95% CI, .62-.94), and 0.75 (95% CI, .60-.90), respectively (substantial agreement in all cases). CONCLUSIONS: MTTT results obtained using commercial test kits from 3 different manufacturers had substantial to almost perfect agreement with STTT results overall and moderate to substantial agreement for IgM and IgG detection independently. Commercial MTTT tests can be used broadly for the diagnosis of Lyme disease.
Subject(s)
Antibodies, Bacterial , Immunoglobulin G , Immunoglobulin M , Lyme Disease , Reagent Kits, Diagnostic , Serologic Tests , Lyme Disease/diagnosis , Lyme Disease/immunology , Lyme Disease/blood , Humans , Serologic Tests/methods , Immunoglobulin G/blood , Immunoglobulin M/blood , Reagent Kits, Diagnostic/standards , Antibodies, Bacterial/blood , Algorithms , Sensitivity and Specificity , Immunoassay/methods , United States , Borrelia burgdorferi/immunology , Middle Aged , Adult , FemaleABSTRACT
BACKGROUND: Since March 2020, COVID-19 has evolved from a localized outbreak to a global pandemic. We assessed the seroprevalence of COVID-19 in three towns in the Centre Sud region of Burkina Faso. METHODS: A population-based cross-sectional survey was conducted in three middle-sized cities in Burkina Faso's Centre Sud region, from June to July 2021. Subjects aged 16 or over at the time of the survey were considered for this seroprevalence study. The Biosynex COVID-19 BSS rapid test was used to detect immunoglobulin G (IgG) and immunoglobulin M (IgM) against SARS-CoV-2. A standardized questionnaire was also administered to collect additional information. RESULTS: A total of 2449 eligible participants (age ≥ 16 years) were identified. Serological tests for COVID-19 were performed in 2155 individuals, of which 2143 valid tests were retained and analyzed. Out of the entire sample, 246 positive tests were observed, corresponding to a prevalence of 11.48%. Prevalence was 9.35% (58 cases) in Kombissiri, 12.86% (80 cases) in Manga and 11.99% (108 cases) in Pô. By gender, 13.37% of women (164 cases) tested positive, and 8.95% of men (82 cases). Women accounted for 66.67% of all positive test subjects. The results from the multivariate analysis show a significantly higher seroprevalence in women (p = 0.007), people over 55 years old (p = 0.004), overweight people (p = 0.026) and those with drinking water sources at home (p = 0.013). CONCLUSIONS: The results of this study show that the COVID-19 virus also circulates in the population of middle-sized cities in Burkina Faso, far more than officially reported by the information service of the government of Burkina Faso, given the lack of systematic testing in the general population in the country. The study also highlighted the greater vulnerability of women, older and overweight individuals to the epidemic. The preventive measures put in place to fight the pandemic must take these different factors into account.
Subject(s)
COVID-19 , Cities , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/blood , Burkina Faso/epidemiology , Female , Male , Adult , Seroepidemiologic Studies , Cross-Sectional Studies , Middle Aged , Risk Factors , Adolescent , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Cities/epidemiology , Young Adult , Immunoglobulin G/blood , Aged , Antibodies, Viral/blood , Immunoglobulin M/bloodABSTRACT
We evaluated the diagnostic performance of newly developed microfluidic microplate-based fluorescent ELISA for anti-SARS-CoV-2 antibody detection: the Veri-Q opti COVID-19 IgG and IgM ELISAs (hereafter, "Opti IgG/M"; MiCo BioMed, Gyeonggi-do, Republic of Korea), in comparison with conventional ELISAs. A total of 270 serum samples were analyzed, among which 90 samples were serially obtained from 25 COVID-19 patients. Another 180 samples were collected from 180 SARS-CoV-2-negative individuals. As comparative assays, we used SCoV-2 Detect IgG/M ELISA (hereafter, "InBios IgG/M"; InBios, Seattle, WA, USA) and Veri-Q COVID-19 IgG/IgM ELISA (hereafter, "Veri-Q IgG/M"; MiCo BioMed). Compared with conventional ELISAs, the Opti IgG yielded 97.1-100.0% positive percent agreement, 95.2-98.0% negative percent agreement, 96.3-97.8% total percent agreement, and kappa values of 0.90-0.94. Between the Opti IgM and the InBios IgM, the values were 93.7%, 96.6%, 95.9%, and 0.89, respectively. For the Opti IgG, sensitivities for the samples collected from 0-7, 8-14, 15-21, and ≥ 22 days after symptom onset were 40.0, 58.3, 94.1, and 100.0%, respectively. The values for the Opti IgM were 30.0, 54.2, 88.2, and 80%, respectively. The diagnostic specificities of the Opti IgG and IgM were 99.4 and 97.2%, respectively. The microfluidic microplate-based fluorescent ELISAs showed comparable diagnostic performance to conventional ELISAs for detecting anti-SARS-CoV-2 antibodies. With the combination of high throughput, a simplified workflow, and the ability to analyze reduced volumes, this new technology has great potential for improving SARS-CoV-2 serologic testing.
