Serum immunoglobulins in children perinatally exposed to human immunodeficiency virus

OBJECTIVE: Hypergammaglobulinemia is an early manifestation of perinatal HIV infection. Our objective was to analyze the differences in serum immunoglobulin levels between infected and seroreverting children and their association with clinical outcome. METHODS: We carried out a historical prospective study with 107 infected and 90 seroreverting children. We compared the IgA, IgG, and IgM levels between infected and seroreverting patients within the first 18 months of life; IgA, IgG, and IgM as surrogate markers of infection; and IgA, IgG, and IgM levels within the first 5 years in infected children, according to clinical outcome. The Mann-Whitney test was used for comparison between groups. Surrogate markers were assessed according to sensitivity, specificity, positive and negative predictive values, and Youden's index. RESULTS: Infected children, when compared to seroreverters, showed significantly higher levels of IgM between the 1st and 5th trimesters; IgA and IgG between the 2nd and 6th trimesters (P less than or equal to 0.05). Levels of IgA greater than or equal to 90 mg/dl in the 2nd trimester and IgG greater than or equal to 1,700 mg/dl or 1,200 mg/dl in the 2nd and 3rd trimesters were associated with HIV infection, with Youden's indexes of 0.97, 0.92, and 0.93, respectively. Infected children in the B and C categories, compared to those in the N and A, showed higher levels of IgM between the 2nd and 4th years, and IgA between the 3rd and 5th year (P > 0.05). CONCLUSIONS: The temporal progression of IgA, IgG, and IgM levels showed an early and intense stimulation to the synthesis of immunoglobulin in infected children. Clinical and epidemiological indicators showed that such levels may be surrogate markers of infection. Higher IgM and IgA levels between the 2nd and 5th years in more severely infected children suggest a dysfunction in immune regulation secondary to persistent antigenic stimulation.OBJETIVO: a hipergamaglobulinemia é uma manifestação precoce da infecção perinatal por HIV. O objetivo foi analisar as diferenças nos níveis séricos de imunoglobulinas entre crianças infectadas e sororreversoras, e sua associação com a evolução clínica. MÉTODOS: Em um estudo prospectivo histórico, avaliaram-se 107 crianças infectadas e 90 sororreversoras. Compararam-se: IgA, IgG e IgM entre infectados e sororreversores nos primeiros 18 meses de vida; IgA, IgG e IgM como marcadores indiretos de infecção; IgA, IgG e IgM nos 5 primeiros anos em infectados, de acordo com a evolução clínica. Utilizou-se o teste de Mann-Whitney para a comparação entre grupos. Na avaliação de marcadores indiretos, analisaram-se Sensibilidade, Especificidade, Valores Preditivos Positivo e Negativo, e índice J. RESULTADOS: Infectados, em relação a sororreversores, apresentaram níveis significativamente superiores de IgM, do 1o ao 5o trimestre; IgA e IgG, do 2o ao 6o trimestre (P 90 mg/dl no 2o trimestre e IgG > 1.700 mg/dl ou 1.200 mg/dl no 2o e 3o trimestres associaram-se à infecção por HIV com índices J de 0,97, 0,92 e 0,93, respectivamente. Crianças infectadas nas categorias B e C, comparadas àquelas nas categorias N e A, apresentaram níveis superiores de IgM, do 2o ao 4o ano e IgA, do 3o ao 5o ano (P £.0,05). CONCLUSÕES: A evolução temporal dos níveis de IgA, IgG e IgM demonstra um estímulo intenso e precoce à síntese de imunoglobulinas em infectados. Indicadores clínico-epidemiológicos demonstram que tais níveis podem ser marcadores indiretos de infecção. Níveis superiores de IgM e IgA do 2o ao 5o ano em crianças infectadas com maior gravidade sugerem disfunção na regulação imune secundária ao estímulo antigênico persistente.20921

Clearance of Persistent SARS-CoV-2 RNA Detection in a NFκB-Deficient Patient in Association with the Ingestion of Human Breast Milk: A Case Report

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infection in immunodeficient patients

Ataxia-telangiectasia : epidemiological survey in latin america

Ataxia-telangiectasia (AT) is a rare neurodegenerative disorder characterized by ataxia, telangiectasia, and immunodeficiency. We aimed to evaluate the multisystem involvement in AT by describing clinical features and outcomes of Latin American (LA) patients. cross-sectional and multicenter study. Referral centers from all over LA filled in a questionnaire with clinical and laboratory data based on patients’ records. 228 patients from 10 LA countries were evaluated. Mean ages at the time of symptom onset and diagnosis were 1.63±1.09 and 5.66±3.48 years, respectively. The most common immunodeficiency was IgA deficiency (60.8%), followed by IgG deficiency (28.6%). IgA and IgM showed a tendency to decrease as the patient grew older (p=0.001 and 0.048). IgA deficiency was associated with recurrent airway infections (p=0.038). 120 (79,5%) patients presented with low CD3+CD4+ count and 115 (92%) with low CD19+ count. Regarding nutritional status, as patients grow older there is an increase in severe thinness (p=0.016). Median survival was 23 years and Kaplan-Meier 20-year-survival rate was 52,6%. IgG deficiency and female gender were associated with a decrease in estimated survival function (p=0.02 and 0.049). There is a high prevalence of laboratory immunologic abnormalities and recurrent infections in AT patients. Knowledge of specific regional characteristics and variables which can be related with survival allows for suitable patient follow-up and may increase quality of life143

Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome

Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. Methods: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. Results: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4−CD8−) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. Conclusion:: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome