Presence Of Immunoglobulin Research Articles

Ocular Surface plasmacytoma

Conjunctival plasmacytomas are rare tumours that may be solitary or related with multiple myeloma (MM), a malignant systemic plasma cell neoplasm that tends to metastasize. Plasma cell infiltration of bone marrow and presence of immunoglobulin is characteristic of MM. It may cause extraskeletal spread being the ocular tissue involvement very rare. We report a case of a 57-year-old male patient affected of a caruncular mass that has increased of volume in the past two months. The patient was previously diagnosed of extramedullar affection of MM and he had no treatment in that moment. An excisional biopsy confirmed the diagnostic of a conjunctival plasmacytoma secondary to MM Immunoglobulin D (IgD). Second line systemic chemotherapy treatment produced total regression. Ocular surface plasmacytoma is an uncommon entity that has to be suspected in a known myeloma patient with a conjunctival mass growth, including the caruncle. The presence of conjunctival plasmacytoma may be a sign of recurrence and insufficient chemotherapy as showed our case. Therefore, regular ophthalmological examinations should be done to the myeloma patients without any treatment.

Chlamydia pneumoniae and Helicobacter pylori infections and immunological profile of community-dwelling older adults.

Chronic bacterial infections are associated with changes in the immunosenescence process and immunological biomarkers can assist in monitoring these changes. The identification of this immunological profile is important because Chlamydia pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori) infections are important factors of morbidity and mortality among the older adults. This study aimed to identify changes in the immunological profile in the presence of C. pneumoniae and H. pylori infections among community-dwelling older adults. This is a cross-sectional study that used data from 1432 participants from the Bambuí Cohort Study of Aging, Minas Gerais, Brazil. The presence of immunoglobulin G (IgG) for C. pneumoniae and H. pylori was considered a dependent variable and assessed in the participants' serum using the enzyme-linked immunosorbent assay (ELISA). In assessing the immunological profile, the following inflammatory markers were considered: CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-1β, IL-6, IL-10, IL-12, TNF, and CRP. Associations were assessed by logistic regression, estimating odds ratios and confidence intervals (95%) using the Stata® V.13.1 software. The seroprevalence of anti-C. pneumoniae and anti-H. pylori antibodies was 55.9% and 70.3%, respectively. While high levels of anti-C. pneumoniae antibodies were associated with higher concentrations of CXCL10 and IL-10, higher levels of IL-1β and IL-6 were inversely associated with the titration of anti-H. pylori antibodies. The results characterize immunological profiles associated with these chronic infections and reinforce the potential effects of biomarkers on infections by these bacteria and on the immunosenescence process.

Frequency of Cutaneous Disorders in Patients With Celiac Disease.

Background and objectiveCeliac disease is an autoimmune multisystem disorder that is triggered by dietary gluten sensitivity in genetically susceptible individuals. It presents with extraintestinal cutaneous manifestations including dermatitis herpetiformis (DH), atopic dermatitis, psoriasis, urticaria, and alopecia areata. Due to the insufficient availability of data, this study aimed to estimate the frequency of cutaneous manifestation in a Pakistani population with celiac disease.MethodsThis cross-sectional study was conducted from January 2020 to July 2021, and 300 patients with a confirmed diagnosis of celiac disease were enrolled in the study from the internal medicine department of a tertiary care hospital in Pakistan. Celiac disease was confirmed by the presence of immunoglobulin A (IgA) endomysial antibody and IgA tissue transglutaminase antibody. The presence of cutaneous manifestations was assessed with the assistance of a qualified dermatologist and noted in a self-structured questionnaire.ResultsOverall, the most common cutaneous manifestation was DH (16.0%), whereas the second most common cutaneous manifestation was psoriasis (13.8%). DH was most commonly found among males (18.9%), while psoriasis was more common among females (14.12%).ConclusionAmong the various cutaneous presentations in patients with celiac disease, the most common dermatological manifestation was DH. Therefore, patients with cutaneous manifestations should undergo screening for celiac disease.

Whole-genome sequencing facilitates patient-specific quantitative PCR-based minimal residual disease monitoring in acute lymphoblastic leukaemia, neuroblastoma and Ewing sarcoma

