Irregular erythrocyte antibodies among antenatal women and their neonatal outcome at a tertiary care hospital in Northern India

BackgroundRed blood cell alloimmunisation during the pregnancy is a significant cause for neonatal mortality and morbidity. This study was planned to determine the prevalence and specificity of irregular erythrocyte antibodies in antenatal mothers and their neonatal outcome.MethodsIn this observational study, blood grouping and red cell antibody screening of mothers were performed at first visit and after 28 weeks of gestation and positive cases were identified and followed up monthly till delivery by repeating antibody titre and middle cerebral artery—peak systolic velocity. After delivery of alloimmunised mothers, cord blood haemoglobin, bilirubin and direct antiglobulin tests (DAT) were analysed and further outcome of neonate was recorded.ResultsAmong 652 registered antenatal cases, 18 multigravida women were found to be alloimmunised, accounting to prevalence of 2.8%. Most common alloantibody identified was anti D (>70%) followed by anti-Lea, anti-C, anti-Leb, anti-E and anti-Jka. Only 47.7% Rh D negative women received anti-D prophylaxis during previous pregnancies or whenever indicated. DAT was positive in 56.2% of neonates. Among nine DAT positive neonates, two early neonatal deaths due to severe anaemia were observed following birth resuscitation. Four antenatal mothers required intrauterine transfusion in view of fetal anaemia while three neonates received double volume exchange transfusion and top up transfusions after birth.ConclusionsThis study emphasises importance of red cell antibody screening for all multigravida antenatal women at registration of pregnancy and additionally at 28 weeks or later in high-risk cases irrespective of RhD status.

Value of combined detection of PCA, ANCA, ASCA, AGA and ANA in early diagnosis of Gastrointestinal Diseases

Objectives: To investigate the positive detection rate and clinical application value of anti-parietal cell antibody (PCA), anti-neutrophil cytoplasmic antibody (ANCA), anti-Saccharomyces cerevisiae antibody (ASCA), anti-gliadin antibody (AGA) and anti-nuclear antibody (ANA) in patients visiting the Department of Gastroenterology. Methods: From January 2015 to June 2018, 1,083 patients receiving detection of PCA and other autoantibodies were selected from the Department of Gastroenterology of Baoding First Central Hospital. The positive detection rate of autoantibodies was statistically analyzed. The enumeration data were expressed as rate or constituent ratio, and the rates were compared between groups using the x2 test. Results: Among the 1,083 patients, the positive detection rate of ANA, ASCA, AGA, PCA and ANCA was 33.52%, 16.71%, 15.51%, 13.66% and 7.66%, respectively. The total positive detection rate was 62.8% (n = 680). Conclusion: The population with abdominal distension, chronic abdominal pain, diarrhea and other digestive system symptoms should be timely treated with combined detection of PCA, ANCA, ASCA, AGA and ANA, which is of important clinical application value for early diagnosis of gastrointestinal diseases and prevention of missed diagnosis and misdiagnosis. doi: https://doi.org/10.12669/pjms.38.1.4682 How to cite this:Liu X, Guo D, Li X, Guo Y, Song W. Value of combined detection of PCA, ANCA, ASCA, AGA and ANA in early diagnosis of Gastrointestinal Diseases. Pak J Med Sci. 2022;38(1):---------. doi: https://doi.org/10.12669/pjms.38.1.4682 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Severe Hemolytic Disease of Newborn Due to Alloimmune Anti-E Antibodies: A Case Report

Hemolytic disease in the newborn (HDN) as a cause of early jaundice is mostly due to Rh (D), ABO incompatibility, and rarely due to other minor blood group incompatibility. We report case of Rh anti-E isoimmunization presenting as significant unconjugated jaundice within the 24 h of life. Baby presented with severe jaundice and anemia on day 1 of life. Baby was treated with intensive phototherapy, double volume exchange transfusion (DVET), and intravenous immunoglobulins. On evaluation, both mother and baby had O positive (Rh) blood group; however, the infant showed evidence of severe hemolysis. Positive direct Coombs test (DCT) and 11 cell antibody panel showed anti-E antibodies. This case highlights the importance of early identification and evaluation of HDN in the absence of Rh(D) and ABO incompatibility and possibility of severe hemolysis in Rh anti-E isoimmunization needing DVET.

