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Summary The association between immune dysfunction and the development of autoimmune pathology in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is not clear. The frequency and phenotype of regulatory T cells, as well as the presence of autoantibodies, were evaluated in a paediatric cohort of HIV-infected patients without clinical evidence of autoimmune disease. Lower absolute counts but higher percentages of total CD4+ forkhead box protein 3 (FoxP3)+ T cells were recorded in children with severe immunosuppression than in those without evidence of immunosuppression. The frequencies of classical CD4+CD25+FoxP3+ regulatory T cells were not altered, whereas CD4+FoxP3+CD25- T cells were found increased significantly in patients with severe immunosuppression. Like classical regulatory T cells, CD4+FoxP3+CD25- T cells display higher cytotoxic T-lymphocyte antigen 4 (CTLA-4) but lower CD127 expression compared with CD4+FoxP3-CD25+ T cells. An improvement in CD4+ T cell counts, along with a decrease in viral load, was associated with a decrease in CD4+FoxP3+CD25- T cells. The majority of the patients with severe immunosuppression were positive for at least one out of seven autoantibodies tested and displayed hypergammaglobulinaemia. Conversely, HIV-infected children without evidence of immunosuppression had lower levels of autoantibodies and total immunoglobulins. A decline in CD4+FoxP3+ T cell numbers or a variation in their phenotype may induce a raise in antigen exposure with polyclonal B cell activation, probably contributing to the generation of autoantibodies in the absence of clinical autoimmune disease. [ABSTRACT FROM AUTHOR]

The intercellular adhesion molecule-1 (ICAM-1) is a cytokine-induced glycoprotein involved in the recruitment of cells into tissues undergoing inflammatory responses. The aim of this study was to compare the levels of soluble ICAM-1 (s-ICAM-1) in children with juvenile chronic arthritis (JCA) and systemic lupus erythematosus (SLE) and to evaluate the usefulness of this molecule as marker of disease activity. Levels of s-ICAM-1 were measured in sera using a monoclonal antibody sandwich enzyme-linked immunoassay. Serum levels (mean ± SD) of s-ICAM-1 in 37 children with JCA, 18 patients suffering from SLE and 25 healthy controls were 609 ± 184, 513 ± 139 and 210 ± 95 ng/ml, respectively. A significant difference could be demonstrated between the levels of s-ICAM-1 in sera from each disease, as a group, and those of healthy controls. Higher levels of s-ICAM-1 were recorded in JCA patients with systemic features and patients who had polyarthritis than in children who were pauciarticular. A positive correlation was observed between s-ICAM-1 levels and disease activity score in SLE patients. Moreover, s-ICAM-1 levels closely followed clinical conditions in five children with SLE during follow-up. The data show that s-ICAM-1 levels are increased in children suffering from connective tissue diseases and reflect disease status or activity, suggesting the usefulness of this molecule in the follow-up of these diseases. [ABSTRACT FROM AUTHOR]

Background: The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain., Methods: We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events., Results: Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded., Conclusion: In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted., Trial Registration: ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Dermatitis is the most common adverse event during treatment with benznidazole in chronic Chagas disease and is probably mediated by T cells. A set of molecules representative of the different type IV hypersensitivity reactions was evaluated in the circulation and skin biopsies of Trypanosoma cruzi-infected subjects presenting dermatitis during benznidazole administration. Through cytometric bead assays and enzyme-linked immunosorbent assay capture techniques, the serum levels of cytokines, chemokines, proapoptotic molecules, and mediators of the activation and migration of eosinophils and T cells were measured in subjects infected with Trypanosoma cruzi who exhibited skin adverse events ( n  = 22) and compared with those without adverse events ( n  = 37) during benznidazole therapy. Serum levels of interleukin- 5 (IL-5), soluble Fas cell surface death receptor ligand (FAS-L), and interferon γ-induced protein (IP-10) significantly increased at 7 to 30 days posttreatment with benznidazole and decreased thereafter in subjects with dermatitis but not in those without dermatitis. Circulating eotaxin levels were lower in subjects with dermatitis than in those without. Two patterns emerged in the skin biopsies: a T helper 1/T cytotoxic profile and a T helper 2/T cytotoxic profile with the presence of CD4 + and CD8 + T cells. Increased low-density lipoprotein (LDL), glutamic-oxaloacetic transaminase (GOT), uremia, and T cell activation emerged as risk factors for the development of dermatitis during benznidazole administration. These results support a delayed-type hypersensitivity reaction to benznidazole, involving CD4 + and CD8 + T cells and eosinophils, and a mixed cytokine profile. This study provides new insights for better management of adverse drug reactions to benznidazole. IMPORTANCE This study identified the risk factors for the development of adverse reactions to benznidazole and identified a set molecule to monitor the appearance of these reactions. This knowledge might improve the safety of benznidazole administration.

Specific antibodies are produced after infection by SARS-CoV2. Currently, the understanding of antibody responses following infection with SARS-CoV-2 is limited including the magnitude, duration of responses and correlates of protective immunity following infection. Here we intended to characterize humoral immune response in a cohort of 55 hospitalized patients for COVID-19 and its relationship with different demographic and clinical parameters. The ELFA assay VIDAS® SARS-Cov-2 (Biomerieux) measured IgG/IgM antibodies. Their concentration over time was evaluated with a fixed effects generalized linear model. All patients seroconverted IgM and IgG, at day 10 and 10.5 respectively, showing a majority synchronous pattern; IgM alone would not be useful as a marker of acute response. Clinical sensitivity was: week 1, 30%, weeks 2 and 3, 72%, 4: 91% and 8: 96%. IgG seropositivity was sustained in patients up to 180 days (last time point measured), in contrast, IgM response was short-lived (91days) in 90.9% of patients. Longer term follow-up is needed to determine the duration of IgG responses. We observed a higher level of IgM in patients > 56 years, and in men compared to women. In chronic obstructive pulmonary disease patients, the IgM response is increased, while in immunocompromised and interstitial lung disease patients, IgM and IgG were lower, respectively. Those patients who required critical care, mechanical ventilation and those who died did not present significant differences in the magnitude of humoral response compared to those who had a less severe course. The methodology used adequately reflects the kinetics of antibodies.

Introduction: Mycoplasma pneumoniae (Mypn) infection could be occurring at an earlier age due to social pheno mena such as attending daycare centers more frequently and earlier than decades ago., Objective: to estimate the prevalence of anti-Mypn antibodies in children aged 0-12 years, and to explore whether age, attendance to daycare center/school, overcrowding or the presence of children aged below 12 years in the households increase the risk of seropositivity., Patients and Method: Cross-sectional stu dy including healthy children aged 0-12 years which required blood draws for routine laboratory tests. In all cases, the aforementioned variables were recorded and anti-Mypn IgG was determined by enzyme immunoassay. The association between predictors and seropositivity was assessed in a logistic regression model., Results: We included 232 patients (average age 56.4 ± 40.0 months). 56.9% attended a daycare center/school, 63.8% co-habited with children under 12 years old, and 15.9% lived in overcrowded households. The prevalence of anti-Mypn antibodies was 14.6%. There were no significant differences between seropositive and seronegative children regarding age (63.1 ± 40.7 vs. 55.4 ± 41.3 months), school/day-care attendance (64.7% vs. 55.5%), overcrowding (14.7% vs. 14.9%), or co-habiting with children (64.7% vs. 63.6%). Age was not an independent predictor of seropositivity in the multivariate model., Conclusion: The prevalence of anti-Mypn antibodies in children was 14.6% and age was not a predictor of seropositivity.

To evaluate the levels of recent thymic emigrant (RTE) CD4 + T cells in HIV-infected children and to explore the associations among their frequency, antiretroviral treatment (ART) adherence, and CD4 + T cell restoration. The group evaluated comprised 85 HIV-infected patients classified as subjects with moderate or severe immunosuppression or as those with no evidence of immunosuppression. To evaluate the association between the frequency of RTE CD4 + T cells and ART adherence, 23 of the 85 patients were evaluated at two different time points during a one-year follow-up period. Children with severe immunosuppression had lower frequencies of RTE CD4 + T cells compared with children without evidence of immunosuppression (P < .001). The frequency of RTE CD4 + T cells in children with a high rate of adherence was significantly higher (P < .05) than that observed among those with suboptimal adherence. The latter group presented with infectious intercurrences on admission that decreased after initiation of treatment along with improved CD4 + and RTE naïve CD4 + T cells counts. The adequate ART adherence is essential for immune reconstitution, which might be reflected by the levels of RTE CD4 + T cells., (© 2019 The Scandinavian Foundation for Immunology.)

Different primary immunodeficiencies present increased levels of IgE and cutaneous infections of viral etiology. We report a case of a 2 y, 8 m old boy with combined immunodeficiency, dermatitis and disseminated molluscum contagiosum. The patient presented high titers of IgE, eosinophilia and pronounced TCD8 lymphopenia. Impaired proliferation assays and abnormal antibody response to vaccination were found. Normal results of ZAP-70 protein, NK function, and HLA I levels, to test quantitatives and functional defects of cytotoxic cells, lead us to suspect a mutation in DOCK8 gene. Positive result in molecular study together with clinical and immunology features in the patient confirmed the diagnosis of this new immunodeficiency, being to the authors' knowledge the first case recorded in a paediatric hospital in our country.

Human immunodeficiency virus infection causes a severe depletion of TCD4+ lymphocytes and a sustained immune activation state, hallmarks findings that led to numerical and phenotypic changes in the TCD4+ subsets. Highly active anti-retroviral therapy has substantially modified the course of HIV infection. Correct adherence to the treatment results in a decrease in viral load at undetectable levels and a significant increase in the number of peripheral T cell lymphocytes. In the present study association between changes in T cell subsets and treatment adherence was evaluated in 28 HIV (+) infected children, before and after 9 months on average, from starting anti-retroviral therapy. The group of 18 patients with good adherence, above 95%, showed a significant increase in CD4+CD45RA+CD62L+ naive cells percentual levels and a decrease in the CD4+CD45RA-CD62L+ central memory subset, between the two points of the follow-up period. Conversely, 10 children with failure in the adherence did not show significant differences in the percentual levels of both subsets. Improvement in the percentage of adherence among paediatric population, optimizing antiretroviral treatment, allows a quick and significant reduction of viral replication. This feature is associated with the progressive reconstitution of the immune system.

Thrombocytopenia is a common hematologic finding in patients infected with the human immunodeficiency virus. Multiple mechanisms may contribute to the development of chronic thrombocytopenia as immune-mediated platelet destruction, enhanced platelet splenic sequestration and impaired platelet production. Acute thrombocytopenia is frequently associated with coexisting disorders. In this study, the prevalence of thrombocytopenia was evaluated in a cohort of HIV infected children analyzing the clinical features and the association with the immunological and virological status of the disease in a 14 year-follow-up period. Thrombocytopenia prevalence was of 8.5% (29 out 339 children evaluated). Chronic and acute thrombocytopenia was observed in 22 and 7 children respectively. The percentages of CD4+ T cells were variable and not related with the presence of thrombocytopenia. Thrombocytopenic patients showed viral load levels significantly increased; being the thrombocytopenia the initial clinical manifestation of HIV infection in 10 out 29 children. Mild chronic thrombocytopenia bleeding found in 23% of children evaluated was not correlated with the immunologic status of the disease. In contrast, the severity of acute thrombocytopenia depended on the evolution of associated clinical conditions. Constant viral activity and failure in the use of antiretroviral agents might induce the development of thrombocytopenia in HIV-infected children.

Introduction: Although Mycoplasma pneumoniae is usually assumed as an infection mainly prevalent in school aged children and adolescents, there is evidence supporting that it may occur at younger ages. This could be related to social conditions, like crowding and day care center/school attendance more frequently and at younger ages than two decades ago. We estimated the prevalence of antibodies anti- Mycoplasma pneumoniae in children aged under 12 years. We also evaluated its association with age, day care center/school attendance, crowding or other children in the household., Population and Methods: This cross-sectional study included children aged under 12 years that required blood sampling for surgery. Those with acute infections, chronic diseases or known immunological disorders were excluded. In all cases predictors were recorded, and IgG anti-Mycoplasma pneumoniae determined by enzimoimmunoassay. Association between predictors and seropositivity was evaluated by logistic regression., Results: We included 355 children, aged 4.8 +/- 3.1 years. 57.6% attended to day care center/school, crowding was present in 27.3% and 70.1% had other children in the household. IgG antibodies anti-Mycoplasma pneumoniae were present in 12.4%. Seropositives were older than seronegatives (7.1 +/- 3.15 years vs. 4.4 +/- 3.06 years, p < 0.0001). After controlling by confounders, age remains as an independent predictor of seropositivity (OR: 1.19, CI 95%: 1.043-1.362)., Conclusions: Seroprevalence of Mycoplasma pneumoniae IgG antibodies in children aged under 12 years was 12.4%. Age is an independent predictor of seropositivity.

Cryptosporydium parvum is an intracellular parasite that infects gastrointestinal epithelium and produces diarrhea that is self-limited in immunocompetent persons but potentially life-threatening in immunocompromised, especially those with the acquired immunodeficiency syndrome (AIDS). C. parvum enteric infection's incidence in a pediatric HIV/AIDS cohort, during a 6 years period, was studied. Clinical and immunologic characteristics of the dual infection were also recorded. Highly active antiretroviral therapy (HAART) was started or continued by all the patients during follow-up. Azithromicyn was used as antiparasitic drug. Cryptosporidiosis incidence was 13.7%; 33 out 240 children showed chronic diarrhea lasting 14 days at least, or recurrent, without dehydration and electrolytic disturbance. Peripheral blood T CD4+ percentage levels of the patients were variable and without relationship with C. parvum presence. Viral load levels in 31 out 33 patients were over cut-off at the enteric episode time. Mild or moderate eosinophilia were recorded in 23% of the patients and other intestinal parasites were present in 11 children. When the number of enteric episodes were compared with the clinical and immunological patient's status, not significant differences were recorded. HAART is the best treatment to improve immune function in HIV patients avoiding potentially fatal complications that accompany acute diarrhea during concomitant infection with C. parvum.