BackgroundMinimal residual disease (MRD) measurement is a cornerstone of contemporary acute lymphoblastic leukaemia (ALL) treatment. The presence of immunoglobulin (Ig) and T cell receptor (TCR) gene recombinations in leukaemic clones allows widespread use of patient-specific, DNA-based MRD assays. In contrast, paediatric solid tumour MRD remains experimental and has focussed on generic assays targeting tumour-specific messenger RNA, methylated DNA or microRNA.MethodsWe examined the feasibility of using whole-genome sequencing (WGS) data to design tumour-specific polymerase chain reaction (PCR)-based MRD tests (WGS-MRD) in 18 children with high-risk relapsed cancer, including ALL, high-risk neuroblastoma (HR-NB) and Ewing sarcoma (EWS) (n = 6 each).ResultsSensitive WGS-MRD assays were generated for each patient and allowed quantitation of 1 tumour cell per 10−4 (0.01%)–10–5 (0.001%) mononuclear cells. In ALL, WGS-MRD and Ig/TCR-MRD were highly concordant. WGS-MRD assays also showed good concordance between quantitative PCR and droplet digital PCR formats. In serial clinical samples, WGS-MRD correlated with disease course. In solid tumours, WGS-MRD assays were more sensitive than RNA-MRD assays.ConclusionsWGS facilitated the development of patient-specific MRD tests in ALL, HR-NB and EWS with potential clinical utility in monitoring treatment response. WGS data could be used to design patient-specific MRD assays in a broad range of tumours.

MM-402: The Prevalence of Kappa and Lambda Chains in the Elderly Population. Experience of a Single Center in Southern Brazil in 7,154 Cases

Introduction The study of multiple myeloma and other related diseases, such as gammopathies, has long been based on clinical aspects and the determination of GI levels, bone X-rays, and bone marrow aspirations. However, no lab tests exist that we could call a “predictive lab test.” As we have begun to routinely determine the levels of free light chains (kappa and lambda), we could use different protocols to prevent and treat certain gammopathies based on these determinations. Considering what has already been published about the prevalence of these laboratory tests, we decided to start a program in our laboratory to demonstrate to doctors the importance of these tests in the diagnosis and follow-up of elderly patients. We decided to look for five main situations that we encountered in the lab, as follows: IgG kappa, IgG lambda, IgA kappa, or IgA lambda together with high levels of immunoglobulins, and the presence of only kappa and lambda chains, without the presence of immunoglobulins. We also examined correlations between test results and gender and age. Methods The DASA Laboratory is among the largest laboratories in Brazil, with more than two thousand collection centers throughout the country. We analyzed a total of 7,154 samples over a three-month period. All tests were done in our Department of Hematology, using protein electrophoresis. We obtained positive tests for 1,144 men and 947 women. We did a retrospective analysis of age and sex and identified a very accurate relationship between test results and age. From 50 to 85 years, in both sexes, an increase in positive results was observed, amounting to three times as many as those in younger patients. Conclusion Considering this result, we have already established our first step to evaluate not only free light chains but also free heavy chains as one of the most important tests with a strong predictive value for patient follow-up.

Disorder of Iron Metabolism as a Universal Pathogenetic Factor in Damage to Organs and Systems in Covid-19

Relevance. The pathogenesis of COVID-19 remains one of the most pressing. The literature discusses the role of iron as a factor supporting inflammatory processes, hypercoagulability and microcirculation crisis in severe COVID-19.The aim of study. was to identify changes in iron metabolism in patients with severe COVID-19 and hyperferritinemia.Material and methods. In this study, we used a content analysis of available scientific publications and our own observations of the peculiarities of the clinical picture and laboratory parameters in patients with a severe course of COVID-19 who had hyperferretinemia at the height of the disease. The main group consisted of 30 patients hospitalized in the Department of Anesthesiology, Resuscitation and Intensive Care of N.A. Semashko City clinical Hospital No. 38 with the diagnosis COVID-19, bilateral polysegmental pneumonia, severe course and hyperferritinemia. The diagnosis of a new coronavirus infection was confirmed by visualization of bilateral viral lung lesions with chest CT-scan, positive PCR test for SARS-CoV-2 and the presence of immunoglobulins to SARS-CoV-2. The control group consisted of 20 healthy volunteers. The study evaluated the biochemical parameters of iron metabolism, fibrinolysis and markers of inflammation. Changes associated with impaired iron metabolism were assessed by the level of serum iron, transferrin, daily and induced iron excretion in the urine. Statistical processing was carried out using nonparametric methods.Results. All patients with severe COVID-19 and hyperferritinemia showed signs of impaired iron metabolism, inflammation and fibrinolysis — a decrease in the level of transferrin (p<0.001), serum iron (p><0.005), albumin (p><0.001), lymphocytes (p><0.001) and an increase in leukocytes (p><0.001), neutrophils (p><0.001), CRP (p><0.005), IL-6 (p><0.001), D-dimer (p><0.005), daily urinary iron excretion (p><0.005) and induced urinary iron excretion (p><0.001). Conclusions The study showed that in the pathogenesis of the severe course of COVID-19, there is a violation of iron metabolism and the presence of a free iron fraction. The appearance of free iron can be caused by damage to cells with the “release” of iron from cytochromes, myoglobin, hemoglobin, or violation of the binding of iron to transferrin, which may be the result of a change in the protein structure or violation of the oxidation of iron to the trivalent state. When assessing the degree of viral effect on the body, one should take into account the effect of various regulators of iron metabolism, as well as an assessment of the level of free iron not associated with transferrin. Keywords: new coronavirus infection, COVID-19, SARS-CoV-2, iron metabolism, free iron, ferritin, transferrin, NTBI, nontransferrin bound iron>˂0.001), serum iron (p˂0.005), albumin (p˂0.001), lymphocytes (p˂0.001) and an increase in leukocytes (p˂0.001), neutrophils (p˂0.001), CRP (p˂0.005), IL-6 (p˂0.001), D-dimer (p˂0.005), daily urinary iron excretion (p˂0.005) and induced urinary iron excretion (p˂0.001).Conclusions. The study showed that in the pathogenesis of the severe course of COVID-19, there is a violation of iron metabolism and the presence of a free iron fraction. The appearance of free iron can be caused by damage to cells with the “release” of iron from cytochromes, myoglobin, hemoglobin, or violation of the binding of iron to transferrin, which may be the result of a change in the protein structure or violation of the oxidation of iron to the trivalent state. When assessing the degree of viral effect on the body, one should take into account the effect of various regulators of iron metabolism, as well as an assessment of the level of free iron not associated with transferrin.

