Elevated Titers Research Articles

Association between Elevated TGA-IgA Titers and Older Age at Diagnosis with Absence of HBV Seroconversion in Celiac Children.

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy.

In from the cold: M-protein light chain glycosylation is positively associated with cold agglutinin titer levels.

Primary cold agglutinin disease (CAD) is a monoclonal antibody (M-protein) and complement-mediated chronic hemolytic disease process. Antibody glycosylation can play a role in both antibody half-life and complement fixation. Recently, M-protein light chain (LC) glycosylation has been shown to be associated with AL amyloidosis. We hypothesized that M-protein LC glycosylation is also associated with cold agglutinin (CA) titers and CA-mediated hemolysis. A cross-sectional study of patients undergoing CA titer evaluation underwent mass spectrometric analysis for M-proteins and M-protein LC glycosylation. A subset of serum samples also underwent evaluation for the ability to trigger cold hemolysis in vitro. M-protein and M-protein LC glycosylation rates were compared across CA titer groups, clinical diagnosis, direct antiglobulin testing (DAT) results, and cold in vitro hemolysis rates. Both M-protein and M-protein LC glycosylation rates significantly differed across CA titer groups with the highest rates in those with elevated CA titers. M-protein LC glycosylation occurred almost exclusively on IgM kappa M-proteins and was significantly associated with positive DAT results and a clinical diagnosis of CAD. Cold in vitro hemolysis was demonstrated in two patients who both had a CA titer of more than 512 but there was no significant association with CA titer group or M-protein LC glycosylation status. M-protein LC glycosylation is significantly associated with higher CA titer levels. Given the role that antibody glycosylation can play in antibody half-life and complement fixation, further studies are needed to clarify the effects of LC glycosylation within the context of CAD.

Factors associated with anti-SARS-CoV-2 IgG antibody production in patients convalescing from COVID-19

IntroductionAmong patients with coronavirus disease 2019 (COVID-19), the factors that affect anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody production remain unclear. This study aimed to identify such factors among patients convalescing from COVID-19. MethodsThis study comprised patients who had been diagnosed with COVID-19 between January 1 and June 30, 2020 and gave consent for anti-SARS-CoV-2 spike protein antibody measurement using enzyme-linked immunosorbent assay during their acute and/or convalescent phases. Factors related to elevated antibody titers and the relationship between the days from disease onset and the development of antibody titers were assessed. ResultsA total of 84 participants enrolled in the study. Nineteen participants had antibody titers measured during the convalescent phase only, and 65 participants had antibody titers measured during the acute and convalescent phases. The antibody titers peaked in weeks 5 and 6. The stepwise multivariate log-normal analysis revealed that male sex (P = 0.04), diabetes mellitus (P = 0.03), and high C-reactive protein levels during the disease course (P < 0.001) were associated with elevated IgG antibodies. Glucocorticoid use was not associated with antibody titers. ConclusionThe study found that high values of maximum CRP levels during the acute phase, male sex, and diabetes mellitus were associated with elevated antibody titers. Antibody titers tended to be highest in the first 5 or 6 weeks after the onset of symptoms.

Isolated neurobrucellosis-characteristic clinical and laboratory features.

To report various neurological syndromes, CSF findings, imaging and diagnostic methods used in neurobrucellosis patients admitted in our Neurology department over a period of 6years. Case records of patients admitted to our department from August 2014 to May 2020 were searched for neurobrucellosis and data were obtained. A total of 19 patients were diagnosed as neurobrucellosis over a period of 6years. Ten patients had chronic meningitis, five had VIII nerve involvement, one had optic neuritis, two had acute meningitis, one had subacute meningitis, four had myelopathy, five had polyradiculitis and two had spondylodiscitis. CSF was abnormal in 17 patients. Neutrophilic pleocytosis was seen in 12 patients who included nine patients with chronic symptomatology.Brain imaging was abnormal in three chronic meningitis patients. One had diffuse meningeal enhancement, another had hydrocephalus while the third patient had meningeal enhancement with basal exudates and contrast enhancement of bilateral VIII nerve. One of the patients of acute meningitis had hydrocephalus while the other one had bilateral T2/FLAIR hyperintensities with enhancement of meninges and leptomeningeal vessels. Elevated antibody titers only in serum was seen in six patients while elevated antibody titers only in CSF was seen in seven patients. Four patients had elevated antibody titers in both serum and CSF. CSF culture was positive in three patients. Neurobrucellosis is a rare clinical complication of brucellosis but may pose a problem in diagnosis as it can mimic tuberculosis. Involvement of VIII nerve and neurophilic pleocytosis in CSF despite chronic symptomatology can be diagnostic clues favoring neurobrucellosis.

