Antibodies In Plasma Research Articles

Antiphospholipid antibodies in patients with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by recurrent pregnancy morbidity or thrombosis in combination with the persistent presence of antiphospholipid antibodies (aPLs) in plasma/serum. Antiphospholipid antibodies are a heterogeneous, overlapping group of autoantibodies, of which anti-β2-glycoprotein I (aβ2GPI), anticardiolipin (aCL) antibodies and antibodies that prolong plasma clotting time in tests in vitro known as lupus anticoagulant (LAC) are included in the laboratory criteria for the diagnosis of APS. The presence of LAC antibodies in plasma is indirectly determined by measuring the length of coagulation in two tests - activated partial thromboplastin time (aPTT) and diluted Russell's viper venom time (dRVVT). The concentration of aβ2GPI and aCL (immunglobulin G (IgG) and immunoglobulin M (IgM) isotypes) in serum is directly determined by solid-phase immunoassays, either by enzyme-linked immunosorbent assay (ELISA), fluoroimmunoassay (FIA), immunochemiluminescence (CLIA) or multiplex flow immunoassay (MFIA). For patient safety, it is extremely important to control all three phases of laboratory testing, i.e. preanalytical, analytical and postanalytical phase. Specialists in laboratory medicine must be aware of interferences in all three phases of laboratory testing, in order to minimize these interferences. The aim of this review was to show the current pathophysiological aspects of APS, the importance of determining aPLs-a in plasma/serum, with an emphasis on possible interferences that should be taken into account when interpreting laboratory findings.

Controversies in COVID-19 pandemic: the case of convalescent plasma

The SARS-CoV-2 pandemic has caused an unprecedented health and social crisis worldwide. In this paper we summarized the different therapeutic actions planned from the two sides of the Atlantic Ocean (USA and Europe) to fight the initial phase of COVID-19 pandemic, with an emphasis on passive immunotherapies such as convalescent plasma and anti-Spike monoclonal antibodies. The lessons derived from the critical analysis of that period could drive our treatment decisions for the next pandemics.

Anti-A and anti-B titers in A, B and O whole blood donors: Beyond “dangerous O”

Background and ObjectivesHemolytic transfusion reactions (HTRs) pose significant risks in transfused patients, with anti-A and anti-B antibodies in donor plasma being potential contributing factors. Despite advancements in component preparation, HTRs remain a concern, particularly with apheresis-derived platelets. This study aimed to determine the prevalence of high anti-A and anti-B titers among A, B, and O blood group donors and to explore factors associated with high titers. Materials and MethodsA cross-sectional observational study was conducted over 18 months, enrolling 978 participants from a tertiary care teaching hospital in Western India. Anti-A and anti-B titers were determined using the Conventional Tube Technique (CTT). Statistical analysis assessed correlations between high titers and demographic factors. ResultsThe majority of participants were young males (98.8%). Prevalence of high titers for IgM anti-A was 12.2% and IgG anti-A was 2.5%. For anti-B, IgM titers were 2.3% and IgG titers were 0.2%. The prevalence of dangerous O was found to be 14.1%, while 3.52% and 10.5% of A and B blood group donors were found to have high titers, respectively. Factors associated with high titers included female gender, vegetarian diet, age <30 years, and O blood group. ConclusionThe study sheds additional light and provides supplementary information regarding the prevalence and correlation of high anti-A and anti-B titers among O, A and B blood donors. Understanding these factors is crucial for optimizing transfusion safety protocols, including selective screening of platelet units and tailored transfusion strategies based on donor characteristics.

A reduced proteomic signature in critically ill Covid-19 patients determined with plasma antibody micro-array and machine learning