Impact of Humoral Immunogenicity (Anti-mCAR19 Antibodies) on CTL019 Cellular Kinetics, Efficacy, and Safety

Background: The humoral immunogenicity of CAR19, a chimeric antigen receptor with a murine scFV domain developed for treatment with CTL019 (tisagenlecleucel) in relapsed/refractory (R/R) pediatric and young adult acute lymphoblastic leukemia (ALL), was evaluated in 2 studies (ELIANA [NCT02435849]; ENSIGN [NCT02228096]). To date, little is known about the presence and impact of preexisting or treatment-induced anti-murine (m)CAR19 antibodies in patients treated with CAR T-cell therapy.Methods: Anti-mCAR19 antibodies were measured in patients from ELIANA and ENSIGN trials before and after CTL019 infusion to evaluate the impact of anti-mCAR19 antibodies on cellular kinetics, efficacy, and safety. Data were pooled from ELIANA (n = 68) and ENSIGN (n = 29). Anti-mCAR19 antibodies were captured by mCAR19-transfected Jurkat cells and wild-type Jurkat cells. Following incubation and washing, an R-phycoerythrin (PE)-labeled anti-IgG/M F(ab')2 fragment was added for detection of anti-mCAR19 antibodies using flow cytometry and reported as median fluorescence intensity (MFI). Exploratory assay development included assessment of whether the presence of immunoglobulins after IVIG therapy in clinical samples would interfere with the anti-mCAR19 antibody assay. Impact of preexisting immunogenicity, as detected by MFI levels, was evaluated using cellular kinetic, efficacy, and safety endpoints. The impact of treatment-induced immunogenicity (defined as having an increase in anti-mCAR19 antibody levels over baseline) was assessed by calculating the fold change between preexisting (ie, baseline) levels and postinfusion levels.Results: Approximately 90% of patients displayed preexisting anti-mCAR19 antibodies; a similar incidence was detected in healthy volunteer samples, as observed during assay development. Approximately 35% of patients developed treatment-induced anti-mCAR19 antibodies. No apparent relationship between CTL019 expansion (AUC0-28d) and preexisting or treatment-induced anti-mCAR19 antibodies was identified (r2 < 0.001 and r2 = 0.006, respectively); similar results were seen for Cmax (Figure 1a). Presence of anti-mCAR19 after infusion did not appear to influence the persistence of transgene or day 28 response (Figure 1b). Kaplan-Meier curves showed that the presence of preexisting and treatment-induced anti-mCAR19 antibodies did not appear to impact the duration of response or event-free survival (Figure 1c). Strip plots showed consistent levels of preexisting and treatment-induced anti-mCAR19 antibodies across patients with safety events (grade 0/1/2/3/4), including CRS, neutropenia, thrombocytopenia, and neurological events. There was no apparent relationship between treatment- induced anti-mCAR19 antibodies with B-cell recovery categories (recovery ≤ 3 months, > 3 months and ≤ 6 months, > 6 months, and ongoing sustained B-cell aplasia). There was also no association in patients at the time of B-cell recovery with the presence of treatment-induced anti-mCAR19 antibodies following CTL019 infusion. B-cell aplasia requiring immunoglobulin replacement therapy (IVIG) occurred following CTL019 in the majority of patients. The CTL019 concentration time profiles for patients with treatment-induced anti-mCAR19 antibodies were categorized by the time following IVIG administration (within 1 week, 2 weeks, or > 3 weeks of IVIG administration). The results revealed no impact of the time at which IVIG was administered on the in vivo expansion and persistence of the transgene.Conclusions: We report the first comprehensive assessment of the impact of anti-mCAR antibodies on clinically relevant endpoints for CAR therapy. Determination of immunogenicity is an important endpoint required by health authorities for biologic drugs, and these analyses demonstrate the importance of characterizing the impact on clinical endpoints for CAR therapies. These analyses in patients with pediatric R/R ALL revealed a surprisingly high frequency of baseline anti-mCAR19 antibodies and showed that the presence of preexisting and treatment-induced anti-mCAR19 antibodies did not impact the cellular kinetics, safety, and efficacy of CTL019. Cell-mediated immunity studies are ongoing. [Display omitted] DisclosuresMueller:Novartis Pharmaceuticals Corporation: Employment. Waldron:Novartis Pharmaceuticals Corporation: Employment. Sickert:Novartis Institutes for BioMedical Research: Employment. Grupp:University of Pennsylvania: Patents & Royalties; Novartis Pharmaceuticals Corporation: Consultancy, Other: grant; Adaptimmune: Consultancy; Jazz Pharmaceuticals: Consultancy. Maude:Novartis Pharmaceuticals: Consultancy, Other: Medical Advisory Boards. Levine:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. Laetsch:Novartis Pharmaceuticals Corporation: Consultancy. Pulsipher:Novartis Pharmaceuticals Corporation: Consultancy, Other: Phase II steering committee; Chimerix: Other: Advisory board Dec 2015; Jazz Pharmaceuticals: Other: advisory board, education; CSL Behring: Other: advisory board Feb 2017; Adaptive: Other: Advisory board 6/17. Boyer:Novartis Pharmaceuticals Corporation: Honoraria. August:Novartis Pharmaceuticals Corporation: Consultancy. Awasthi:Novartis Pharmaceuticals Corporation: Employment. Levine:GE Healthcare: Consultancy; Novartis Pharmaceuticals Corporation: Patents & Royalties, Research Funding; Brammer Bio: Consultancy; Tmunity Therapeutics: Equity Ownership, Research Funding. June:WIRB/Copernicus Group: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celldex: Honoraria, Membership on an entity's Board of Directors or advisory committees; Immune Design: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Novartis: Patents & Royalties, Research Funding; Tmunity Therapeutics: Equity Ownership, Research Funding. Taran:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Wood:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Myers:Novartis Pharmaceuticals Corporation: Consultancy.

