Immunological Monitoring Research Articles

Association of CD19+-Targeted Chimeric Antigen Receptor (CAR) T-cell Therapy with Hypogammaglobulinemia, Infection and Mortality

BackgroundCD19-targeted chimeric antigen receptor T-cell therapy (CAR-T therapy) has revolutionized the treatment of hematologic malignancies. As these cells target CD19+ receptors on B-cells, there is the potential for B-cell aplasia and hypogammaglobulinemia. Data on the degree and clinical significance of hypogammaglobulinemia are sparse. ObjectiveTo evaluate hypogammaglobulinemia after CD19-targeted CAR-T therapy and risk factors for hypogammaglobulinemia, infections, and mortality. MethodsWe performed a retrospective evaluation of 579 patients receiving CD19-directed CAR-T therapy and evaluated demographics, hypogammaglobulinemia (immunoglobulin G [IgG]≤600mg/dL), infections pre- and post-CAR-T therapy, and risk factors for hypogammaglobulinemia, infection, hospitalizations, and mortality. ResultsPatients had a mean age of 64 years and 64% were male. Prior to CAR-T therapy, 60% of patients had hypogammaglobulinemia, which increased to 91% post-CAR-T therapy. Mean IgG levels decreased from pre- to post-CAR-T therapy (587 to 362 mg/dL; p<0.0001). 37% of patients developed a serious infection post-CAR-T therapy. Hypogammaglobulinemia pre-CAR-T therapy was associated with worsening hypogammaglobulinemia post-CAR-T therapy. Hypogammaglobulinemia post-CAR-T therapy was associated with an increased risk of serious infection post-CAR-T therapy (IRR=2.7; 95% CI=1.5-5.2; p=0.002). Risk factors for mortality included mild hypogammaglobulinemia (400mg/dL<IgG≤600mg/dL), infections ≤100 days post-CAR-T therapy, and hospitalizations for infections. Immunoglobulin replacement was associated with a decreased risk of mortality. ConclusionsWe identified ∼90% of patients with hypogammaglobulinemia after CAR-T therapy. Hypogammaglobulinemia pre-CAR-T therapy was strongly predictive of worsening hypogammaglobulinemia post-CAR-T therapy, which was associated with an increased risk of serious infection and mortality post-CAR-T therapy. Increased immunological monitoring is needed to identify high-risk patients who may benefit from interventions to decrease morbidity and mortality.

Survey of Post-Prophylaxis Delayed-Onset Cytomegalovirus Management Strategies Among Transplant Providers.

Preventive strategies for cytomegalovirus (CMV) in the posttransplant period have changed the pattern of CMV infections, now more commonly manifesting as late-onset occurrences known as post-prophylaxis delayed-onset CMV disease (PPDOC). We conducted a survey to investigate provider practices in managing PPDOC. A web-based provider survey on the management of PPDOC was developed using Research Electronic Data Capture (REDCap). It was distributed to the online forums of the American Society of Transplantation communities of practice (COP) for Infectious Diseases (IDCOP), Kidney and Pancreas (KPCOP), Liver and Intestinal (LICOP), and Thoracic and Critical Care (TCCOP). The survey was posted twice within a span of a month. Fifty-six respondents, comprising 50 (89%) transplant physicians and 6 (11%) transplant pharmacists, from 46 distinct transplant centers, completed the survey. Universal antiviral prophylaxis (UAP) was the predominant preventive approach for both high-risk (85%) and moderate-risk (85%) transplant recipients. Out of 56, 51 respondents completed the questions regarding management of PPDOC. Regular surveillance with nucleic acid amplification tests (NAAT) (88%) was the most commonly used approach in high-risk recipients, while symptom monitoring (73%) was the most common strategy in moderate-risk recipients. Immunologic monitoring was used only by a few respondents who found it moderately useful in high-risk recipients. Management of PPDOC was highly variable among providers and strategies differed based on patient risk profile. These findings could help shape future studies and guidelines to harmonize CMV management.