BackgroundCOVID-19 is a complex, multi-system disease with varying severity and symptoms. Identifying changes in critically ill COVID-19 patients’ proteomes enables a better understanding of markers associated with susceptibility, symptoms, and treatment. We performed plasma antibody microarray and machine learning analyses to identify novel proteins of COVID-19.MethodsA case-control study comparing the concentration of 2000 plasma proteins in age- and sex-matched COVID-19 inpatients, non-COVID-19 sepsis controls, and healthy control subjects. Machine learning was used to identify a unique proteome signature in COVID-19 patients. Protein expression was correlated with clinically relevant variables and analyzed for temporal changes over hospitalization days 1, 3, 7, and 10. Expert-curated protein expression information was analyzed with Natural language processing (NLP) to determine organ- and cell-specific expression.ResultsMachine learning identified a 28-protein model that accurately differentiated COVID-19 patients from ICU non-COVID-19 patients (accuracy = 0.89, AUC = 1.00, F1 = 0.89) and healthy controls (accuracy = 0.89, AUC = 1.00, F1 = 0.88). An optimal nine-protein model (PF4V1, NUCB1, CrkL, SerpinD1, Fen1, GATA-4, ProSAAS, PARK7, and NET1) maintained high classification ability. Specific proteins correlated with hemoglobin, coagulation factors, hypertension, and high-flow nasal cannula intervention (P < 0.01). Time-course analysis of the 28 leading proteins demonstrated no significant temporal changes within the COVID-19 cohort. NLP analysis identified multi-system expression of the key proteins, with the digestive and nervous systems being the leading systems.ConclusionsThe plasma proteome of critically ill COVID-19 patients was distinguishable from that of non-COVID-19 sepsis controls and healthy control subjects. The leading 28 proteins and their subset of 9 proteins yielded accurate classification models and are expressed in multiple organ systems. The identified COVID-19 proteomic signature helps elucidate COVID-19 pathophysiology and may guide future COVID-19 treatment development.

Non-cross-reactive epitopes dominate the humoral immune response to COVID-19 vaccination - kinetics of plasma antibodies, plasmablasts and memory B cells.

COVID-19 vaccines are highly effective in inducing protective immunity. While the serum antibody response to COVID-19 vaccination has been studied in depth, our knowledge of the underlying plasmablast and memory B cell (Bmem) responses is still incomplete. Here, we determined the antibody and B cell response to COVID-19 vaccination in a naïve population and contrasted it with the response to a single influenza vaccination in a primed cohort. In addition, we analyzed the antibody and B cell responses against the four endemic human coronaviruses (HCoVs). Measurement of specific plasma IgG antibodies was combined with functional analyses of antibody-secreting plasmablasts and Bmems. SARS-CoV-2- and HCoV-specific IgG antibodies were quantified with an in-house bead-based multiplexed immunoassay. The antibody and B cell responses to COVID-19 vaccination reflected the kinetics of a prime-boost immunization, characterized by a slow and moderate primary response and a faster and stronger secondary response. In contrast, the influenza vaccinees possessed robust immune memory for the vaccine antigens prior to vaccination, and the recall vaccination moderately boosted antibody production and Bmem responses. Antibody levels and Bmem responses waned several months after the 2nd COVID-19 vaccination, but were restored upon the 3rd vaccination. The COVID-19 vaccine-induced antibodies mainly targeted novel, non-cross-reactive S1 epitopes of the viral spike protein, while cross-reactive S2 epitopes were less immunogenic. Booster vaccination not only strongly enhanced neutralizing antibodies against an original SARS-CoV-2 strain, but also induced neutralizing antibodies against the Omicron BA.2 variant. We observed a 100% plasma antibody prevalence against the S1 subunits of HCoVs, which was not affected by vaccination. Overall, by complementing classical serology with a functional evaluation of plasmablasts and memory B cells we provide new insights into the specificity of COVID-19 vaccine-induced antibody and B cell responses.

Baseline characteristics of SARS-CoV-2 vaccine non-responders in a large population-based sample.

Studies indicate that individuals with chronic conditions and specific baseline characteristics may not mount a robust humoral antibody response to SARS-CoV-2 vaccines. In this paper, we used data from the Texas Coronavirus Antibody REsponse Survey (Texas CARES), a longitudinal state-wide seroprevalence program that has enrolled more than 90,000 participants, to evaluate the role of chronic diseases as the potential risk factors of non-response to SARS-CoV-2 vaccines in a large epidemiologic cohort. A participant needed to complete an online survey and a blood draw to test for SARS-CoV-2 circulating plasma antibodies at four-time points spaced at least three months apart. Chronic disease predictors of vaccine non-response are evaluated using logistic regression with non-response as the outcome and each chronic disease + age as the predictors. As of April 24, 2023, 18,240 participants met the inclusion criteria; 0.58% (N = 105) of these are non-responders. Adjusting for age, our results show that participants with self-reported immunocompromised status, kidney disease, cancer, and "other" non-specified comorbidity were 15.43, 5.11, 2.59, and 3.13 times more likely to fail to mount a complete response to a vaccine, respectively. Furthermore, having two or more chronic diseases doubled the prevalence of non-response. Consistent with smaller targeted studies, a large epidemiologic cohort bears the same conclusion and demonstrates immunocompromised, cancer, kidney disease, and the number of diseases are associated with vaccine non-response. This study suggests that those individuals, with chronic diseases with the potential to affect their immune system response, may need increased doses or repeated doses of COVID-19 vaccines to develop a protective antibody level.