Savremeni kritički pristup dijagnozi akutnih virusnih miokardita i inflamatornih kardiomiopatija u kliničkoj praksi - fokus na uloge ehokardiografije i antivirusnih antitela

SIGNIFICANCE OF THE PROBLEM: The diagnosis of acute viral myocarditis is one of the diagnoses most difficult to make in cardiology and medicine in general. Echocardiography and cardiomagnetic resonance play a crucial role in the clinical diagnosis and the serum titer of antiviral antibodies to cardiotropic viruses is still unjustifiably used for the diagnosis of myocarditis in everyday practice. RESEARCH OBJECTIVES: To analyze the frequency and significance of echocardiographic parameters in the diagnosis of clinically suspected acute viral myocarditis, to determine the role of antiviral antibody titer (AVA) dynamics for the diagnosis of myocarditis and to compare viral serology and echocardiographic function versus echocardiographic function. METHODOLOGY: A retrograde transverse study was performed in the ten-year period from 2006. to 2015, where 126 consecutive patients from the database of the Office of Internal medicine ''Dr. Bastać'' were analyzed, with a working diagnosis of clinically suspected viral myocarditis. They were clinically, ECG, echocardiographically and serologically monitored for 4 to 8 weeks due to the dynamics of AVA titer. The examined group (A) was divided into subgroups: A1 with elevated AVA class IgM titer in 43 (32%) subjects and subgroup A2 without elevated IgM titer in 83 (68%) patients. The control group of healthy (B) of 103 subjects was comparable.Statistical processing was done in the EXCELL database via descriptive statistics, Student's-T test and Chi2 test. RESULTS: 126 patients had clinically suspected myocarditis (≥2 ESC criteria). Diastolic left ventricular dysfunction in 39/126 (31%) patients was the dominant echocardiographic criterion for clinically suspected myocarditis. Reduced ejection fraction (EF &lt;50%) was measured at 19/126 (15%), followed by left ventricular dilatation. Regional systolic dysfunction was found in 21/126 (17%) and changes in myocardial texture in 17 (13%) subjects. The clinical probability of viral etiology was diagnostically supported by elevated titer of IgM antibodies in 43 (32%) subjects (subgroup A1) where IgM antibodies to Parvo B 19 virus predominate in 36/43 patients (84%). Most were without elevated titer of IgM antibodysubgroup A2 83 (68%). Clear dynamics of IgM antibody titer was observed in 23 persons, a decrease in IgM titer with an increase in IgG titer (seroconversion) in 13 patients. Determination of anti-heart autoantibodies (AHA) was done in 17 severe cases, of which 9 had positive AHA. A comparison of subgroups A1 and A2 did not reveal a statistically significant difference in echocardiographic parameters. The whole group A of clinically suspected myocarditis compared to control group B has statistically highly significantly lower parameters of global systolic (EF=8,7±4,6 vs. 63±7,9; p&lt;0,001), longitudinal systolic (S'=6,9±1,3 vs. 9,9±2,1) and diastolic function (E/e'11,9±4,8 vs. 8,7±4,6; p&lt;0,001), and a highly statistically significant increase in left ventricular telediastolic dimension, myocardial mass index, and left atrial size. CONCLUSION: The diagnosis of acute viral myocarditis in clinical practice is made on the basis of the clinical picture, ECG and echocardiography that indicate myocarditis with the exclusion of cardiac comorbidities, based on the ESC criteria for suspected clinical myocarditis. The whole group A had highly statistically significantly lower parameters of systolic and diastolic function compared to control group B. Normal ECG and echocardiography cannot serve to exclude the diagnosis of myocarditis. Comparison of subgroups A1 and A2 did not reveal a statistically significant difference in echocardiographic parameters.