Parvovirus B19 in Pregnancy: A Case Review.

Parvovirus B19 has been identified as the cause of erythema infectiosum, a common childhood illness. Also known as fifth disease, this virus is highly contagious among school-age children, especially during the winter months when outbreaks within classrooms are widespread. The majority of adults have had the infection in childhood and are immune to recurrence. Approximately 40% of childbearing-age individuals, however, remain nonimmune and susceptible to infection. If acquired during pregnancy, parvovirus B19 infection can have devastating fetal consequences, especially if contracted in the second trimester. Vertical transmission of parvovirus B19 occurs more readily during this gestational period, and fetal loss rates of 8% to 17% have been reported as a result of severe fetal anemia and hydrops fetalis. Unfortunately, adults with parvovirus B19 infection are often asymptomatic and do not exhibit the classic slapped-cheek rash seen in childhood. More commonly, adults will exhibit atypical symptoms such as joint arthralgias. Maternal history of direct exposure to a confirmed case within the family or the presence of atypical symptoms warrants serum antibody screening. Although the presence of immunoglobulin G confirms immunity, any immunoglobulin M positivity will require ongoing fetal surveillance for evidence of fetal anemia and hydrops fetalis. Serial ultrasound imaging for 8 to 12 weeks with Doppler measurements of the peak systolic velocity in the middle cerebral artery are the mainstays of fetal monitoring. Referral to a maternal-fetal medicine specialist with experience in fetal blood sampling and intrauterine transfusion is recommended for any cases of hydrops fetalis or if a concern for severe fetal anemia exists.

Human and animal cystic echinococcosis in Tataouine governorate: hypoendemic area in a hyperendemic country, myth or reality?