First DFT-supported point of care and novel electrochemical biosensing: Determination of yellow fever NS1 antibody in human plasma

In our study, we developed a point of care electrochemical biosensing platform based on the functionalized cysteine-positioned gold electrode to diagnose yellow fever disease from human plasma samples. The developed platform underwent characterization through diverse methods encompassing cyclic voltammetry, electrochemical impedance spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and density-functional theory. The capacitive interaction between yellow fever virus non-structural antigen and antibody gave a cathodic signal at approximately −260 mV, and increased in proportion to the amount of non-structural antibody. The created electrochemical biosensor has an ability to detect 96 ag/mL of the yellow fever non-structural antibody with an extensive analytical range varied from 0.1 fg/mL to 1 μg/mL. The interference effects of various substances that could be found in human plasma, and the performance of the method were examined from the point of recovery and relative standard deviation for human plasma samples; hereby, the results confirmed the unprecedented selectivity and accuracy of the proposed method.

A new perspective on therapies involving B-cell depletion in autoimmune diseases.

It has been rediscovered in the last fifteen years that B-cells play an active role in autoimmune etiology rather than just being spectators. The clinical success of B-cell depletion therapies (BCDTs) has contributed to this. BCDTs, including those that target CD20, CD19, and BAFF, were first developed to eradicate malignant B-cells. These days, they treat autoimmune conditions like multiple sclerosis and systemic lupus erythematosus. Particular surprises have resulted from the use of BCDTs in autoimmune diseases. For example, even in cases where BCDT is used to treat the condition, its effects on antibody-secreting plasma cells and antibody levels are restricted, even though these cells are regarded to play a detrimental pathogenic role in autoimmune diseases. In this Review, we provide an update on our knowledge of the biology of B-cells, examine the outcomes of clinical studies employing BCDT for autoimmune reasons, talk about potential explanations for the drug's mode of action, and make predictions about future approaches to targeting B-cells other than depletion.

Natural Antibodies Produced in Vaccinated Patients and COVID-19 Convalescents Hydrolyze Recombinant RBD and Nucleocapsid (N) Proteins.

Antibodies are protein molecules whose primary function is to recognize antigens. However, recent studies have demonstrated their ability to hydrolyze specific substrates, such as proteins, oligopeptides, and nucleic acids. In 2023, two separate teams of researchers demonstrated the proteolytic activity of natural plasma antibodies from COVID-19 convalescents. These antibodies were found to hydrolyze the S-protein and corresponding oligopeptides. Our study shows that for antibodies with affinity to recombinant structural proteins of the SARS-CoV-2: S-protein, its fragment RBD and N-protein can only hydrolyze the corresponding protein substrates and are not cross-reactive. By using strict criteria, we have confirmed that this proteolytic activity is an intrinsic property of antibodies and is not caused by impurities co-eluting with them. This discovery suggests that natural proteolytic antibodies that hydrolyze proteins of the SARS-CoV-2 virus may have a positive impact on disease pathogenesis. It is also possible for these antibodies to work in combination with other antibodies that bind specific epitopes to enhance the process of virus neutralization.

CCR6+ T helper cells and regulatory T cells in the blood and gastric mucosa during Helicobacter pylori infection.

