Cell activation, PD-1 expression and in vitro cytokine production in patients with juvenile systemic lupus erythematosus.

BACKGROUND: Juvenile systemic lupus erythematosus (jSLE) is known to be more severe and with a higher frequency of renal and central nervous system impairment when compared to systemic lupus erythematosus in adults. The study of immunological characteristics of jSLE patients might help to envisage better treatment strategies to reduce the burden of the disease. OBJECTIVE: To characterize peripheral lymphocytes, assessing activation markers, and PD-1 expression on T cells; to evaluate in vitro cytokine expression upon stimulation in jSLE patients and age-matched controls. METHODOLOGY: Eighteen jSLE patients on low disease activity and 25 matched healthy adolescents were evaluated for immune activation and PD-1 expression on peripheral blood lymphocytes by flow cytometry. Twenty-one cytokines were assessed by X-MAP technology after in vitro stimulation of peripheral blood with phytohemagglutinin. RESULTS: jSLE patients had lower numbers of CD4 T, CD8 T, B, and NK cells; higher central memory CD8 T cell percentages were noted in jSLE adolescents in comparison with controls (p = 0.014). B cells subsets showed a higher percentage of exhausted memory subset than controls (p = 0.014). The expression of PD-1 on CD4 T and CD8 T cells did not show relevant changes in jSLE adolescents. After stimulation of peripheral blood, cell supernatant of jSLE patients showed a trend to lower concentrations of IL-10 (p=0.080) and higher concentrations of IL-23 (p = 0.063) than controls. CONCLUSIONS: jSLE patients on low disease activity maintain lymphopenia of all subsets, with a B cell profile of exhaustion. Upon in vitro stimulation, peripheral blood cell supernatant showed a shift to IL-23, suggesting a role of inhibitors of this cytokine as another potential therapeutic target for those patients.

Adequate tetanus but poor diphtheria and pertussis response to a Tdap booster in adolescents with juvenile systemic lupus erythematosus.

BACKGROUND: Reports on vaccine responses in immunocompromised patients, such as juvenile systemic lupus erythematosus (jSLE), have shown highly variable results. OBJECTIVE: To compare the immune response and safety after a Tdap booster in 26 jSLE patients and 26 matched healthy adolescents.Methodology: Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole cell pertussis and supernatants were assessed for cytokines by xMAP. RESULTS: Both groups showed a similar frequency of adverse events. There was no evidence of disease reactivation after Tdap booster in the jSLE cohort. Both groups showed a significant increase in antibody titers for all three antigens on D14 and D28 (p < 0.001). jSLE patients had a significantly lower increase in diphtheria titers than the control group (p = 0.007). jSLE patients had a distinct titer increase of tetanus and pertussis antibodies when compared to controls (p = 0.004 and p < 0.001, respectively). There was a lower frequency of pertussis seroconversion in the jSLE group on D14 (p = 0.009), D28 (p = 0.023), D12m (p = 0.015) and D24m (p = 0.004). Cellular immune response to Bordetella pertussis showed significantly lower levels of IFNγ (p < 0.001) and higher levels of IL10, IL12, IL21 and TNFα in jSLE patients than controls. CONCLUSIONS: jSLE patients had good response to Tdap booster dose for the tetanus antigen, but not for diphtheria and pertussis. This vaccine was safe in relation to adverse events and absence of disease reactivation.

Tdap booster to adolescents with juvenile idiopathic arthritis on and off anti-TNF agents is safe and immunogenic.