BackgroundCystic echinococcosis (CE) has a worldwide distribution and is especially prevalent in North African countries. With a mean annual surgical incidence (ASI) of CE of 12.7 per 100,000 inhabitants, Tunisia is one of the most CE endemic countries in the Mediterranean area. Tataouine governorate is considered to be the most CE hypoendemic region in Tunisia (ASI = 0.92) despite favourable socioeconomic conditions that enable maintenance of the Echinococcus granulosussensu lato (s.l.) life-cycle and a significant environmental contamination with E. granulosuss.l. eggs. The aim of this study was to assess human CE seroprevalence, prevalence of CE in food animals and environmental contamination by E. granulosus s.l. eggs in different districts of Tataouine governorate.MethodsThis study was conducted from January to December 2018. A total of 374 human sera samples were tested for the presence of immunoglobulin G antibodies against E. granulosus using a commercial ELISA kit. Specimens were also collected from animals slaughtered at the Tataouine abattoir (n = 8609) and examined for the presence of hydatid cysts; 111 hydatid cysts were genotyped. Eggs of E. granulosuss.l. were identified by PCR and DNA sequencing from dog faecal samples (n = 288).ResultsSerological tests showed that 8.5% of the sera samples tested were positive for E. granulosus-specific antibodies. The average prevalence of hydatidosis in livestock was 1.6%, and CE infection was more prevalent in cattle than in sheep, goats and dromedaries. The contamination rate of dog faeces by E. granulosus sensu stricto eggs varied significantly from 0 to 23.5% depending on the collection area. Molecular analyses only revealed the presence of the G1 genotype for cysts and eggs.ConclusionsBased on our findings, CE is likely to be more endemic in the Tataouine governorate than previously described. Thus, to implement an effective control programme against CE, a national survey should be carried out to determine human CE prevalence in the different Tunisian governorates.Graphical

Biological stratification of clinical disease courses in childhood immune thrombocytopenia

BackgroundIn childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes. ObjectiveTo predict the response to intravenous immunoglobulins (IVIg) and ITP disease course using genetic and immune markers. MethodsChildren aged younger than 7 years with newly diagnosed ITP (N = 147) from the Treatment With or Without IVIG for Kids with ITP study were included, which randomized children to an IVIg or observation group. A total of 46 variables were available: clinical characteristics, targeted genotyping, lymphocyte immune phenotyping, and platelet autoantibodies. ResultsIn the treatment arm, 48/80 children (60%) showed a complete response (platelets ≥100 × 109/L) that lasted for at least 1 month (complete sustained response [CSR]) and 32 exhibited no or a temporary response (absence of a sustained response [ASR]). For a biological risk score, five variables were selected by regularized logistic regression that predicted ASR vs CSR: (1) hemoglobin; (2) platelet count; (3) genetic polymorphisms of Fc‐receptor (FcγR) IIc; (4) the presence of immunoglobulin G (IgG) anti‐platelet antibodies; and (5) preceding vaccination. The ASR sensitivity was 0.91 (95% confidence interval, 0.80‐1.00) and specificity was 0.67 (95% confidence interval, 0.53‐0.80). In the 67 patients of the observation arm, this biological score was also associated with recovery during 1 year of follow‐up. The addition of the biological score to a predefined clinical score further improved the discrimination of favorable ITP disease courses. ConclusionsThe prediction of disease courses and IVIg treatment responses in ITP is improved by using both clinical and biological stratification.

Cytomegalovirus and herpes simplex type 1 infections and immunological profile of community-dwelling older adults.

Chronic infections, such as cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1), contribute to the inflammation process among older adults and are associated with the immunosenescence process. The aim was to identify the immunological profile associated with CMV and HSV-1 infections among older adults. This is a cross-sectional study, carried out with 1492 participants from the Bambuí Cohort Study of Aging - Minas Gerais, Brazil. For analysis purposes, we considered the presence of immunoglobulin G (IgG) for CMV and HSV-1 in the participants' serum, assessed by the enzyme-linked immunosorbent assay (ELISA); outcomes were defined by titration above the median (>160 UR/mL for HSV-1 and >399.5U/mL for CMV). In order to assess the immunological profile, the following biomarkers were considered: IL-1beta, IL-10, IL-12, TNF, CXCL8, CXCL9, CXCL10, CCL2, CCL5, IL-6 and CRP; the first four being categorized as detectable levels or not, and the others using the Classification and Regression Tree (CART) method. The analysis was adjusted for sociodemographic variables, health behaviors and health conditions. The seroprevalence of anti CMV and anti HSV-1 antibodies was 99.4% and 97.0%, respectively. Higher concentrations of CXCL8 and CCL5 chemokines were associated with lower antibody titers for CMV, and higher concentrations of CXCL9, IL-6 and CRP were associated with higher levels of antibodies to CMV. Moreover, intermediate levels of CXCL10 were also associated with higher levels of antibodies to CMV. In HSV-1 infection, intermediate levels of CXCL9, CCL5 and IL-6 were less likely to have higher antibody titers for this infection. On the other hand, higher levels of CXCL10 and CRP were positively associated with higher antibody titers for HSV-1. The results describe important immunological changes and reinforce the potential effect of CMV and HSV-1 on the immunosenescence process.