Spatial Distribution of Serologically Reactive Sheep to Leptospira spp. in the Northeast Region of Brazil

Background: Considering the importance of leptospirosis in sheep farming and public health and the significance of identifying which serogroups circulate in sheep within each region, the objective of this study was to determine the seroprevalence and spatial distribution of the most frequent serogroups causing infection by Leptospira sp. in ovine herds in the Northeast region of Brazil.Materials, Methods &amp; Results: Blood samples were collected from 4197 sheep from 229 herds in 7 Northeastern States. Sera were analyzed via microscopic agglutination test (MAT). The frequency of seroreactive sheep for Leptospira sp. was 14.06%. The states of Alagoas, Ceará, Paraíba, Piauí, Rio Grande do Norte, and Sergipe, located in the Caatinga biome, had the highest frequencies of serologically reactive sheep, and Maranhão, in the Cerrado biome, had the lowest frequency. The most frequent serogroups were Autumnalis (19.49%), Australis (15.76%) and Serjoe (14.41%). In the states of Ceará, Paraíba, Rio Grande do Norte, and Sergipe, 100% of their municipalities had at least one seroreactive animal. The highest frequencies of seropositive animals were found in the municipalities of União (50%), Passagem (49.06%), Canindé (48.89%), Igaci (28.95%), Gararu (31.2%), Pirapemas (17.5%), and Angicos (16%) located in the states of Piauí, Paraíba, Ceará, Alagoas, Sergipe, Maranhão and Rio Grande do Norte, respectively.Discussion: The animal-level prevalence (14.06%) obtained in the present study is significant, especially considering the rustic nature of the species and the adverse conditions of the region for the infectious agent. In semi-arid conditions, it has been suggested that perhaps sheep do not seroconvert detectable titers on MAT with a cut-off point of 1:100. It is important to highlight that theovine population in the Northeast region of Brazil is composed of mixed animals, which have been considered more resistant to infection by Leptospira spp. Also, environmental factors hostile to the survival of the infectious agent in the studied region should be taken into consideration, since they may have influenced the seropositive animal-level prevalence. A noteworthy variation was observed in agglutinin titers, which ranged from 100 to 1,600, where 80.2% of the positive samples had titers ≤ 200. It is important to highlight that more elevated titers (≥ 400) were obtained in all seven states, which may suggest an acute infection caused by a non-adapted serovar, indicating that preventive and control measures focused on possible infection sources for sheep should be adopted. Although some states showed the same serogroups as the most frequent, a variety of serogroups was observed in municipalities, which may indicate different sources of infection, whether interspecies, intraspecies, or via alternative routes of transmission in semi-arid conditions, such as venereal. This indicates that even though sheep are more resistant to infection, they become exposed due to the environment or management conditions. As such, identification, isolation, and treatment of the affected animals are alternative measures recommended for prevention and control of leptospirosis in sheep in the semi-arid region. It is evident that despite the lack of rain observed in the last decade in the Northeast region of Brazil, which prevented the formation of favorable environments for the presence of Leptospira, the infectious agent remains among the sheep, as well as other production and wild animals in the region. Some factors may be contributing to this scenario, such as the fact that sheep farming in the region is characterized mainly by subsistence systems, where veterinary assistance and adequate sanitary management are absent, thus increasing the possibility of contact with Leptospira.Keywords: small ruminants, semi-arid, zoonosis.

Silkworm recombinant bovine zona pellucida protein 4 (bZP4) as a potential female immunocontraceptive antigen; impaired sperm-oocyte interaction and ovarian dysfunction.