Factors Associated with Seroconversion after COVID-19 Vaccination in Patients with Hematologic Malignancies

Background: Recent studies reported low rates of seroconversion response to COVID-19 vaccination in patients (pts) with hematologic malignancies (HMs). Vaccine choice among the 3 FDA-authorized products (BNT162b2/Pfizer-BioNTech, mRNA-1273/Moderna, or Ad26.COV2.S/J&J), prior therapy, and disease-specific factors may affect seroconversion. Addressing these factors may improve seroconversion rates and identify pts at risk of severe COVID-19 infection despite vaccination. Methods: We conducted a retrospective study of adults with HMs vaccinated in our center between 2/2021 and 7/2021, excluding pts with prior COVID-19 infection. Seroconversion was assessed by the qualitative SARS-CoV-2 Total Antibody Test (IgG/IgM against Receptor Binding Domain [RBD], Wondfo USA, Willowbrook, IL). A subset of samples was tested by the semi-quantitative Abbott AdviseDx SARS-CoV-2 IgG II assay (IgG against RBD). For univariate associations (UVA) we used Fisher's exact test for categorical variables, and fractional polynomial fits for continuous variables to examine non-linearity. Multivariable analysis (MVA) used a robust Poisson model reporting risk ratio (RR) with 95% confidence intervals (CI). Results: Among 239 eligible pts, median age was 70 (range, 28-94), and 112 (47%) were female. HMs included aggressive B-cell lymphomas (n=74, 31%), indolent B-cell lymphomas (n=52, 22%), chronic lymphocytic leukemia (CLL, n=30, 13%), other lymphomas (n-19, 8%), plasma cell neoplasms (n=43, 18%), and myeloid cancers (n=21, 9%); 140 pts (59%) received BNT162b2/Pfizer, 74 (31%) mRNA-1273/Moderna, and 23 (10%) Ad26.COV2.S/J&J vaccines (2 pts had undetermined vaccine type). HM was active in 100 pts (42%), whereas 108 (45%) pts were in remission after treatment, and 31 (13%) on watchful waiting (WW, never treated); 141 (59%) had a prior exposure to an anti-B-cell monoclonal antibody, and 22 (9%) prior stem cell transplantation. Overall, 99 pts (41%; binomial 95% CI, 35-48%) showed post-vaccination seroconversion upon testing at median 10 weeks from first vaccine. Seroconversion was significantly less frequent among pts with lymphomas compared with plasma cell or myeloid neoplasms (overall P=.020; Fig A). It was also less frequent after prior anti-B-cell antibody exposure (29% vs 59%, P<.0001; Fig. B), and in those with active disease (28%, vs 49% for remission [P=.0027], vs 58% for WW [P=.0045]; Fig. C). Furthermore, seroconversion was significantly more frequent after mRNA-1273/Moderna vaccine (57%) compared with BNT162b2/Pfizer (36%, P=.006) or Ad26.COV2.S/J&J (22%, P=.004; Fig. D). It was not associated with age (Fig. E), WBC (Fig. G), or time from vaccination (Fig. I), but was significantly higher with increased lymphocyte count (P<.0001; Fig F) and time elapsed from last chemotherapy (P=.0039; Fig. H). In a MVA (Fig. J), vaccination with mRNA-1273 remained significantly associated with higher rate of seroconversion compared with BNT162b2 (RR=0.59; 95%CI, 0.44-0.79) or Ad26.COV2.S (RR=0.35; 95%CI, 0.16-0.77). Higher seroconversion rate was also associated with remission (RR=1.98; 95%CI, 1.42-2.76) or WW status (RR=1.72; 95%CI 1.02-2.89) compared with active disease, and higher lymphocyte count. Exposure to anti-B-cell antibodies remained associated with lack of seroconversion (RR=0.66; 95%CI, 0.44-0.99). Seroconversion was borderline less frequent in CLL than lymphomas, and higher with plasma cell or myeloid disorders. Results were similar in the subset of pts (n=191) with prior treatment, adjusting for time from last chemotherapy(data not shown). The anti-COVID-19 IgG titers on semiquantitative test (n=47, all after mRNA-based vaccines) were also lower in pts with active disease compared with those in remission (P=.065) or under WW (P=.028), and in those with prior anti-B-cell antibody (P=.0095). Conclusions: Pts with HMs demonstrate overall low rates of seroconversion after vaccination against COVID-19, particularly when they have active disease or are on/after B-cell depleting monoclonal antibody therapy. The mRNA vaccines (particularly mRNA-1273) appear to have elicited superior responses compared with the adenovirus-based product. Pts with active HMs or those within 2 years of last therapy should be particularly aware of the risk of infection despite vaccines and should be considered for strategies to enhance anti-COVID-19 immunity regardless of age. Figure 1 Figure 1. Disclosures Olszewski: TG Therapeutics: Research Funding; PrecisionBio: Research Funding; Celldex Therapeutics: Research Funding; Acrotech Pharma: Research Funding; Genentech, Inc.: Research Funding; Genmab: Research Funding.