Practical recognition tools of immunoglobulin G serum antibodies against the myelin oligodendrocyte glycoprotein‐positive optic neuritis and its clinical implications

AbstractMyelin oligodendrocyte glycoprotein (MOG)‐associated disease is an autoimmune disease of the central nervous system, associated with the presence of immunoglobulin G serum antibodies against MOG. Recent data have allowed characterization of the clinical spectrum of MOG‐associated disease, which is now considered a new disease entity, distinct from multiple sclerosis and neuromyelitis optica spectrum disorders. Optic neuritis is the most common clinical presentation of MOG‐associated disease in adults, both at disease onset and during the disease course, and has several distinct clinical and paraclinical features. Immunoglobulin G serum antibodies against MOG‐positive optic neuritis is often bilateral and associated with optic disc swelling and a longitudinally extensive abnormal magnetic resonance imaging signal involving the retrobulbar portion of the optic nerve. The visual acuity during the acute attack is severely decreased, and the response to corticosteroids is often rapid and prominent. However, early relapses after steroid cessation are common, and a subset of patients is left with a permanent visual disability. In this review, we discuss the clinical and paraclinical features of immunoglobulin G serum antibodies against MOG‐positive optic neuritis in adults, and focus on the distinctive features that can enable its early diagnosis. Therapeutical considerations at the acute stage and for relapse prevention are further deliberated.

Doença de Kawasaki e COVID-19: uma revisão de literatura

Objetivo: Identificar a relação entre a Doença de Kawasaki e o novo Coronavírus (COVID-19). Revisão bibliográfica: Foram analisados 91 artigos, sendo 39 lidos integralmente e utilizados neste estudo. A análise viabilizou a percepção de que infecções pelo novo Coronavírus levam a uma resposta hiperinflamatória ou tempestade de citocinas, como interleucinas (IL) 1 e 6, ativação de macrófagos e presença de imunoglobulina (Ig) A, provocando patologias como linfohistiocitose hemofagocítica secundária, Síndrome de Disfunção Respiratória Aguda (SDRA) e alterações nas artérias coronarianas semelhantes à Doença de Kawasaki. O dano epitelial provocado pelo vírus em estágio inicial, assim como na DK, pode induzir à endotelite local secundária, o que pode explicar um fenótipo vasculítico autoinflamatório tardio com regulação positiva de interleucinas. Essa inflamação endotelial aumentada e lesão/disfunção após a infecção pelo novo Coronavírus, provavelmente, é devido à ação da enzima conversora de angiotensina (ECA). Considerações finais: Nos últimos 20 anos, os vírus da família dos Coronavírus foram propostos como participantes na patogênese da doença de Kawasaki (DK), uma vasculite sistêmica aguda. A associação documentada levanta a preocupação de saber se a infecção por COVID-19 aumenta o risco de DK.

Demographic and climatic factors associated with dengue prevalence in a hyperendemic zone in Mexico: an empirical approach.

Many models for predicting dengue epidemics use incidence and short-term changes in climate variables, however, studies in real-life scenarios for correlations of seroprevalence (SP) with long-term climate variables and with integration of socio-economic factors are scarce. Our objective was to analyse the combined correlation between socio-economic and climate variables with the SP of dengue in Mexico. We performed a seroepidemiological ecological study on the Mexican Pacific coast. Dengue SP was estimated by the presence of immunoglobulin G antibodies in 1278 inhabitants. We implemented multiple correlations with socio-economic, climatic and topographic characteristics using logistic regression, generalized linear models and non-linear regressions. Dengue SP was 58%. The age-adjusted correlation was positive with the male sex, while a negative correlation was seen with socio-economic status (SES) and scholl level (SL). The annual temperature showed a positive correlation, while the altitude was negative. It should be noted that these correlations showed a marked 'S' shape in the non-linear model, suggesting three clearly defined scenarios for dengue risk. Low SES and SL showed an unexpected paradoxical protective effect. Altitude above sea level and annual temperature are the main determinants for dengue in the long term. The identification of three clearly delineated scenarios for transmission could improve the accuracy of predictive models.

SARS-CoV-2–Induced Kawasaki-Like Hyperinflammatory Syndrome: A Novel COVID Phenotype in Children

We describe 2 children with persistent fever and profuse diarrhea who developed signs of mucocutaneous involvement (conjunctivitis, fissured lips, skin rash, erythema, and edema of the hands and feet). Blood tests revealed elevated markers of inflammation, lymphopenia, thrombocytopenia, and complement consumption. Afterward, diffuse edema with hypoalbuminemia appeared in the context of a capillary leak syndrome. In both patients, repeated nasal swabs were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but each patient had high titers of immunoglobulin G and immunoglobulin M against the SARS-CoV-2 virus. The negative PCR results in the presence of immunoglobulin M and immunoglobulin G suggested that the inflammatory response developed in the late phase of viral infection, when SARS-CoV-2 was not detectable in the upper airway. In this report, we describe patients with what we propose to name as SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome. SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome seems to be caused by a delayed response to SARS-CoV-2. It resembles Kawasaki disease complicated by macrophage activation syndrome, although it has peculiar features, such as prodromal diarrhea, capillary leak syndrome, and myocardial dysfunction. Intravenous corticosteroid treatment appears to be helpful.

