Changes in cytokine production during pregnancy in patients with Graves' disease

In order to investigate the role of type 1 and type 2 cytokines in the remission of Graves' disease (GD) during pregnancy, spontaneous and mitogen-stimulated production of interleukin (IL)-4, IL-6, IL-10, IL-12, interferon-γ (IFN-γ), and tumour necrosis factor-α (TNF-α) were measured by enzyme-linked immunospot assay of peripheral blood mononuclear cells from 10 pregnant women with GD, 8 healthy pregnant women, and 10 healthy nonpregnant women. Tests were performed in the first, second, and third trimesters of pregnancy and 10-17 weeks after delivery. IL-4 production was not affected greatly by normal or GD pregnancy, whereas IFN-γ production was suppressed throughout pregnancy but returned to normal levels after delivery in both controls and patients. IL-6 and TNF-α tended to be higher in GD pregnancy than normal pregnancy, especially in the second and third trimesters. Controls had raised IL-10 in the first trimester with a return to normal levels by the third trimester, whereas patients had raised levels throughout pregnancy. IL-12 levels were suppressed to a greater extent in control than Graves' pregnancy, especially during the second and third trimesters. Ratios of IL10:IL12 in phytohemaglutinin (PHA)-stimulated cultures were much lower in GD than normal pregnancy and cross-regulation of IL-10 and IL-12 may be deficient in GD.published_or_final_versio

Lowered Immune Cell Function in Liver Recipients Recovered From Posttransplant Lymphoproliferative Disease Who Developed Graft Tolerance

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Chronic benign neutropenia among Chinese children

Objective. To delineate the clinical behaviour of chronic benign neutropenia in Chinese children in Hong Kong. Design. Retrospective study. Setting. University teaching hospital, Hong Kong. Patients. All infants and children with absolute neutrophil count of 1.5 × 109 /L or lower for more than 3 months. Main outcome measures. Development of significant infection, and achievement of remission. Results. Twenty-four children with chronic benign neutropenia were identified between 1992 and 2001. Their median age of diagnosis was 9 months. The mean (standard deviation) initial absolute neutrophil count was 0.28 × 109 /L (0.24 × 109 /L). Twenty-three patients presented with infection. Of the 19 patients tested, four (21%) were positive for anti-neutrophil antibodies. Bone marrow examination was performed in 17 patients: nine had normal results, but six showed evidence of peripheral consumption, one showed late maturation arrest at band stage, and one showed phagocytosis of myeloid cells by histiocytes. The overall hospitalised infection rate was 51.6 episodes per 1000 patient-months. Ten percent of cases were considered 'significant' infections and required hospital admission with either surgical intervention or intravenous therapy (antibiotics or fluid replacement). In the first year of diagnosis, more than 80% of patients had their lowest absolute neutrophil count (mean, 0.16 × 109 /L; standard deviation, 0.11 × 109 /L). Granulocyte-colony stimulating factor was used to treat three patients and induced transient elevation of absolute neutrophil count in all three. The projected remission rate was 55.4% at 3 years. Even for those with persistent disease, there was significant recovery in absolute neutrophil count to a mean of 0.5 × 109 /L (P<0.01). Conclusions. Patients with chronic benign neutropenia experienced a relatively benign clinical course regardless of their remission status. Only a small proportion of patients developed significant infections. A multi-centre prospective study may help identify predictive factors of remission.published_or_final_versio

The 23-valent polysaccharide pneumococcal vaccination is not useful in BMT patients at risk of pneumococcal bacteremic sepsis

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Assessment of SARS-CoV-2 Immunity in Convalescent Children and Adolescents

Persistence of protective immunity for SARS-CoV-2 is important against reinfection. Knowledge on SARS-CoV-2 immunity in pediatric patients is currently lacking. We opted to assess the SARS-CoV-2 adaptive immunity in recovered children and adolescents, addressing the pediatrics specific immunity towards COVID-19. Two independent assays were performed to investigate humoral and cellular immunological memory in pediatric convalescent COVID-19 patients. Specifically, RBD IgG, CD4+, and CD8+ T cell responses were identified and quantified in recovered children and adolescents. SARS-CoV-2-specific RBD IgG detected in recovered patients had a half-life of 121.6 days and estimated duration of 7.9 months compared with baseline levels in controls. The specific T cell response was shown to be independent of days after diagnosis. Both CD4+ and CD8+ T cells showed robust responses not only to spike (S) peptides (a main target of vaccine platforms) but were also similarly activated when stimulated by membrane (M) and nuclear (N) peptides. Importantly, we found the differences in the adaptive responses were correlated with the age of the recovered patients. The CD4+ T cell response to SARS-CoV-2 S peptide in children aged <12 years correlated with higher SARS-CoV-2 RBD IgG levels, suggesting the importance of a T cell-dependent humoral response in younger children under 12 years. Both cellular and humoral immunity against SARS-CoV-2 infections can be induced in pediatric patients. Our important findings provide fundamental knowledge on the immune memory responses to SARS-CoV-2 in recovered pediatric patients

Alpha-1 antitrypsin gene polymorphism in Chronic Obstructive Pulmonary Disease (COPD)

Alpha-1-antitrypsin (AAT) plays an important role in the pathogenesis of emphysema, the pathological lesion underlying the majority of the manifestations of Chronic Obstructive Pulmonary Disease (COPD). In this study we tested the hypothesis that common AAT polymorphisms influence the risk of developing COPDs. We investigated PiM1 (Ala213Val), PiM2 (Arg101His), PiM3 (Glu376Asp), PiS (Glu264Val) and PiZ (Glu342Lys) SERPINA1 alleles in 100 COPD patients and 200 healthy controls. No significant differences were observed in allele frequencies between COPD patients and controls, neither did haplotype analysis show significant differences between the two groups. A cross-sectional study revealed no significant relationship between common SERPINA1 polymorphisms (PiM1, PiM2, PiM3) and the emphysematous type of COPD. In addition, FEV1 annual decline, determined during a two-year follow up period, revealed no difference among carriers of the tested polymorphisms