The role of immuno-mediated dysregulation in the progression of allergic pathology in military personnel under occupational stress

In order to identify clinical and immunological predictors of the progression of allergopathology in military personnel participating in special operations under conditions of professional stress, 43 military personnel participating in special operations divided into two groups were examined. Group 1 consisted of officers with allergopathology or who first debuted symptoms of allergic diseases during or within 6 months after participating in special operations (n = 13, average age 36.4±4.5 years). Group 2 included officers participating in special operations who did not have symptoms of allergic diseases (n = 13, average age 36.4±4.5 years). The analysis of complaints and medical documentation were carried out. Clinical and laboratory examination was performed without exacerbation of somatic pathology. The immune status was assessed by the expression of CD3+, CD4+, CD8+, CD16+, CD19+, HLA-DR+, intracellular FoxP3 content in CD4+CD25+T cells, granzyme B in CD3-CD16+ and CD3+CD8+ lymphocytes using appropriate monoclonal antibodies (Beckman Coulter) and taking into account the results on the cytofluorometer “FC 500”. Immunological monitoring was performed before participation in hostilities and 6 months after return. A comparative assessment of the cellular and humoral state of military personnel of both comparison groups before leaving for an area with an unfavorable operational situation revealed the following differences. In the group of military personnel with allergic manifestations, significantly fewer CD4+ lymphocytes were noted, as well as significantly fewer CD3+CD4+CD25+FoxP3 regulatory lymphocytes and an increase in the number of circulating B lymphocytes were recorded. When dynamically monitoring the parameters of the cellular and humoral immune response in military personnel participating in hostilities, 6 months after returning from a business trip to areas with an unfavorable operational situation, unidirectional changes in the immune status were recorded in the form of a violation of the differentiation processes of the T cell link of the immune system. In the group of servicemen suffering from allergic diseases, the revealed changes were accompanied by a weakening of the processes of physiological immunosuppression in the form of a persistent decrease in the content of regulatory T lymphocytes in the dynamics of observation for 6 months.

Association between TNF-α & IL-6 level changes and remission from depression with duloxetine treatment

Purpose/Aim of the study The pathophysiology of major depressive disorder (MDD) involves multiple factors, including inflammatory processes. This study investigated the relationship between changes in the levels of cytokines and remission in patients with MDD following duloxetine treatment. Materials and methods MDD patients were administered duloxetine for 16 weeks. Clinical evaluation and immunological monitoring were performed every 4 weeks. Results Our results indicated that changes in serum levels of TNF-α and IL-6 were associated with remission following duloxetine treatment in MDD patients. There was a slight increase in TNF-α levels in the first four weeks following duloxetine treatment, which correlated significantly with patients who were in remission. Furthermore, patients in remission exhibited an initial increase in IL-6 levels in the first four weeks, followed by a decrease at 16 weeks. Conclusions These results suggest an important relationship between changes in cytokine levels and remission in patients with major depression after duloxetine treatment.

Performance Capabilities of a Mobile Laboratory for Supporting Immunological Monitoring in Natural Plague Foci

Performance Capabilities of a Mobile Laboratory for Supporting Immunological Monitoring in Natural Plague Foci

Transcription Factor Analysis to Investigate Immunosenescence in Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is linked to various signs of advanced aging, such as premature immunosenescence which occurs due to decline in regenerative ability of T cells. RA T cells develop a unique aggressive inflammatory senescent phenotype with an imbalance of Th17/T regulatory (Treg) cell homeostasis and presence of CD28- T cells. The phenotypic analysis and characterization of T cell subsets become necessary to ascertain if any functional deficiencies exist within with the help of transcription factor (TF) analysis. These subset-specific TFs dictate the functional characteristics of T-cell populations, leading to the production of distinct effector cytokines and functions. Examining the expression, activity, regulation, and genetic sequence of TFs not only aids researchers in determining their importance in disease processes but also aids in immunological monitoring of patients enrolled in clinical trials, particularly in evaluating various T-cell subsets [Th17 (CD3+CD4+IL17+RORγt+) cells and T regulatory (Treg) (CD3+CD4+CD25+CD127-FOXP3+) cells], markers of T-cell aging [aged Th17 cells (CD3+CD4+IL17+RORγt+CD28-), and aged Treg cells (CD3+CD4+CD25+CD127-FOXP3+CD28-)]. In this context, we propose and outline the protocols for assessing the expression of TFs in aged Th17 and Treg cells, highlighting the crucial aspects of this cytometric approach.