The ability of leukocytes to leave the circulation and migrate into tissues is a critical feature of the immune response. L-selectin (CD62L), the leukocyte selectin, mediates the binding of lymphocytes to high endothelial venules of peripheral lymph nodes and is also involved in lymphocyte, neutrophil and monocyte attachment to vascular endothelium at sites of inflammation. In this study L-selectin expression on peripheral T cells and neutrophils was evaluated in 25 HIV infected children, who had not received antiretroviral therapy, and 25 healthy controls. The expression level of L-selectin on T cells was also evaluated in 10 out 25 patients after 6 months of antiretroviral therapy. L-selectin expression on CD3+, CD4+ and CD8+ T cells were significantly lower in HIV infected children than in the control group. The percentage of neutrophils expressing CD62L was significantly reduced in patients with severe immunologic suppression. A positive correlation between the number of CD4+ T cells and the percentage of neutrophils CD62L+ was found. L-selectin expression on both CD4+ and CD8+ T cells did not significantly vary after 6 months of treatment. Altered leukocyte functions such as migration and homing resulting from reduced expression of CD62L may be an important contributor of the progressive dysfunction of the immune system in HIV infected children.

L-selectin is an adhesion molecule that is responsible for the initial attachment of leukocytes to endothelium. After leukocyte activation L-selectin is endoproteolytically released from the cell surface. In order to analyze the relationship between soluble L-selectin (sL-selectin) and parameters of immune activation and disease progression, 51 HIV infected children and 15 healthy controls were studied. Serum L-selectin concentrations were significantly higher in HIV infected children than in the control group. Levels of sL-selectin were higher in HIV infected patients with severe immunologic suppression than in those with moderate or no evidence of suppression. A positive correlation between sL-selectin levels and LTCD8 counts, sL-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) and immunogobulin A (IgA) levels was detected. On the contrary sL-selectin concentration did not correlate with plasmatic viral load. The correlation with parameters of immune activation may implicate involvement of sL-selectin in the immunopathogenesis of HIV infection.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane bound molecule that is involved in cell to cell adhesive interactions within the immune system. The aim of this study was to measure the concentrations of soluble ICAM-1 (s-ICAM-1) in 25 HIV-1 infected pediatric patients. We compared s-ICAM-1 values to parameters of immune activation--such as IgA and beta 2 microglobulin (beta 2 m) and viral replication such as adenosine deaminase (ADA). s-ICAM-1 levels were found to be significantly increased in HIV-1 infected children when compared with healthy controls. Levels of s-ICAM-1 were higher in patients with severe forms of HIV-1 infection in comparison with those with a mild form of the disease or non symptomatic infection. No differences in titers of s-ICAM-1 were recorded between seroreverters and healthy controls. A positive correlation between levels of s-ICAM-1 and IgA, beta 2 m or ADA concentrations was detected. Similarly, there was statistically significant correlation between levels of IgA, beta 2 m or ADA. In conclusion, increased s-ICAM-1 levels in HIV-1 pediatric patients appeared to be another important feature among the immune disturbances triggered by HIV-1 infection. s-ICAM-1 might be involved in the development of the immunologic dysfunction during the progression of the disease.

The aim of this retrospective study, which included 103 children born to human immunodeficiency virus type 1 (HIV-1)- infected mothers, is to initiate a database on HIV-infected children, which has to date been unavailable in Argentina. All HIV-1 seropositive children admitted to the Pedro de Elizalde Children's Hospital in Buenos Aires from March 1, 1987, to December 31, 1992, were enrolled in this study. The number of patients enrolled dramatically increased each year during the period of study. Of the 60 infected children, 22 (36.66%) have died with a clinical diagnosis of HIV-1 infection; in 10 of those children HIV infection was also confirmed by P24 antigenemia and/or polymerase chain reaction (PCR): 20 qualified for the Centers for Disease Control and Prevention (CDC) P2D class (P2D1 = 7, P2D2 = 10, P2D3 = 3), 1 for P2C, and 1 for P2A, whose cause of death was pneumonia. The mean age of death was 14.8 months, 18 (82%) died before 18 months. When immunoglobulin G (IgG), IgM, and IgA levels were determined according to age and clinical status, significant differences (P < 0.005) were observed when both asymptomatic and symptomatic infected children (P1, P2) were compared with noninfected children (P3). A significant difference was also obtained between those children who qualified for P2 classification prior to 12 months of age who died early (at or prior to 25 months) and those who reached stage P2 after 12 months of age and have survived to date (X2 = 24.73, p < 0.0001; RR = 5.83, 2.52 < RR < 13.49).