Anesthesiologists' and Intensive Care Providers' Exposure to COVID-19 Infection in a New York City Academic Center: A Prospective Cohort Study Assessing Symptoms and COVID-19 Antibody Testing.

Protecting first-line health care providers against work-related coronavirus disease 2019 (COVID-19) infection at the onset of the pandemic has been a crucial challenge in the United States. Anesthesiologists in particular are considered at risk, since aerosol-generating procedures, such as intubation and extubation, have been shown to significantly increase the odds for respiratory infections during severe acute respiratory syndrome (SARS) outbreaks. This study assessed the incidence of COVID-19-like symptoms and the presence of COVID-19 antibodies after work-related COVID-19 exposures, among physicians working in a large academic hospital in New York City (NYC). An e-mail survey was addressed to anesthesiologists and affiliated intensive care providers at Columbia University Irving Medical Center on April 15, 2020. The survey assessed 4 domains: (1) demographics and medical history, (2) community exposure to COVID-19 (eg, use of NYC subway), (3) work-related exposure to COVID-19, and (4) development of COVID-19-like symptoms after work exposure. The first 100 survey responders were invited to undergo a blood test to assess antibody status (presence of immunoglobulin M [IgM]/immunoglobulin G [IgG] specific to COVID-19). Work-related exposure was defined as any episode where the provider was not wearing adequate personal protective equipment (airborne or droplet/contact protection depending on the exposure type). Based on the clinical scenario, work exposure was categorized as high risk (eg, exposure during intubation) or low risk (eg, exposure during doffing). Two hundred and five health care providers were contacted and 105 completed the survey (51%); 91 completed the serological test. Sixty-one of the respondents (58%) reported at least 1 work-related exposure and 54% of the exposures were high risk. Among respondents reporting a work-related exposure, 16 (26.2%) reported postexposure COVID-19-like symptoms. The most frequent symptoms were myalgia (9 cases), diarrhea (8 cases), fever (7 cases), and sore throat (7 cases). COVID-19 antibodies were detected in 11 of the 91 tested respondents (12.1%), with no difference between respondents with (11.8%) or without (12.5%) a work-related exposure, including high-risk exposure. Compared with antibody-negative respondents, antibody-positive respondents were more likely to use NYC subway to commute to work and report COVID-19-like symptoms in the past 90 days. In the epicenter of the United States' pandemic and within 6-8 weeks of the COVID-19 outbreak, a small proportion of anesthesiologists and affiliated intensive care providers reported COVID-19-like symptoms after a work-related exposure and even fewer had detectable COVID-19 antibodies. The presence of COVID-19 antibodies appeared to be associated with community/environmental transmission rather than secondary to work-related exposures involving high-risk procedures.

Serum immunoglobulin E reactivity to cross-reacting panallergen components in north-eastern Poland patients pollen sensitized

Background: The presence of immunoglobulin E (IgE), which cross-reacts with allergen components, such as profilins, polcalcins, and cross-reacting carbohydrate determinants (CCD), creates a problem when selecting patients for allergen immunotherapy by using conventional methods. The aim of this study was to evaluate the prevalence of sensitization to profilins, polcalcins, and CCDs in patients with seasonal pollen allergic rhinitis. Methods: The study was performed on a group of 112 patients with seasonal pollen allergic rhinitis, ages 14 to 55 years, with sensitization to at least one seasonal allergen (IgE > 0.7 kUA/L). The presence of IgE sensitization to recombinant (r) Bet v 2, rPhl p 12, rBet v 4, rPhl p 7, and CCDs, in addition to rBet v 1, rPhl p 1, rPhl p 5, was evaluated by using a multiparameter immunoblot. Results: Among the studied patients, 64.3, 80.4, and 41.1% were sensitized to birch, timothy grass, and mugwort pollen, respectively. Sensitization to profilins rBet v 2/Phl p 12 was demonstrated in 28.6%, to polcalcins Bet v 4/Phl p 7 in 8.9%, and to CCDs in 25%. In 29.3%, serum IgE reactivity to any of the cross-reactive components could be demonstrated. Serum IgE reactivity to rBet v 2 was always accompanied by IgE reactivity to rPhl p 12, and IgE reactivity to rBet v 4 was always accompanied by IgE reactivity to rPhl p 7. Among the patients with pollinosis co-sensitized to at least two allergen sources according to extract-based diagnosis, possible false-positive results due to sensitization to cross-reactive components were detected in 17.9%. Conclusion: Evaluation of sensitization to cross-reacting components may be useful in evaluation of patients with pollen allergy who are being assessed for allergen immunotherapy to optimize the constitution of their immunotherapy vaccines.