INTRODUCTION: The response to vaccines in juvenile idiopathic arthritis (JIA) patients on and off anti-tumor necrosis factor (anti-TNF) agents remains highly discussed. There are no published studies on the immune response following a Tdap booster dose in JIA patients so far. OBJECTIVE: To evaluate the immune response and safety after a Tdap booster in JIA patients and in healthy adolescents. METHODS: Nineteen adolescents with JIA according to the ILAR criteria on anti-TNF medication, 19 adolescents with JIA off anti-TNF medication, and 27 healthy adolescents (control group) were compared after a Tdap booster. Adverse events and disease activity were evaluated. Lymphocyte immunophenotyping was performed by flow cytometry. Tetanus, diphtheria and pertussis toxin antibodies were assessed by ELISA; whole blood was stimulated with whole-cell pertussis, and supernatants were assessed for cytokines by xMAP. RESULTS: The three groups showed a similar frequency of adverse events. There was no disease reactivation after the Tdap booster. Tetanus, diphtheria and pertussis antibodies showed a significant response when D0 and D14 concentrations were compared in both JIA groups and controls. Over time, a different pattern of response to the Tdap booster was observed among the groups for tetanus antibodies (p = 0.005) but not for diphtheria and pertussis antibodies. In contrast to the protection attained for tetanus and diphtheria, in the three groups, not all individuals showed pertussis seroconversion at either D14 or D28. In addition, the seroconversion of three subjects with JIA on anti-TNF medication was not maintained at D28. JIA patients off anti-TNF showed a higher percentage of naive CD8 + T cells (p = 0.007) and central memory CD8 + cells (p = 0.003) and a lower percentage of effector CD8 + T cells (p = 0.003) and NK cell numbers (p = 0.018) than the control group. The JIA group off anti-TNF medication had fewer B lymphocytes than both the JIA group on anti-TNF medication and the control group (p = 0.016). Cellular immunity to Bordetella pertussis showed that IFNγ levels were significantly lower in both JIA groups than in the control group (p = 0.003), IL10 levels were higher in the JIA off anti-TNF group (p = 0.009), IL17A and IL5 levels were lower in the JIA on anti-TNF group than in the control group (p = 0.018 and p = 0.016, respectively); however, an increase in IFNγ (p = 0.008), IL17A (p = 0.030) and TNFα (p = 0.041) levels was observed at D14 in both patient groups. Both JIA groups showed higher levels of IL21 than the control group (p = 0.023). CONCLUSION: We conclude that individuals with JIA on or off anti-TNF agents showed a good response to a booster dose for the three antigens studied in the absence of major adverse events and without the reactivation of the disease.

Prevalence of Pathologic Findings in Panoramic Radiographs: Calcified Carotid Artery Atheroma.

OBJECTIVES: To assess the prevalence of images suggestive of calcified carotid artery atheromas (ISCCAA) in panoramic radiographs of patients under dental treatment. MATERIALS AND METHODS: The sample consisted of 8.338 panoramic radiographs from female (n=5.049) and male (n=3.289) patients under dental treatment between 4 and 94 years of age. The panoramic radiographs were evaluated searching for ISCCAA. The obtained findings were statistically associated with sex and age. RESULTS: ISCCAA were found in 579 radiographs (6.9%). No statistically significant differences were observed between females and males (p>0.05). ISCCAA were more prevalent in patients having a mean age of 50 (p<0.05). CONCLUSION: The potential cases of ISCCAA that were assessed on panoramic radiographs are of utmost clinical significance because they can ensure early and correct diagnosis.

Grupo de atividades de vida diária: influência do procedimento em pacientes adultos com acidente vascular encefálico isquêmico / Daily life activities group: the influence of the procedure in ischemic stroke adult patients

O acidente vascular encefálico (AVE) pode gerar seqüelas motorasacarretando dificuldades em vários aspectos funcionais da vida diáriado indivíduo. O terapeuta ocupacional pode intervir com essa população,com o objetivo de diminuir as limitações adquiridas. Uma das modalidades de tratamento é o atendimento em grupo, em função da riqueza das trocas existentes no mesmo. Este estudo visou analisar os resultados do procedimento do grupo de Atividades de Vida Diária(AVDs) composto por pacientes com seqüelas de AVE isquêmico. Foramincluídos 10 sujeitos com seqüelas de AVE isquêmico, que participaramdo grupo de AVDs, sendo os mesmos avaliados por meio da HAQ (Health Assessment Questionnaire) e da FAQ (Functional Activities Questionnaire), em dois momentos pré e pós intervenção. Para a análise dos dados foi utilizado o teste Wilcoxon com p ≤ 0,05. Após análise de resultados pré e pós intervenção verificou-se diferença significativa para ambos os instrumentos de avaliação (HAQ p=0.001 e FAQ p=0,0117). O estudo mostrou a eficácia do procedimento - grupo de AVDs, composto por sujeitos com sequelas de AVE isquêmico emfase crônica, através da mensuração dos ganhos funcionais obtidospela HAQ e FAQ. Estudos com um número maior de pacientes são necessários para uma maior generalização das conclusões.

Strokes affect people’s daily lives because they create difficulties in manyfunctional aspects of the individual’s daily life. Occupational therapistscan intervene with stroke patients by trying to decrease their acquiredlimitations. Treatment can be done individually or in groups whereexperiential interchange is possible. This study sought to analyze theprogress in the various Daily Life Activities (DLAs) of ischemic strokepatients. Ten patients were included in the study and were evaluated before and after the intervention using two different scales: the HAQ (Health Assessment Questionnaire) and the FAQ (Functional Activities Questionnaire). The Wilcoxon statistic test was used to analyze data with p ≤ 0.05. Analysis of results revealed statistical differences for both scales between the two analyzed moments (HAQ p=0.001 and FAQ p=0.0117). The study showed the effectiveness of the procedure on the progress of the DLAs for a group of subjects suffering from chronic ischemic EVA by measuring the functional gains shown in the HAQ and FAQ, but largerstudies are necessary to allow more generalized conclusions.