Porcine zona pellucida proteins (ZPs) have been utilized as female immunocontraceptive antigens. The purpose of this study was to explore the potential use of silkworm recombinant bovine ZP4 as an alternative. When the protein was injected with monophosphoryl lipid A (MPL) – an immuno-stimulative agent – into two female goats, marked elevation of the anti-ZP4 titer was detected. Application of the purified specific IgG to a porcine in vitro fertilization system reduced the sperm penetration rate. In one goat, the cyclic profile of serum progesterone disappeared as the anti-ZP4 titer increased. Histological examination of the ovaries revealed degeneration of antral follicles with sparse infiltration of inflammatory cells in the theca, indicating that autoimmune oophoritis had been induced. Together, the present results suggest that recombinant ZP4 disturbs fertilization and exerts a pathogenic effect on follicle development in goats, thus indicating its potential as a female immunocontraceptive antigen.

What is the True Etiology of “Recurrent Shingles”?

Purpose: To determine the true etiology of cases of putative recurrent shingles referred to a dermatology clinic. Methods: A prospective cohort study of patients aged 15-87 years with reported recurrent herpes zoster was conducted. Vesicular fluid and serology for herpes simplex 1, 2, and varicella zoster virus immunoglobulins were obtained from patients presenting with vesicles. Biopsies were obtained from patients with ambiguous presentations. Results: 44 patients (56%) had evidence of herpes simplex virus infection. 32% of patients had positive herpes simplex virus cultures or polymerase chain reaction sequencing, and 24% additional patients were diagnosed with presumptive simplex infection based on elevated antibody titers. 44% of patients had a diagnosis other than zoster or simplex. One individual had a positive viral culture for varicella zoster virus. 99% of patients who presented with suspected recurrent herpes zoster had no definitive evidence of varicella zoster virus reactivation. Conclusions: The most common diagnosis was herpes simplex infection. Our results suggest that true recurrent shingles in immunocompetent patients is rare.

Subacute Sclerosing Panencephalitis (SSPE) in Toddlers and Young Children: A Case Series

SSPE is a neurodegenerative disorder caused by persistent defective or mutant measles virus. The disease has a gradual progressive course leading to death within 1-3 yrs or even early. SSPE is a disease of childhood and early adolescence. The classic age at presentation is 8-11 years and usually occurs after a latent period of average 6 years. Here we report 3 cases of SSPE in toddlers. Diagnosis was made on the basis of clinical presentation, EEG pattern and elevated CSF anti measles antibody titer as described in Dykan criteria for diagnosis of SSPE. Clinical presentation was very early with a relatively shorter latency and fatal progression. Two patients had past history of measles and all patients were immunized against measles. One patient died within 4 months of disease expression and 2 patients went into vegetative state within 3 months of disease onset.&#x0D; Bangladesh J Child Health 2020; VOL 44 (2) :114-117

Kidney re-transplantation in a child across the barrier of persisting angiotensin II type I receptor antibodies

BackgroundApproximately 20% of antibody-mediated rejection (ABMR) episodes in the absence of donor-specific antibodies against human leucocyte antigens (HLA-DSA) in pediatric and adult kidney transplant recipients are associated with, and presumably caused by, antibodies against the angiotensin type 1 receptor (AT1R-Ab). While the role of AT1R-Ab for ABMR and graft failure is increasingly recognized, there is little information available on the management of these patients for re-transplantation over the barrier of persisting AT1R-Ab.CaseWe report on a male patient with kidney failure in infancy due to obstructive uropathy who had lost his first kidney transplant due to AT1R-Ab-mediated chronic ABMR. Because this antibody persisted during 4 years of hemodialysis, for the 2nd kidney transplantation (living-related transplantation from his mother), he underwent a desensitization regimen consisting of 15 plasmapheresis sessions, infusions of intravenous immunoglobulin G and thymoglobulin, as well as pharmacological blockade of the Angiotensin II (AT II) pathway by candesartan. This intense desensitization regimen transiently decreased elevated AT1R-Ab titers, resulting in stable short-term kidney allograft function. The subsequent clinical course, however, was complicated by acute cellular rejection and chronic ABMR due to persistent AT1R-Ab and de novo HLA-DSA, which shortened allograft survival to a period of only 4 years.ConclusionThis case highlights the difficulty of persistently decreasing elevated AT1R-Ab titers by a desensitization regimen for re-transplantation and the detrimental effect of the interplay between AT1R-Ab and HLA-DSA on kidney transplant survival.