Transplant-Acquired Food Allergy in Children.

Organ transplantation in children is a vital procedure for those with end-stage organ failure, but it has been linked to the development of post-transplant allergies, especially food allergies. This phenomenon, known as transplant-acquired food allergy (TAFA), is becoming increasingly recognized, though its mechanisms remain under investigation. Pediatric transplant recipients often require lifelong immunosuppressive therapy to prevent graft rejection, which can alter immune function and heighten the risk of allergic reactions. Our review aimed to gather the latest evidence on TAFA. We conducted a PubMed search from 25 June to 5 July 2024, using specific search terms, identifying 143 articles. After screening, 36 studies were included: 24 retrospective studies, 1 prospective study, 2 cross-sectional researches, and 9 case reports/series. Most studies focused on liver transplants in children. The prevalence of food allergies ranged from 3.3% to 54.3%. Tacrolimus, alongside corticosteroids, was the most commonly used immunosuppressive therapy. In addition to food allergies, some patients developed atopic dermatitis, asthma, and rhinitis. Allergic symptoms typically emerged within a year post-transplant, with common allergens including milk, eggs, fish, nuts, soy, wheat, and shellfish. Both IgE-mediated and non-IgE-mediated reactions were observed, with treatment often involving the removal of offending foods and the use of adrenaline when necessary. Consistent immunological monitoring, such as skin prick tests and IgE level assessments, is essential for early detection and management of allergies in these patients. Understanding the link between transplantation and allergy development is crucial for improving long-term outcomes for pediatric transplant recipients.

Hematopoietic stem cell transplantation for primary immunodeficiency.

Primary immunodeficiencies, also commonly called inborn errors of immunity (IEI), are commonly due to developmental or functional defects in peripheral blood cells derived from hematopoietic stem cells. In light of this, for the past 50 years, hematopoietic stem cell transplantation (HSCT) has been used as a definitive therapy for IEI. The fields of both clinical immunology and transplantation medicine have had significant advances. This, in turn, has allowed for both an increasing ability to determine a monogenic etiology for many IEIs and an increasing ability to successfully treat these patients with HSCT. Therefore, it has become more common for the practicing allergist/immunologist to diagnose and manage a broad range of patients with IEI before and after HSCT. This review aims to provide practical guidance for the clinical allergist/immunologist on the basics of HSCT and known outcomes in selected forms of IEI, the importance of pre-HSCT supportive care, and the critical importance of and guidance for life-long immunologic and medical monitoring of these patients.

Can immunocrit be used as a monitoring tool for swine vaccination and infection studies?

