Idiopathic thrombocytopenic purpura as initial manifestation of juvenile systemic lupus erythematosus

Patients with Idiopathic Thrombocytopenic Purpura (ITP) present a high trend to develop Systemic Lupus Erythematosus (SLE), especially those with chronic presentation. Some authors observed that female gender, older patients and familial history of autoimmune disease in patients with Idiopathic Thrombocytopenic Purpura are factors that lead to increased susceptibility for the development of Systemic Lupus Erythematosus. Based on these facts, we decided to study 5 children with chronic Idiopathic Thrombocytopenic Purpura and late Systemic Lupus Erythematosus. In this paper, we describe the clinical and laboratorial features of 5 female children with Idiopathic Thrombocytopenic Purpura that later developed Systemic Lupus Erythematosus. All patients were girls, 3 Caucasian, with Idiopathic Thrombocytopenic Purpura onset age ranged between 6 years and 3 months and 12 years and 1 month (mean - 9 years and 2 months). The age at Systemic Lupus Erythematosus diagnosis ranged between 8 years and 13 years and 8 months (mean - 10 years and 10 months). Though, the gap between Idiopathic Thrombocytopenic Purpura and Systemic Lupus Erythematosus diagnosis ranged between 11 months and 2 years and 9 months (mean - 1 year and 10 months). All patients presented chronic Idiopathic Thrombocytopenic Purpura (thrombocytopenia lasts longer than 6 months). The Systemic Lupus Erythematosus classification criteria were (in decreasing frequency): malar erythema and positivity of ANA in 5 patients; arthritis, hematological (thrombocytopenia) and immunological alterations (positivity of anti-DNA) in 4 patients; photosensitivity and positivity of anti-cardiolipin in 3 patients. Other manifestations included oral ulcers, renal involvement, leukopenia and auto-immune hemolytic anemia, serositis (pericarditis), neurological involvement and positivity of anti-Sm antibody. We would like to emphasize this form of presentation of Systemic Lupus Erythematosus, in which the Idiopathic Thrombocytopenic Purpura was the first manifestation and that the auto-antibody determination in every children with chronic form of this disease is very important.Os pacientes com púrpura trombocitopênica imunológica apresentam risco aumentado para desenvolver lúpus eritematoso sistêmico, principalmente quando a doença evolui de forma crônica. Alguns autores observaram que o sexo feminino, a idade mais avançada, a história familiar para lúpus eritematoso sistêmico podem ser fatores indicadores de maior risco para desenvolver lúpus em pacientes com púrpura trombocitopênica imunológica. Com base nestes fatos, resolvemos estudar cinco crianças nas quais a púrpura trombocitopênica imunológica foi o primeiro sintoma do lúpus eritematoso sistêmico. Neste artigo descrevemos as características clínicas e laboratoriais de cinco crianças com púrpura trombocitopênica imunológica que desenvolveram lúpus eritematoso sistêmico juvenil. Todas as crianças eram do sexo feminino - três caucasóides e duas pardas, com idade do início das manifestações de PTI variando entre 6 anos e 3 meses a 12 anos e 1 mês (média de 9 anos e 2 meses). A idade do diagnóstico de LESJ variou de 8 a 13 anos e 8 meses (média de 10 anos e 10 meses). Portanto, o intervalo de tempo entre o quadro de PTI e o diagnóstico de LESJ foi de 11 meses a 2 anos e 9meses (média de 1 ano e 10 meses). Todas as crianças apresentavam quadro de PTI crônica (plaquetopenia por mais de 6 meses). Os critérios de classificação para LESJ foram, em ordem de freqüência: rash malar e FAN positivo em 5 pacientes; artrite, alterações hematológica (plaquetopenia) e imunológica (anticorpo anti-DNA nativo) em 4; fotossensibilidade e ACL positivo em 3. Outras manifestações associadas foram úlceras orais, alterações renal e hematológica (leucopenia e AHAI com TCD positivo); serosite (pericardite), acometimento neurológico e alteração imunológica (anticorpo anti-Sm). Gostaríamos de alertar para esta forma de apresentação do lúpus eritematoso sistêmico em que o primeiro sintoma foi a púrpura trombocitopênica imunológica e salientar a importância da determinação de auto-anticorpos para lúpus eritematoso sistêmico nas crianças com a forma crônica desta patologia.UNIFESP-EPMUNIFESP, EPMSciEL

Results from transcranial Doppler examination on children and adolescents with sickle cell disease and correlation between the time-averaged maximum mean velocity and hematological characteristics: a cross-sectional analytical study

CONTEXT AND OBJECTIVE: Transcranial Doppler (TCD) detects stroke risk among children with sickle cell anemia (SCA). Our aim was to evaluate TCD findings in patients with different sickle cell disease (SCD) genotypes and correlate the time-averaged maximum mean (TAMM) velocity with hematological characteristics. DESIGN AND SETTING: Cross-sectional analytical study in the Pediatric Hematology sector, Universidade Federal de São Paulo. METHODS: 85 SCD patients of both sexes, aged 2-18 years, were evaluated, divided into: group I (62 patients with SCA/Sß0 thalassemia); and group II (23 patients with SC hemoglobinopathy/Sß+ thalassemia). TCD was performed and reviewed by a single investigator using Doppler ultrasonography with a 2 MHz transducer, in accordance with the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. The hematological parameters evaluated were: hematocrit, hemoglobin, reticulocytes, leukocytes, platelets and fetal hemoglobin. Univariate analysis was performed and Pearson's coefficient was calculated for hematological parameters and TAMM velocities (P < 0.05). RESULTS: TAMM velocities were 137 ± 28 and 103 ± 19 cm/s in groups I and II, respectively, and correlated negatively with hematocrit and hemoglobin in group I. There was one abnormal result (1.6%) and five conditional results (8.1%) in group I. All results were normal in group II. Middle cerebral arteries were the only vessels affected. CONCLUSION: There was a low prevalence of abnormal Doppler results in patients with sickle-cell disease. Time-average maximum mean velocity was significantly different between the genotypes and correlated with hematological characteristics

CD22 Regulates Adaptive and Innate Immune Responses of B Cells

B cells sense microenvironments through the B cell receptor (BCR) and Toll-like receptors (TLRs). While signals from BCR and TLRs synergize to distinguish self from nonself, inappropriate regulation can result in development of autoimmune disease. Here we show that CD22, an inhibitory co-receptor of BCR, also negatively regulates TLR signaling in B cells. CD22-deficient (Cd22–/–) B cells exhibit hyperactivation in response to ligands of TLRs 3, 4 and 9. Evidence suggests that this results from impaired induction of suppressors of cytokine signaling 1 and 3, well-known suppressors of TLR signaling. Antibody-mediated sequestration of CD22 on wild-type (WT) B cells augments proliferation by TLR ligands. Conversely, expression of CD22 in a Cd22–/– B cell line blunts responses to TLR ligands. We also show that lipopolysaccharide-induced transcription by nuclear factor-κB is inhibited by ectopic expression of CD22 in a TLR4 reporter cell line. Taken together, these results suggest that negative regulation of TLR signaling is an intrinsic property of CD22. Since TLRs and BCR activate B cells through different signaling pathways, and are differentially localized in B cells, CD22 exhibits a broader regulation of receptors that mediate adaptive and innate immune responses of B cells than previously recognized