Helicobacter pylori (H. pylori) can evade the host's immune response and persist for a long time on the gastric mucosa. T helper (Th) cells appear to be involved in the control of H. pylori bacteria but promote mucosal inflammation. In contrast, regulatory T cells (Tregs) may reduce inflammation but promote H. pylori persistence. CC motif chemokine receptor 6 (CCR6) is involved in the migration of various cells into inflamed gastric mucosa. In this study, we examined CCR6+ Th cells and CCR6+ Tregs during H. pylori infection in humans. Isolation of cells from blood and mucosal biopsies, magnetic separation of В cells, CD4+ and CD4+CCR6+CD45RO+ T cells, antigen-specific activation, B cell response in vitro, flow cytometry, determination of CD4+CD25hiFoxP3+ Tregs and various groups of Th cells. CD4+CCR6+ blood lymphocytes from healthy donors included Th cells and Tregs. These CCR6+ Th cells produced proinflammatory cytokines and also stimulated plasma cell maturation and antibody production in vitro. H. pylori gastritis and peptic ulcer disease were associated with an increase in the number of circulate CD4+CCR6+CD45RO+ cells and the percentage of Th1, Th17 and Th1/17 cells in this lymphocyte subgroup. In H. pylori-positive patients, circulating CD4+CCR6+ cells contained a higher proportion of H. pylori-specific cells compared with their CD4+CCR6- counterparts. H. pylori infection strongly increased the content of CD4+ lymphocytes in the inflamed gastric mucosa, with the majority of these CD4+ lymphocytes expressing CCR6. CD4+CCR6+ lymphocytes from H. pylori-infected stomach included Tregs and in vivo activated T cells, some of which produced interferon-γ without ex vivo stimulation. H. pylori infection causes an increase in the number of mature CD4+CCR6+ lymphocytes in the blood, with a pro-inflammatory shift in their composition and enrichment of the gastric mucosa with CD4+CCR6+ lymphocytes, including CCR6+ Th1 cells and Tregs.

Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood.

Matching donor and recipient blood groups based on red blood cell (RBC) surface ABO glycans and antibodies in plasma is crucial to avoid potentially fatal reactions during transfusions. Enzymatic conversion of RBC glycans to the universal group O is an attractive solution to simplify blood logistics and prevent ABO-mismatched transfusions. The gut symbiont Akkermansia muciniphila can degrade mucin O-glycans including ABO epitopes. Here we biochemically evaluated 23 Akkermansia glycosyl hydrolases and identified exoglycosidase combinations which efficiently transformed both A and B antigens and four of their carbohydrate extensions. Enzymatic removal of canonical and extended ABO antigens on RBCs significantly improved compatibility with group O plasmas, compared to conversion of A or B antigens alone. Finally, structural analyses of two B-converting enzymes identified a previously unknown putative carbohydrate-binding module. This study demonstrates the potential utility of mucin-degrading gut bacteria as valuable sources of enzymes for production of universal blood for transfusions.

Amino acid substitution of the membrane-proximal external region alter neutralization sensitivity in a chronic HIV-1 clade B infected patient

The membrane-proximal external region (MPER) represents a highly conserved region of the Human Immunodeficiency Virus (HIV) envelope glycoprotein (env) targeted by several broadly neutralizing antibodies (bnAbs). In this study, we employed single genome amplification to amplify 34 full-length env sequences from the 2005 plasma sample of CBJC504, a chronic HIV-1 clade B infected individual. We identified three amino acid changes (N671S, D674N, and K677R) in the MPER. A longitudinal analysis revealed that the proportion of env sequences with MPER mutations increased from 26.5 % in 2005 to 56.0 % in 2009, and the sequences with the same mutation clustered together. Nine functional pseudoviruses were generated from the 34 env sequences to examine the effect of these mutations on neutralizing activity. Pseudoviruses carrying N674 or R677 mutations demonstrate increased sensitivity to autologous plasma and monoclonal antibodies 2F5, 4E10, and 10E8. Reverse mutations were performed in env including N674, R677, D659, and S671/N677 mutations, to validate the impact of the mutations on neutralizing sensitivity. Neutralization assays indicated that the N671S mutation increased neutralization sensitivity to 2F5 and 10E8. The amino acid R at position 677 increased viral resistance to 10E8, whereas N enhanced viral resistance to 4E10 and 10E8. It has been proposed that critical amino acids in the extra-MPER and the number of potential N-like glycosylation sites (PNGSs) in the V1 loop may have an impact on neutralizing activity. Understanding the mutations and evolution of MPER in chronically infected patients with HIV-1 is crucial for the design and development of vaccines that trigger bnAbs against MPER.