BackgroundThe immunocrit is a cost-effective and straightforward technique traditionally used to assess passive immunity transfer to newborn piglets. However, it has not been previously used for monitoring the effect of vaccination and/or infections. Therefore, this study aimed to evaluate the usefulness of the immunocrit technique as an immunological monitoring tool in a vaccination and challenge scenario, using porcine circovirus 2 (PCV-2) as pathogen model. The immunocrit ratio was monitored in PCV-2 vaccinated (V) and non-vaccinated (NV) 3-week-old piglets (study day 0, SD0) that were subsequently challenged with this virus at SD21 and followed up to SD42. Additional techniques (PCV-2 IgG ELISA, optical refractometry, and proteinogram) were performed to further characterize the results of the immunocrit analysis.ResultsImmunocrit, γ-globulin concentration and PCV-2 S/P values followed similar dynamics: descending after PCV-2 vaccination but ascending after an experimental PCV-2 inoculation. However, statistically significant differences between V and NV animals were only found with the PCV-2 ELISA. In this case, V animals had significantly higher (p < 0.05) S/P values (S/P ratio = 0.74) than NV (S/P ratio = 0.39) pigs only after challenge at SD42. On the other hand, serum total protein obtained by refractometer (STPr) were maintained from SD0 to SD21 and increased in both groups from SD21 to SD42. Correlations between techniques were low to moderate, being the most robust ones found between immunocrit and optical refractometry (ρ = 0.41) and immunocrit with γ-globulins (ρ = 0.39). In a subset of sera, the proteinogram technique was applied to the whole serum and the supernatant of the immunocrit, with the objective to characterize indirectly the immunocrit fraction. The latter one included all protein types detectable through the proteinogram, with percentages varying between 64.3% (γ-globulins) and 82% (β-globulins).ConclusionThe immunocrit technique represented a fraction of the total serum proteins, with low to moderate correlation with all the complementary techniques measured in this study. Its determination at different time points did not allow monitoring the effect of vaccination and/or infection using PCV-2 as a pathogen model.

Using established biorepositories for emerging research questions: a feasibility study

BackgroundProteomics and metabolomics offer substantial potential for advancing kidney transplant research by providing versatile opportunities for gaining insights into the biomolecular processes occurring in donors, recipients, and grafts. To achieve this, adequate quality and numbers of biological samples are required. Whilst access to donor samples is facilitated by initiatives such as the QUOD biobank, an adequately powered biobank allowing exploration of recipient-related aspects in long-term transplant outcomes is missing. Rich, yet unverified resources of recipient material are the serum repositories present in the immunological laboratories of kidney transplant centers that prospectively collect recipient sera for immunological monitoring. However, it is yet unsure whether these samples are also suitable for -omics applications, since such clinical samples are collected and stored by individual centers using non-uniform protocols and undergo an undocumented number of freeze–thaw cycles. Whilst these handling and storage aspects may affect individual proteins and metabolites, it was reasoned that incidental handling/storage artifacts will have a limited effect on a theoretical network (pathway) analysis. To test the potential of such long-term stored clinical serum samples for pathway profiling, we submitted these samples to discovery proteomics and metabolomics.MethodsA mass spectrometry-based shotgun discovery approach was used to obtain an overview of proteins and metabolites in clinical serum samples from the immunological laboratories of the Dutch PROCARE consortium. Parallel analyses were performed with material from the strictly protocolized QUOD biobank.ResultsFollowing metabolomics, more than 800 compounds could be identified in both sample groups, of which 163 endogenous metabolites were found in samples from both biorepositories. Proteomics yielded more than 600 proteins in both groups. Despite the higher prevalence of fragments in the clinical, non-uniformly collected samples compared to the biobanked ones (42.5% vs 26.5% of their proteomes, respectively), these fragments could still be connected to their parent proteins. Next, the proteomic and metabolomic profiles were successfully mapped onto theoretical pathways through integrated pathway analysis, which showed significant enrichment of 79 pathways.ConclusionsThis feasibility study demonstrated that long-term stored serum samples from clinical biorepositories can be used for qualitative proteomic and metabolomic pathway analysis, a notion with far-reaching implications for all biomedical, long-term outcome-dependent research questions and studies focusing on rare events.

Effects of antibiotics, hospitalisation and surgical complications on self-reported immunological vulnerability following paediatric open-heart surgery and thymectomy: a single-centre retrospective cohort study

BackgroundPartial or complete thymectomy is routinely performed in paediatric open-heart surgeries when treating congenital heart defects. Whether or not thymectomised children require systematic immunological monitoring later in life is unknown....