Cryoglobulinemia and cryoglobulinemic vasculitis: etiological aspects and pathophysiological associations

The term cryoglobulinemia (CG) is used when detecting serum immunoglobulins that reversibly precipitate and form a gel at a temperature below 37 °C and dissolve when the temperature rises above 37 °C. Type I CG consists of only one isotype or a subclass of monoclonal immunoglobulins, while types II and III are classified as mixed CG (MCG) that is primarily characterized by the presence of immunoglobulins G and M. Types II and II-III MCG can result in cryoglobulinemic vasculitis (CGV) more frequently, whereas type III can lead to this condition less frequently. The presence of type I cryoglobulins is always associated with B-cell lymphoproliferative diseases. On the contrary, type II or type III MCG is more commonly associated with systemic autoimmune diseases and chronic infections. Thus, hepatitis C virus infection contributes to the development of MCG in 80–90% of cases. CGV is considered a rare disease worldwide (&lt;5 cases per 10,000 people in the general European and North American populations). Among autoimmune diseases, primary Sjögren's syndrome (Sjögren's disease), systemic lupus erythematosus, and rheumatoid arthritis are most often associated with MCG. The pathogenetic role of cryoglobulins in inducing vasculitis is associated with both leukocyte recruitment to the vessels and deposition of immune complexes, with complement system activation and microvascular damage. The pathogenesis of MCG is associated with B-cell lymphoproliferation, autoantibody production, immunoglobulin synthesis, rheumatoid factor activity and the subsequent formation of cryoprecipitated immune complexes in conjunction with ineffective cryoglobulin clearance by monocytes and/or macrophages. This review contains updated information on the epidemiology, etiology, and pathogenesis of CG, with particular emphasis on MCG and CGV.

Seroprevalence of Brucella abortus in cattle in Southern Lebanon using different diagnostic tests

Background and Aim:Brucellosis is endemic zoonotic and highly contagious bacterial disease. Recently, several brucellosis cases were reported in Lebanon, causing significant economic losses; however, no study was done so far on farms located in the southern part of the country. Thus, the aim of our study was to estimate the prevalence of Brucella abortus in South Lebanon using three different serological tests in the diagnosis of brucellosis in cattle.Materials and Methods:Seventeen farms from 14 locations in Southern Lebanon were selected. Two hundred and three bovine blood samples of different ages, and 121 milk samples collected from older than 2 years cattle were tested using different serological tests: Rose Bengal test (RBT), milk ring test (MRT), indirect enzyme-linked immunosorbent assay (I-ELISA), and confirmed with competitive ELISA (C-ELISA).Results:Results revealed that approximately 15.3% (confidence interval [CI] 95 10.3-20.2%) and 15.7% (CI 95 9.2-22.2%) of samples were positive using RBT and MRT, respectively. This percentage was significantly higher when using I-ELISA (18.3%) (CI 95 12.9-23.5%) and C-ELISA (18.7%) (CI 95 9.8-27.5%). Among used diagnostic tests, our results showed that ELISA was more accurate for the detection of brucellosis, especially since it detects the late stages of the infection, which is characterized by the presence of immunoglobulin G. The seroprevalence of brucellosis was higher among females. All positive tests were of cattle Holstein breed older than 2 years. Tyre and Jezzine cities had a higher significance in bovine brucellosis than Saida. A positive correlation between human and cattle brucellosis was found.Conclusion:Our results showed that bovine brucellosis is prevalent in southern Lebanon. Lack of research, in addition to little feedback of occurring illness or symptoms, creates a gap in helping to control the spread of the disease.

Changes in Seroprevalence of Helicobacter pylori Infection over 20 Years in Jinju, Korea, from Newborns to the Elderly.

BackgroundThe objective of this study was to examine changes in the prevalence of cytotoxic-associated gene A (CagA) positive Helicobacter pylori infection in Jinju, Korea, over the last 20 years.MethodsThree cross-sectional analyses were conducted concurrently. A total of 1,305 serum samples were collected from 1994–1995, 2004–2005, and 2014–2015, respectively. The presence of immunoglobulin (Ig) G, IgA, and IgM antibodies against H. pylori CagA protein was examined by western blotting.ResultsOverall, seropositivity for anti-CagA IgG antibody was significantly decreased from 63.2% to 42.5% over the last 20 years (P < 0.001). Anti-CagA IgG seropositivities in children and young adults aged 10–29 years decreased from 1994 (60.0%–85.0%) to 2015 (12.5%–28.9%). The age when plateau of increasing IgG seropositivity was reached in each study period shifted from the 15–19 year-old group in 1994–1995 (85.0%) to the 40–49 year-old group in 2014–2015 (82.5%). Overall seropositive rates of anti-CagA IgA and IgM antibodies did not change significantly either over the last 20 years.ConclusionH. pylori infection rate in children and young adults declined over 20 years in Jinju, probably due to improved sanitation, housing, or economy.