Proteo-Genomic Analysis Identifies Two Major Sites of Vulnerability on Ebolavirus Glycoprotein for Neutralizing Antibodies in Convalescent Human Plasma

Three clinically relevant ebolaviruses – Ebola (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) viruses, are responsible for severe disease and occasional deadly outbreaks in Africa. The largest Ebola virus disease (EVD) epidemic to date in 2013-2016 in West Africa highlighted the urgent need for countermeasures, leading to the development and FDA approval of the Ebola virus vaccine rVSV-ZEBOV (Ervebo®) in 2020 and two monoclonal antibody (mAb)-based therapeutics (Inmazeb® [atoltivimab, maftivimab, and odesivimab-ebgn] and Ebanga® (ansuvimab-zykl) in 2020. The humoral response plays an indispensable role in ebolavirus immunity, based on studies of mAbs isolated from the antibody genes in peripheral blood circulating ebolavirus-specific human memory B cells. However, antibodies in the body are not secreted by circulating memory B cells in the blood but rather principally by plasma cells in the bone marrow. Little is known about the protective polyclonal antibody responses in convalescent plasma. Here we exploited both single-cell antibody gene sequencing and proteomic sequencing approaches to assess the composition of the ebolavirus glycoprotein (GP)-reactive antibody repertoire in the plasma of an EVD survivor. We first identified 1,512 GP-specific mAb variable gene sequences from single cells in the memory B cell compartment. Using mass spectrometric analysis of the corresponding GP-specific plasma IgG, we found that only a portion of the large B cell antibody repertoire was represented in the plasma. Molecular and functional analysis of proteomics-identified mAbs revealed recognition of epitopes in three major antigenic sites - the GP head domain, the glycan cap, and the base region, with a high prevalence of neutralizing and protective mAb specificities that targeted the base and glycan cap regions on the GP. Polyclonal plasma antibodies from the survivor reacted broadly to EBOV, BDBV, and SUDV GP, while reactivity of the potently neutralizing mAbs we identified was limited mostly to the homologous EBOV GP. Together these results reveal a restricted diversity of neutralizing humoral response in which mAbs targeting two antigenic sites on GP – glycan cap and base – play a principal role in plasma-antibody-mediated protective immunity against EVD.

THE BANALITY OF IMMUNITY, DEATH AND DISTRESS OF TOBACCO SMOKING --("STRIKE THE RIGHT”)

WHO stated that Tobacco Control is "To protect present and future generations from the devastating health, social, environmental and out-turn of exposure to tobacco smoke”. Tobacco plants are indigenous to American abstinent and they knew of its cultivation thousands of years ago. Christopher Columbus brought this plant to European countries. Portuguese traders brought tobacco plants to India Tobacco put to use in the forms of smoking, chewing, or snorting. Bronchial accounts for more than 50% of all male deaths from malignant disease. It is four times more common in men than in women. Cigarette smoking for most cases of bronchial carcinoma, and the increased risk is directly proportional to the amount smoked and to the tar content of the cigarettes. Smoking puffs of any kind, disclosed to nicotine, have pernicious consequences on immune system. Nicotine escalates cortisol concentration, while curtail B cell antibody development and T cells' response to antigens. Smoking bumps one and the other innate and adaptive immunity and operates challenge roles in synchronize immunity