Advanced in immunological monitoring of HIV infection: profile of immune cells and cytokines in people living with HIV-1 in Benin

BackgroundImmune cells and cytokines have been linked to viremia dynamic and immune status during HIV infection. They may serve as useful biomarkers in the monitoring of people living with HIV-1 (PLHIV-1). The present work was aimed to assess whether cytokines and immune cell profiles may help in the therapeutic follow-up of PLHIV-1.MethodsForty PLHIV-1 in treatment success (PLHIV-1s) and fifty PLHIV-1 in treatment failure (PLHIV-1f) followed at the University Hospital of Abomey-Calavi/Sô-Ava in Benin were enrolled. Twenty healthy persons were also recruited as control group. Circulating cytokines and immune cells were quantified respectively by ELISA and flow cytometry.ResultsPLHIV-1 exhibited low proportions of CD4 + T cells, NK, NKT, granulocytes, classical and non-classical monocytes, and high proportions of CD8 + T cells, particularly in the PLHIV-1f group, compared to control subjects. Eosinophils, neutrophils and B cell frequencies did not change between the study groups. Circulating IFN-γ decreased whereas IL-4 significantly increased in PLHIV-1s compared to PLHIV-1f and control subjects even though the HIV infection in PLHIV-1s downregulated the high Th1 phenotype observed in control subjects. However, Th1/Th2 ratio remained biased to a Th1 phenotype in PLHIV-1f, suggesting that high viral load may have maintained a potential pro-inflammatory status in these patients. Data on inflammatory cytokines showed that IL-6 and TNF-α concentrations were significantly higher in PLHIV-1s and PLHIV-1f groups than in control subjects. Significant high levels of IL-5 and IL-7 were observed in PLHIV-1f compared to controls whereas PLHIV-1s presented only a high level of IL-5. No change was observed in IL-13 levels between the study groups.ConclusionOur study shows that, in addition to CD4/CD8 T cell ratio, NK and NKT cells along with IL-6, TNF-α, IL-5 and IL-7 cytokines could serve as valuable immunological biomarkers in the therapeutic monitoring of PLHIV-1 although a larger number of patients would be necessary to confirm these results.

Costs and acceptability of simplified monitoring in HIV-suppressed patients switching to dual therapy: the SIMPL'HIV open-label, factorial randomised controlled trial.

Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences. The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales. Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451];p= 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48. Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment. ClinicalTrials.govNCT03160105.

Intradermal Naked DNA Vaccination by DNA Tattooing for Mounting Tumor-Specific Immunity in Stage IV Melanoma Patients: A Phase I Clinical Trial

Introduction: Naked DNA vaccination could be a powerful and safe strategy to mount antigen-specific cellular immunity. We designed a phase I clinical trial to investigate the toxicity of naked DNA vaccines encoding CD8+ T-cell epitope from tumor-associated antigen MART-1 in patients with advanced melanoma. Methods: This dose escalating phase Ia clinical trial investigates the toxicity and immunological response upon naked DNA vaccines encoding a CD8+ T-cell epitope from the tumor-associated antigen MART-1, genetically linked to the gene encoding domain 1 of subunit-tetanus toxin fragment C in patients with advanced melanoma (inoperable stage IIIC-IV, AJCC 7th edition). The vaccine was administrated via intradermal application using a permanent make-up or tattoo device. Safety was monitored according to CTCAE v.3.0 and skin biopsies and blood samples were obtained for immunologic monitoring. Results: Nine pretreated, HLA-A*0201-positive patients with advanced melanoma expressing MART-1 and MHC class I, with a good performance status, and adequate organ function, were included. With a median follow-up of 5.9 months, DNA vaccination was safe, without treatment-related deaths. Common treatment-emergent adverse events of any grade were dermatologic reactions at the vaccination site (100%) and pain (56%). One patient experienced grade 4 toxicity, most likely related to tumor progression. One patient (11%) achieved stable disease, lasting 353 days. Immune analysis showed no increase in vaccine-induced T cell response in peripheral blood of 5 patients, but did show a MART-1 specific CD8+ T cell response at the tattoo administration site. The maximum dose administered was 2 mg due to lack of clinical activity. Conclusion: We showed that the developed DNA vaccine, applied using a novel intradermal application strategy, can be administered safely. Further research with improved vaccine formats is required to show possible clinical benefit of DNA vaccination.