Optimized GAPDH-truncated immunogen of Streptococcus equi elicits an enhanced immune response and provides effective protection in a mouse model

Strangles is an acute and frequently diagnosed infectious disease caused by Streptococcus equi subsp. equi. Infection with this pathogen can cause grave losses to the equine industry. The present work investigates glyceraldehyde-3-phosphate dehydrogenase (GAPDH), an important surface-localized virulence factor of S. equi, to determine whether it could be developed into an efficacious and suitable subunit vaccine against strangles. Two different recombinant fragments of S. equi GAPDH, namely, GAPDH-L and GAPDH-S, were constructed and expressed. Further, the antigenicity and immunogenicity of these two recombinant proteins were compared and evaluated in a mouse model. Our results revealed that immune responses were efficiently induced by the proteins in immunized mice. Remarkably, higher survival rates and significantly lower bacterial loads in the lung, liver, kidney, and spleen were observed in the GAPDH-S group compared with the GAPDH-L group after challenge with S. equi. High levels of specific antibodies, elevated antibody titers, and increased proportions of CD8 + T cells further indicated that GAPDH-S elicited better humoral and cellular immune responses than GAPDH-L. Furthermore, the induction of TCR, TLR-2, TLR-3, and TLR-4 significantly increased in the GAPDH-S group compared with those in the GAPDH-L and negative control groups. In summary, our results indicate that the optimized recombinant protein GAPDH-S is a promising candidate construct that may be further developed into a multivalent subunit vaccine for strangles.

B-Cell-Specific Myd88 L252P Expression Causes a Premalignant Gammopathy Resembling IgM MGUS.

A highly recurrent somatic L265P mutation in the TIR domain of the signaling adapter MYD88 constitutively activates NF-κB. It occurs in nearly all human patients with Waldenström’s macroglobulinemia (WM), a B cell malignancy caused by IgM-expressing cells. Here, we introduced an inducible leucine to proline point mutation into the mouse Myd88 locus, at the orthologous position L252P. When the mutation was introduced early during B cell development, B cells developed normally. However, IgM-expressing plasma cells accumulated with age in spleen and bone, leading to more than 20-fold elevated serum IgM titers. When introduced into germinal center B cells in the context of an immunization, the Myd88L252P mutation caused prolonged persistence of antigen-specific serum IgM and elevated numbers of antigen-specific IgM plasma cells. Myd88L252P-expressing B cells switched normally, but plasma cells expressing other immunoglobulin isotypes did not increase in numbers, implying that IgM expression may be required for the observed cellular expansion. In order to test whether the Myd88L252P mutation can cause clonal expansions, we introduced it into a small fraction of CD19-positive B cells. In this scenario, five out of five mice developed monoclonal IgM serum paraproteins accompanied by an expansion of clonally related plasma cells that expressed mostly hypermutated VDJ regions. Taken together, our data suggest that the Myd88L252P mutation is sufficient to promote aberrant survival and expansion of IgM-expressing plasma cells which in turn can cause IgM monoclonal gammopathy of undetermined significance (MGUS), the premalignant condition that precedes WM.

A commentary revisiting the viral hypothesis of schizophrenia: Onset of a schizophreniform disorder subsequent to SARS CoV-2 infection

The viral hypothesis for schizophrenia has persisted for decades, initially supported by observed increases in psychoses subsequent to the influenza pandemic of the early twentieth century, and then later by evidence of elevated viral antibody titres particularly in schizophrenia patient populations. Several research studies have also focused on maternal infections during the second trimester of pregnancy and their long-term effects on fetal brain development, ultimately leading to schizophrenia. No specific virus has been implicated although a handful have received increasing attention. The current pandemic spreading the SARS CoV-2 corona virus world-wide is now showing anecdotal evidence of psychoses newly developing post viral exposure, implicating neuronal inflammation in crucial areas of the brain that could initiate psychotic symptoms. Time will tell if epidemiological data will, similar to the 1918 influenza pandemic, show that schizophrenia spectrum disorders increase after serious viral infections.

Elevated TPOAb is a Strong Predictor of Autoimmune Development in Patients of Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease: A Case-Control Study.