Metabolomic profiling of maternal plasma identifies inverse associations of acetate and urea with anti-SARS-CoV-2 antibody titers following COVID-19 vaccination during pregnancy.

We conducted a comprehensive metabolomic analysis of plasma samples obtained from pregnant women who displayed varying post-vaccination antibody titers after receiving mRNA-1273-SARS-CoV-2 vaccines. The study involved 62 pregnant women, all of whom had been vaccinated after reaching 24weeks of gestation. To quantify post-vaccination plasma antibody titers, we employed binding antibody units (BAU) in accordance with the World Health Organization International Standard. Subsequently, we classified the study participants into three distinct BAU/mL categories: those with high titers (above 2000), medium titers (ranging from 1000 to 2000), and low titers (below 1000). Plasma metabolomic profiling was conducted using 1H nuclear magnetic resonance spectroscopy, and the obtained data were correlated with the categorized antibody titers. Notably, in pregnant women exhibiting elevated anti-SARS-CoV-2 antibody titers, reduced plasma concentrations of acetate and urea were observed. A significant negative correlation between these compounds and antibody titers was also evident. An analysis of metabolomics pathways revealed significant inverse associations between antibody titers and four distinct amino acid metabolic pathways: (1) biosynthesis of phenylalanine, tyrosine, and tryptophan; (2) biosynthesis of valine, leucine, and isoleucine; (3) phenylalanine metabolism; and (4) degradation of valine, leucine, and isoleucine. Additionally, an association between the synthesis and degradation pathways of ketone bodies was evident. In conclusion, we identified different metabolic pathways that underlie the diverse humoral responses triggered by COVID-19 mRNA vaccines during pregnancy. Our data hold significant implications for refining COVID-19 vaccination approaches in expectant mothers. KEY MESSAGES : Anti-SARS-CoV-2 antibody titers decline as the number of days since COVID-19 vaccination increases. Anti-SARS-CoV-2 antibody titers are inversely associated with acetate, a microbial-derived metabolite, and urea. Amino acid metabolism is significantly associated with SARS-CoV-2 antibody titers.

Molecular Epidemiology of Hepatitis E Virus Genotypes in Blood Donors in Peshawar, Khyber Pakhtunkhwa

Background: Hepatitis E virus (HEV), an RNA virus, poses a significant global health threat, affecting 2.3 billion people annually, causing 70,000 deaths, over 50% of acute viral hepatitis cases. In Pakistan, HEV prevalence is high among pregnant women (26%), with a mortality rate of 26 to 30%. Blood transmission is a leading source of sporadic HEV infection.&#x0D; Methodology: The blood specimens were investigated with HEV to detect anti- IgM and IgG antibodies. Anti HEV IgM positive specimens confirmed the incidence of viral RNA by Polymerase chain reactions. The positive cases containing viral RNA were subjected to sequencing of ORF2.&#x0D; Result: A total of 3480 blood specimens were screened serologically by ELISA for the existence of anti HEV IgM and anti-HEV IgG antibodies. Of these 3480 samples, 170 (4.9%) were confirmed positive when screened for HEV antibodies among study population, there was a statistically significant difference observed between males and females (p=0.00001). From 170 positive samples, 60 (1.72 %) were positive for having anti-HEV IgM antibodies in plasma, whereas 110 (3.16 %) were found with anti-HEV IgG antibodies. Among 60 (1.72 %) IgM-positive samples, 18 (0.51 %) were confirmed positive by PCR for the presence of HEV-RNA. Genotype 1 was observed in all 18 HEV RNA-positive samples. &#x0D; Conclusion: The findings of this study underscore the urgency of implementing HEV screening protocols before blood donation. The risk of transmission through blood products is evident, with 4.9% of screened blood specimens exhibiting HEV antibodies. Therefore, the National Blood Transfusion Regulatory Authority must incorporate HEV screening as a routine procedure in Pakistan.

XX sex chromosome complement modulates immune responses to heat-killed Streptococcus pneumoniae immunization in a microbiome-dependent manner.