Adherence of HIV/AIDS patients to clinical outcome in Semarang City

Background: The success of HIV therapy can be measured by clinical, immunological, and virological monitoring. Meanwhile, low adherence to antiretroviral therapy (ART) contributes significantly to the disease progression and emergence of drug-resistant HIV. Objective: This study aimed to determine the correlation between the adherence of HIV/AIDS patients to clinical outcomes in Semarang. Method: This was an observational and cross-sectional approach. The instrument used the Simple Medication Adherence Questionnaire (SMAQ), which was validated and distributed to 50 respondents. The data were analyzed using chi-square (p &lt; 0.05), and the results showed a statistically significant relationship. Result: Respondents were male (96%), aged 26-45 years (76%), high school graduates (24%), working (88%), single (86%), without comorbidity (86%), length of treatment more than 12 months (80%), and general treatment (50%). A total of 31 respondents (62%) adhered to treatment with the combination regimen of Tenofovir/Lamivudine/Efavirenz (20%). There was a significant relationship (p = 0.006) between the length of treatment and patient adherence. The adherence results were not significantly related (p &gt; 0.05) to virological outcomes. Conclusion: There is no significant relationship between the adherence of HIV/AIDS patients and clinical outcomes.

Natural Anti-aging Skin Care: Role and Potential

The first and most noticeable indication of the ageing process, which becomes more pronounced as one ages, is the decline of skin morphology and physiology.The essential functions of the skin, including homodynamic regulation of body temperature, fluid balance, loss of electrolytes and proteins, and vitamin D generation, are all impacted by this degradation. elimination of waste, immunological monitoring, sensory perception, and defence of other organs from harmful environmental elements. Consumers are now aware that regular cosmetics contain toxic chemicals and other dangerous substances. Because more people are demanding healthier options, the natural beauty business is growing because to cutting-edge technology and high-performance ingredients. Thus, this review's objectives are to provide some important insights into how inherent and extrinsic factors affect excessive or premature skin ageing. In this we’ll know about natural agents like Green Tea, Licorice, Rosemary Jojoba Leaves ,Ashwagandha , shatavari as anti-ageing from various plant sources such root, leaves, seeds , flowers and so on which can be explored as anti-ageing skincare. Which basically beneficial in skincare. Keywords: Skin, Anti- Ageing, Natural Agents, Role of Agents

Cohort profile: PRESTIGIO, an Italian prospective registry-based cohort of people with HIV-1 resistant to reverse transcriptase, protease and integrase inhibitors

PurposeThe PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes...

Method of goat immunodiagnosis in arthritis-encephalitis

Currently, serological tests are used in the diagnosis of Caprine Arthritis Encephalitis (CAE), but a more accurate diagnosis of the disease requires the most reliable modern methods of immunodiagnosis. This is important for timely diagnosis and prevention of this disease, especially in commercial production of goat milk. At the present stage, the practice of infectious diseases immunodiagnosis in animals includes the determination of cytokines 6 and 10. The discovered cytokines allow for a different view on the infectious disease pathogenesis, while the previously used diagnostic methods are not excluded from the veterinary practice. At present, during the restoration and renewal of the goat population, new breeds purchased in foreign countries have appeared, and with them have come new diseases not previously prevalent in the Russian Federation. Therefore, practicing veterinarians need to develop the most effective immunodiagnostic tests for these diseases and work out effective control and prevention methods, as well as to be able to assess the risks of new infections or mixt infections. Immunophenotyping is performed in various infectious animal diseases, and immunological monitoring is also possible.