ObjectiveThe aim of this study was to assess the prevalence of thyroid autoimmunity in T2DM with NAFLD, furthermore explore the relationship between elevated TPOAb titer and the severity of NAFLD.MethodsA total of 400 patients with T2DM were divided into two groups according to NAFLD. Thyroid function and other metabolic indicators were measured.ResultsThere were more TPOAb-positive patients in both groups, and the prevalence of TPOAb positive was significantly different in two groups (17% vs 6.9%, p< 0.01). FT4 was significantly lower in patients with T2DM with NAFLD (median FT4 0.89 vs 1.08, p < 0.001), while TSH was increased (median TSH 2.85 vs 2.28, p < 0.05). In patients with T2DM with NAFLD, the proportion of women in the thyroid autoimmune-positive group was significantly higher than the negative (71.1% vs 46%, p < 0.01). Similarly, thyroid autoimmune-positive T2DM and NAFLD patients had lower FT4 levels (median FT4 0.59 vs 0.92, p < 0.001), higher TSH levels (median TSH 3.65 vs 2.67, p < 0.001), and much higher TPOAb/TGAb (median TPOAb/TGAb 6.8 vs 1.46, p < 0.001). The increase of TPOAb was significantly correlated with the severity of fatty liver. HbA1c, TC, TG, TSH, TPOAb/TGAb and severity of fatty liver were risk factors of thyroid autoimmunity.ConclusionAutoimmune thyroid disease is more common in patients with T2DM complicated with NAFLD. Elevated TPOAb titer is closely related to fatty liver, suggesting that elevated TPOAb titer is a predictor of autoimmune development in T2DM with NAFLD.

Serum IgG titers against periodontal pathogens are associated with cerebral hemorrhage growth and 3-month outcome.

To assess the influence of periodontal disease on cerebral hemorrhage and its clinical course, we examined the association of the serum IgG titer of periodontal pathogens with hemorrhage growth and 3-month outcome. We consecutively enrolled 115 patients with acute cerebral hemorrhage (44 females, aged 71.3 ± 13.1 years) and used ELISA to evaluate the serum IgG titers of 9 periodontal pathogens: Porphyromonas gingivalis, Aggregatibacter (A.) actinomycetemcomitans, Prevotella intermedia, Prevotella nigrescens, Fusobacterium (F.) nucleatum, Treponema denticola, Tannerella forsythensis, Campylobacter rectus, and Eikenella corrodens. Significant hematoma growth was defined as an increase in the volume of >33% or an absolute increase in the volume of >12.5 mL. A poor outcome was defined as a 3 or higher on the modified Rankin Scale. We observed hemorrhage growth in 13 patients (11.3%). Multivariate analysis revealed that increased IgG titers of A. actinomycetemcomitans independently predicted the elevated hemorrhage growth (odds ratio 5.26, 95% confidence interval 1.52-18.25, p = 0.01). Notably, augmented IgG titers of F. nucleatum but not A. actinomycetemcomitans led to a poorer 3-month outcome (odds ratio 7.86, 95% confidence interval 1.08-57.08, p = 0.04). Thus, we demonstrate that elevated serum IgG titers of A. actinomycetemcomitans are an independent factor for predicting cerebral hemorrhage growth and that high serum IgG titers of F. nucleatum may predict a poor outcome in patients with this disease. Together, these novel data reveal how systemic periodontal pathogens may affect stroke patients, and, should, therefore, be taken into consideration in the management and treatment of these individuals.

SLy2-deficiency promotes B-1 cell immunity and triggers enhanced production of IgM and IgG2 antibodies against pneumococcal vaccine.