Differences in male vs. female immune responses are well-documented and have significant clinical implications. While the immunomodulatory effects of sex hormones are well established, the contributions of sex chromosome complement (XX vs. XY) and gut microbiome diversity on immune sexual dimorphisms have only recently become appreciated. Here we investigate the individual and collaborative influences of sex chromosome complements and gut microbiota on humoral immune activation. Male and female Four Core Genotype (FCG) mice were immunized with heat-killed Streptococcus pneumoniae (HKSP). Humoral immune responses were assessed, and X-linked immune-related gene expression was evaluated to explain the identified XX-dependent phenotype. The functional role of Kdm6a, an X-linked epigenetic regulatory gene of interest, was evaluated ex vivo using mitogen stimulation of B cells. Additional influences of the gut microbiome on sex chromosome-dependent B cell activation was also evaluated by antibiotically depleting gut microbiota prior to HKSP immunization. Reconstitution of the depleted microbiome with short-chain fatty acid (SCFA)-producing bacteria tested the impact of SCFAs on XX-dependent immune activation. XX mice exhibited higher HKSP-specific IgM-secreting B cells and plasma cell frequencies than XY mice, regardless of gonadal sex. Although Kdm6a was identified as an X-linked gene overexpressed in XX B cells, inhibition of its enzymatic activity did not affect mitogen-induced plasma cell differentiation or antibody production in a sex chromosome-dependent manner ex vivo. Enhanced humoral responses in XX vs. XY immunized FCG mice were eliminated after microbiome depletion, indicating that the microbiome contributes to the identified XX-dependent immune enhancement. Reconstituting microbiota-depleted mice with select SCFA-producing bacteria enhanced fecal SCFA concentrations and increased humoral responses in XX, but not XY, FCG mice. However, exposure to the SCFA propionate alone did not enhance mitogenic B cell stimulation in ex vivo studies. FCG mice have been used to assess sex hormone and sex chromosome complement influences on various sexually dimorphic traits. The current study indicates that the gut microbiome impacts humoral responses in an XX-dependent manner, suggesting that the collaborative influence of gut bacteria and other sex-specific factors should be considered when interpreting data aimed at delineating the mechanisms that promote sexual dimorphism.

Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans

Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures to antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA vaccination rather than priming Omicron-specific naive B cells. These findings indicate that immune imprinting occurs after repeated Wuhan-Hu-1 spike exposures, but whether it can be overcome remains unclear. To understand the persistence of immune imprinting, we investigated memory and plasma antibody responses after administration of the updated XBB.1.5 COVID-19 mRNA vaccine booster. We showed that the XBB.1.5 booster elicited neutralizing antibody responses against current variants that were dominated by recall of pre-existing memory B cells previously induced by the Wuhan-Hu-1 spike. Therefore, immune imprinting persists after multiple exposures to Omicron spikes through vaccination and infection, including post XBB.1.5 booster vaccination, which will need to be considered to guide future vaccination.

Experiences in the use of multiple doses of convalescent plasma in critically ill patients with COVID-19: An early phase 1 descriptive study.

At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, transfusion of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) emerged as a potential therapeutic strategy to help patients severely afflicted by COVID-19. The efficacy of CCP has been controversial as it depends on many variables pertaining to the plasma donor and the patient with COVID-19, for example, time of convalescence or symptoms onset. This feasibility and descriptive study aimed to assess the safety of multiple doses of CCP in mechanically ventilated, intubated patients with respiratory failure due to COVID-19. A cohort of 30 patients all experiencing severe respiratory failure and undergoing invasive mechanical ventilation in an intensive care unit, received up to five doses of 300-600 mL of CCP on alternate days (0, 2, 4, 6, and 8) until extubation, futility, or death. Nineteen patients received five doses, seven received four, and four received two or three doses. At 28-day follow-up mark, 57% of patients recovered and were sent home, and the long-term mortality rate was 27%. Ten severe adverse events reported in the study were unrelated to CCP transfusion. Independent of the number of transfused doses, most patients had detectable levels of total and neutralizing antibodies in plasma. This study suggests that transfusion of multiple doses of CCP is safe. This strategy may represent a viable option for future studies, given the potential benefit of CCP transfusions during the early stages of infection in unvaccinated populations and in settings where monoclonal antibodies or antivirals are contraindicated or unavailable.