Subject(s)
Antibodies, Viral , COVID-19 Serological Testing , COVID-19 , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2 , Humans , Immunoglobulin M/blood , Immunoglobulin M/immunology , Immunoglobulin G/blood , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/blood , Enzyme-Linked Immunosorbent Assay/methods , COVID-19 Serological Testing/methods , Sensitivity and Specificity , Microfluidics/methods , Microfluidics/instrumentation , Middle Aged , Female , Male , AgedABSTRACT
OBJECTIVE: The study aimed to characterize serum immunoglobulin (Ig) concentrations and their relationship with clinical and paraclinical features in patients with COPD group E in the stable stage. Additionally, the study focused on evaluating the relationship between serum Ig levels and the risk of exacerbations over the next 12 months, thereby clarifying the role of serum Ig deficiency in affecting the future risk for these patients. METHODS: A prospective observational study assessed IgG, IgA, IgM, and IgE levels in 67 COPD patients and 30 healthy controls at Military Hospital 103 from October 2017 to August 2020. Primary outcomes included Ig isotype levels in COPD patients, with secondary outcomes exploring differences compared to controls and associations with clinical variables. RESULTS: COPD patients showed significantly lower IgG concentrations and higher IgA levels than controls. IgM and IgE levels did not differ significantly. Subgroup analysis revealed notable decreases in IgG1 and IgG3 concentrations, with 10.4% of patients exhibiting reduced IgG levels and 0.3% diagnosed with common variable immunodeficiency. No significant associations were found between Ig levels and exacerbation risk or clinical variables. CONCLUSIONS: Serum IgG and IgM concentrations were significantly reduced in COPD patients compared to normal individuals, with IgG1 and IgG3 concentrations notably low. Serum IgA levels were significantly higher in COPD patients compared with normal controls. However, no significant association was found between Ig concentrations, particularly serum IgG deficiency and its subclasses, with the frequency and risk of exacerbations during 12 months of longitudinal follow-up. Caution is warranted in the use of immunoglobulin therapy in the treatment of COPD patients. TRIAL REGISTRATION: An independent ethics committee approved the study (Ethics Committee of Military Hospital 103 (No. 57/2014/VMMU-IRB), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/immunology , Pulmonary Disease, Chronic Obstructive/therapy , Male , Female , Prospective Studies , Aged , Middle Aged , Immunoglobulin G/blood , Case-Control Studies , Immunoglobulin A/blood , Disease Progression , Immunoglobulins/blood , Immunoglobulin M/bloodABSTRACT
Introduction: Coronavirus Disease 2019 (COVID-19) is a severe respiratory illness caused by the RNA virus SARS-CoV-2. Globally, there have been over 759.4 million cases and 6.74 million deaths, while Ecuador has reported more than 1.06 million cases and 35.9 thousand deaths. To describe the COVID-19 pandemic impact and the vaccinations effectiveness in a low-income country like Ecuador, we aim to assess the seroprevalence of IgG and IgM antibodies against SARS-CoV-2 in a sample from healthy blood donors at the Cruz Roja Ecuatoriana. Methods: The present seroprevalence study used a lateral flow immunoassay (LFIA) to detect anti-SARS-CoV-2 IgG and IgM antibodies in months with the highest confirmed case rates (May 2020; January, April 2021; January, February, June, July 2022) and months with the highest vaccination rates (May, June, July, August, December 2021) in Quito, Ecuador. The IgG and IgM seroprevalence were also assessed based on sex, age range, blood type and RhD antigen type. The sample size was 8,159, and sampling was performed based on the availability of each blood type. Results: The results showed an overall IgG and IgM seroprevalence of 47.76% and 3.44%, respectively. There were no differences in IgG and IgM seroprevalences between blood groups and sex, whereas statistical differences were found based on months, age range groups, and RhD antigen type. For instance, the highest IgG seroprevalence was observed in February 2022 and within the 17-26 years age range group, while the highest IgM seroprevalence was in April 2021 and within the 47-56 years age range group. Lastly, only IgG seroprevalence was higher in RhD+ individuals while IgM seroprevalence was similar across RhD types. Discussion: This project contributes to limited data on IgG and IgM antibodies against SARS-CoV-2 in Ecuador. It suggests that herd immunity may have been achieved in the last evaluated months, and highlights a potential link between the RhD antigen type and COVID-19 susceptibility. These findings have implications for public health strategies and vaccine distribution not only in Ecuador but also in regions with similar characteristics.
Subject(s)
Antibodies, Viral , Blood Donors , COVID-19 , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/immunology , Ecuador/epidemiology , Immunoglobulin G/blood , Seroepidemiologic Studies , Immunoglobulin M/blood , Male , SARS-CoV-2/immunology , Adult , Blood Donors/statistics & numerical data , Antibodies, Viral/blood , Female , Middle Aged , Adolescent , Young Adult , Aged , PandemicsABSTRACT
A woman in her 40s known to have systemic lupus erythematosus presented with a maculopapular rash on her face, neck and chest following measles exposure. She had received a single-dose measles vaccine as a child in the 1970s and was therefore presumed to be immune, and thus not infectious. As a result, she was initially managed in an open bay. Measles virus IgM antibody in serum was undetectable; however, measles virus RNA was subsequently detected in throat swab by PCR, which is consistent with current infection. Measles is one of the most transmissible diseases in the world and cases are rising both in the UK and globally. Our case and literature review highlight the risk of vaccine failure in measles, especially in people who have not received two doses of the measles, mumps and rubella vaccine. It also highlights the challenges in diagnosing measles in previously vaccinated individuals.