BackgroundDespite the benefits of existing vaccines, Streptococcus pneumoniae is still responsible for the greatest proportion of respiratory tract infections around the globe, thereby substantially contributing to morbidity and mortality in humans. B‐1 cells are key players of bacterial clearance during pneumococcal infection and even provide long‐lasting immunity towards S. pneumoniae. Previous reports strongly suggest an essential role of the immunoinhibitory adapter Src homology domain 3 lymphocyte protein 2 (SLy2) for B‐1 cell‐mediated antibody production. The objective of this study is to evaluate S. pneumoniae‐directed B cell responses in the context of SLy2 deficiency.MethodsB‐1 cell populations were analyzed via flow cytometry before and after pneumococcal immunization of SLy2‐deficient and wild‐type control mice. Global and vaccine‐specific immunoglobulin M (IgM) and IgG antibody titers were assessed by enzyme‐linked immunosorbent assay. To investigate survival rates during acute pneumococcal lung infection, mice were intranasally challenged with S. pneumoniae (serotype 3). Complementary isolated splenic B cells were stimulated in vitro and their proliferative response was assessed by fluorescent staining. In vitro antibody secretion was quantified by LEGENDplex.ResultsWe demonstrate increased frequencies of B‐1 cells and elevated titers of preantigenic IgM in SLy2‐deficient mice. In addition, these mice produce significantly more amounts of IgM and IgG2 upon pneumococcal vaccination. Knocking out SLy2 did not induce survival advantages in our murine model of acute pneumonia, indicating the presence of compensatory mechanisms.ConclusionOur results reveal reinforced specific antibody responses towards pneumococcal polysaccharides and enhanced IgG2 secretion as a consequence of SLy2 deficiency, which could be relevant to the development of more efficient vaccines.

Outbreak of Tularemia in a Group of Hunters in Germany in 2018-Kinetics of Antibody and Cytokine Responses.

In November 2018, an outbreak of tularemia occurred among hare hunters in Bavaria, Germany. At least one infected hare was confirmed as the source of infection. A number of hunting dogs showed elevated antibody titers to Francisella tularensis, but the absence of titer increases in subsequent samples did not point to acute infections in dogs. Altogether, 12 persons associated with this hare hunt could be diagnosed with acute tularemia by detection of specific antibodies. In nine patients, the antibody and cytokine responses could be monitored over time. Eight out of these nine patients had developed detectable antibodies three weeks after exposure; in one individual the antibody response was delayed. All patients showed an increase in various cytokines and chemokines with a peak for most mediators in the first week after exposure. Cytokine levels showed individual variations, with high and low responders. The kinetics of seroconversion has implications on serological diagnoses of tularemia.

Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity

We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5–7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5–7 months after SARS-CoV-2 infection.

Assessment of Immunostimulating effect of Carica papaya-based Immunostimulatory Complexes Against Streptococcus pneumoniae Infections

Objectives: Streptococcus pneumoniae infection is a bacterial infection responsible for one-fifth of child mortality in Africa. The aim of this study was to formulate and evaluate Carica papaya-based Immunostimulatory complexes against Streptococcus pneumoniae infections. Methods: Leaves of the plant were harvested, air-dried, pulverized and the saponin content extracted using distilled water and but anole in a Soxhlet’s apparatus. The formulation of Immunostimulatory complexes was prepared using the ethanol injection method. Acute toxicity test and Immunological assays, namely: neutrophil adhesion, carbon clearance, hem agglutinating antibody titer were conducted using healthy laboratory mice. The results were compared to standard drug (levamisole). Results: The aqueous extract and butanol fraction yielded 7.45% and 0.38% saponin. At 5000mg/ kg body weight of administered immunostimulatory complexes, no death or behavioral changes were recorded. Neutrophil adhesion showed no significant increase (20.82±4.34) as against the levamisole (20.74±3.31). The increased phagocytic index (0.089± 0.017) showed better stimulation of reticuloendothelial system when compared to both controls (distilled water = 0.032 ± 0.001; levamisole = 0.071 ± 0.001).The lower Hemagglutination antibody titre value indicates the potency of the formulated ISCOM to elicit an immune response. The ISCOM dose (250 mg/kg body weight) significantly elevated hemagglutination antibody titre (7.81±1.60). Conclusion: It can be inferred from this study that Carica papaya leaves has immunomodulatory capacity and has significant saponin yield which could potentially serve as a component of Immunostimulatory complexes formulation. Carica papaya-based Immunostimulatory complexes exhibit improved immunogenicity against Streptococcus pneumoniae infections.

Chilblain-like lesions and COVID-19 infection: A prospective observational study at Spain's ground zero

Chilblain-like lesions and COVID-19 infection: A prospective observational study at Spain's ground zero