Change in the Frequency of Diabetic Ketoacidosis in Children with Newly Diagnosed Type 1 Diabetes in the Central Anatolia Region of Turkey over the Years Before and After the Coronavirus Disease 2019 Pandemic: A Single-Center Experience.

The number of admissions for severe diabetic ketoacidosis (DKA) in children with newly diagnosed type 1 diabetes (T1D) increased during the coronavirus disease 2019 pandemic. We aimed to investigate whether there has been a change in this situation in recent years. All children with T1D who were diagnosed in our tertiary hospital between 2019 and 2023 were included. Plasma insulin, C-peptide, hemoglobin A1c (HbA1c), and antibodies against thyroid peroxidase, thyroglobulin, insulin, islet cell, glutamic acid decarboxylase, tissue transglutaminase IgA, and endomysium IgA were measured. The frequency of moderate-severe acidosis at admission, which increased after pandemic period compared to the pre-pandemic period, returns to its previous levels over time but still shows a statistical difference compared to the pre-pandemic period (P = .012). Age, blood gas pH and HCO3 level, C-peptide, HbA1c, and length of stay of children at the time of admission were compared year by year (years 2019-2023). No statistical differences were observed (P = .509, P = .181, P = .069, P = .469, P = .346, P = .946), respectively. A significant difference was observed in venous glucose (P .001) and insulin (P = .001) according to years. Also, no significant difference was found about the degree of acidosis according to age (P = .334). Although the frequency of DKA in children with newly-diagnosed T1D increased in the first years of the pandemic, it has been decreasing over t.

B cell-reactive triad of B cells, follicular helper and regulatory T cells at homeostasis

Autoreactive B cells are silenced through receptor editing, clonal deletion and anergy induction. Additional autoreactive B cells are ignorant because of physical segregation from their cognate autoantigen. Unexpectedly, we find that follicular B cell-derived autoantigen, including cell surface molecules such as FcγRIIB, is a class of homeostatic autoantigen that can induce spontaneous germinal centers (GCs) and B cell-reactive autoantibodies in non-autoimmune animals with intact T and B cell repertoires. These B cell-reactive B cells form GCs in a manner dependent on spontaneous follicular helper T (TFH) cells, which preferentially recognize B cell-derived autoantigen, and in a manner constrained by spontaneous follicular regulatory T (TFR) cells, which also carry specificities for B cell-derived autoantigen. B cell-reactive GC cells are continuously generated and, following immunization or infection, become intermixed with foreign antigen-induced GCs. Production of plasma cells and antibodies derived from B cell-reactive GC cells are markedly enhanced by viral infection, potentially increasing the chance for autoimmunity. Consequently, immune homeostasis in healthy animals not only involves classical tolerance of silencing and ignoring autoreactive B cells but also entails a reactive equilibrium attained by a spontaneous B cell-reactive triad of B cells, TFH cells and TFR cells.

A Descriptive, Retrospective Analysis of COVID-19 Passive Antibody Therapy and Its Effects on Morbidity and Mortality in Patients Receiving B-Cell-Depleting Therapies.

Patients receiving B-cell-depleting therapies (BCDT) are at an increased risk for severe COVID-19. Passive antibody therapy (PAT), including COVID-19 convalescent plasma (CCP) and monoclonal antibodies (mAb), may be an effective treatment in this population. Real-world data on PAT effectiveness are limited. To evaluate response to PAT measured through 90-day all-cause morbidity and mortality, we performed a retrospective review of patients who contracted COVID-19 within a year from the last BCDT. From 64 included patients, the majority were Caucasians (95%), female (56%), vaccinated (67%), treated outpatients (64%), with multiple comorbidities. Examined BCDT were rituximab (55%), obinutuzumab (33%), ocrelizumab (11%) and ofatumumab (1%), used for underlying hematological malignancy (HEM) (40%), multiple sclerosis (34%), and rheumatoid arthritis (16%). Of seven deceased patients, three died from COVID-19. All three were elderly males with multiple comorbidities, treated inpatient for severe COVID-19. Four of 41 patients treated as outpatients were hospitalized for non-COVID-19-related reasons. All deceased and hospitalized patients had an underlying HEM. All but one were on rituximab. PAT may be an effective treatment for patients receiving BCDT, especially if given early for non-severe disease. Patients with underlying HEM may be at increased risk for severe disease compared with others receiving the same BCDT.