Detection of anti-SARS-CoV-2 salivary antibodies in vaccinated adults.

Since the introduction of efficient anti-SARS-CoV-2 vaccines, the detection of antibodies becomes useful for immunological monitoring and COVID-19 control. Therefore, this longitudinal study aimed to evaluate the detection of SARS-CoV-2 antibodies in the serum and saliva of COVID-19-vaccinated adults. The study included 13 not vaccinated and 35 vaccinated participants with two doses of CoronaVac (Sinovac/Butantan) vaccine who subsequently received BNT162b2 (Pfizer-BioNTech) vaccine as a booster dose. Vaccinated participants donated saliva and serum in three different time points. Enzyme-linked immunosorbent assay was used for antibody detection. In our results, the serum neutralizing antibodies (NAb) were detected in 34/35 samples after second dose and in 35/35 samples one and five months after the booster dose. In saliva, NAb were detected in 30/35 samples after second dose and in 35/35 of samples one and five months after the booster dose. IgA was detected in 19/34 saliva samples after second dose, in 18/35 one month after the booster and in 30/35 five months after. IgG in saliva was detected in 1/34 samples after second dose, 33/35 samples one month after the booster dose and in 20/35 five months after. A strong correlation was found between IgG and neutralizing activity in saliva, and salivary IgA would be a sign of recent exposure to the virus. In conclusion, saliva can be suitable for monitoring antibodies anti-SARS-CoV-2 after vaccination. Heterologous vaccination contributed to increase anti-SARS-CoV-2 antibodies in the Brazilian health context. Complementary studies with large groups are mandatory to conclude the interest in following mucosal immunity.

Infection Risk, Mortality, and Hypogammaglobulinemia Prevalence and Associated Factors in Adults Treated with Rituximab: A Tertiary Care Center Experience.

Rituximab is a human monoclonal antibody directed against the B-cell transmembrane protein CD20. Although well-tolerated, given its mechanism of action, rituximab can induce a state of severe immunosuppression, increasing the risk of opportunistic and fulminant infection and mortality. To evaluate the risk of infection, mortality, and hypogammaglobulinemia and their associated factors among rituximab receivers. This was a single-center retrospective cohort study of adults treated with rituximab for various indications. Hypogammaglobulinemia was defined by a cut-off value below the normal limit (an IgG level of <7.51 g/L, an IgM level of <0.46 g/L, and/or an IgA level of <0.82 g/L). Patients who met the definition of hypogammaglobinemia solely based on IgA were excluded. Severe infection was defined as any infection that required intensive care unit admission. A total of 137 adults with a mean age of 47.69 ± 18.86 years and an average BMI of 28.57 ± 6.55 kg/m2 were included. Hematological malignancies and connective tissue diseases were the most common primary diagnoses for which rituximab was used. More than half of the patients received the 375 mg/m2 dose. Rituximab's mean cumulative dose was 3216 ± 2282 mg, and the overall mortality rate was 22.6%. Hypogammaglobulinemia was diagnosed in 43.8% of the patients, and it was significantly more prevalent among males and the 375 mg/m2 and 500 mg doses. Hematological malignancy was the only predictor for infection. Patients with blood type AB or B, hematological malignancies, and corticosteroids had a significantly higher mortality rate. Receiving the 1000 mg dose and having a low CD19 were associated with a significantly lower risk of infection and mortality, respectively. Hypogammaglobulinemia was diagnosed in 43.8% of the patients, and it was significantly more common among males and the 375 mg/m2 and 500 mg doses. Hematological malignancies were significantly associated with higher infection and mortality rates, while corticosteroids were significantly associated with a higher mortality. Since the culprit of mortality was infection, these findings highlight the critical need for more frequent immunological monitoring during rituximab treatment period to mitigate the burden of infection and identify candidates for immunoglobulin replacement.