Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.

Background: Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement. Methods: Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels. Results: Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls. Conclusion: This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.

Invasive Meningococcal X Disease during the COVID-19 Pandemic, Brazil.

Invasive meningococcal disease persists as a fulminant disorder worldwide. Although cases caused by Neisseria meningitidis serogroup X (MenX) occur infrequently, outbreaks have been reported in countries in Africa in recent decades. We report 2 cases of MenX invasive meningococcal disease in São Paulo, Brazil, in 2021 and 2022, during the COVID-19 pandemic.

SARS-CoV-2 reinfection: report of two cases in Southeast Brazil.

From February 26, 2020 to March 11, 2021, coronavirus disease 2019 (COVID-19) pandemic resulted in 11,439,558 cases and 277,102 deaths in Brazil. Among them, 2,195,130 cases and 63,965 deaths occurred in Sao Paulo State, Southeast Brazil. The recent emergence and rise of new variants of SARS-CoV-2 is of concern because of their higher transmissibility and possible association with more severe disease. Cases of SARS-CoV-2 reinfections have been described since December 2020 in Brazil. This report describes two cases of COVID-19 reinfection, that occurred five and six months after the first infection, during the second wave of the pandemic in Sao Paulo State. Both patients presented mild symptoms in the two COVID-19 episodes and different lineages of SARS-CoV-2 were identified: B.1.1.33 and B.1.1.28 lineages in case 1 and B1.1.128 and P. 2 lineages in case 2.

SARS-CoV-2 reinfection: report of two cases in Southeast Brazil

From February 26, 2020 to March 11, 2021, coronavirus disease 2019 (COVID-19) pandemic resulted in 11,439,558 cases and 277,102 deaths in Brazil. Among them, 2,195,130 cases and 63,965 deaths occurred in Sao Paulo State, Southeast Brazil. The recent emergence and rise of new variants of SARS-CoV-2 is of concern because of their higher transmissibility and possible association with more severe disease. Cases of SARS-CoV-2 reinfections have been described since December 2020 in Brazil. This report describes two cases of COVID-19 reinfection, that occurred five and six months after the first infection, during the second wave of the pandemic in Sao Paulo State. Both patients presented mild symptoms in the two COVID-19 episodes and different lineages of SARS-CoV-2 were identified: B.1.1.33 and B.1.1.28 lineages in case 1 and B1.1.128 and P. 2 lineages in case 2.

Latent and Overt Polyautoimmunity in Children and Adolescents With Immune Thrombocytopenia.

Autoantibodies are biomarkers for autoimmune disease diagnosis, monitoring, and prediction. Therefore, this study established the frequency of latent and overt polyautoimmunity in children and adolescents with >6 months of diagnosis of immune thrombocytopenia (ITP). Forty-seven patients with chronic or persistent disease had non-organ-specific and organ-specific autoantibodies assessed. Frequency of latent polyautoimmunity was 36.2%, and, of overt polyautoimmunity, it was 4.3%. Of ITP patients with latent polyautoimmunity, 52.9% were positive for antinuclear antibody (ANA), 47.1% for autoantibodies other than ANA, and 64.7% for multiple autoantibodies. In addition, patients with latent polyautoimmunity and those positive for ANA were significantly older at disease onset. Both ITP patients positive and negative for autoantibodies reported family members with autoimmune diseases. The autoantibodies observed were as follows: ANA, anti-dsDNA, anti-SSA/Ro, IgM aCL, anti-GAD, anti-IA2, anti-IAA, anti-TG, anti-TPO, anti-LKM1, and SMA. Of ITP patients with overt polyautoimmunity, 1 was diagnosed with type 1 diabetes mellitus and the other with thyroiditis. In conclusion, children and adolescents with ITP present high frequency of latent and overt polyautoimmunity even for autoantibodies other than ANA. Therefore, ANA and other non-organ-specific and organ-specific autoantibodies should be considered for assessment during ITP patients' follow-up.

Increased sMer, but not sAxl, sTyro3, and Gas6 relate with active disease in juvenile systemic lupus erythematosus.

INTRODUCTION/OBJECTIVES: Tyro3, Axl, and Mer (TAM) receptors and ligands mediate apoptotic bodies engulfment which alteration has been related with juvenile systemic lupus erythematosus (JSLE) pathogenesis. Thus, the aim was to determine their soluble levels. METHODS: Serum sTyro3, sAxl, sMer, and Gas6 levels were measured using ELISA in 67 JSLE patients, 12 juvenile idiopathic arthritis (JIA) inflammatory and 20 healthy controls and related with SLEDAI-2K score, anti-dsDNA antibody, ESR, CRP, C3, C4 levels, and nephritis. RESULTS: JSLE patients with active disease (SLEDAI-2K> 4) had significantly increased sMer levels compared with healthy controls (median 8.4 vs. 6.0 ng/mL, p = 0.009) and inactive disease patients (5.2 ng/mL, p = 0.0003). sMer levels correlated with SLEDAI-2K (r = 0.44; p = 0.0004) and ESR (r = 0.24; p = 0.04), while sAxl correlated with SLEDAI-2K (r = 0.33; p = 0.008) and C4 levels (r = - 0.24; p = 0.04). JSLE patients taking glucocorticoid had increased sAxl and sMer levels. Moreover, sAxl correlated with sMer and sTyro3 levels. Patients with nephritis and those with focal or diffuse proliferative glomerulonephritis had these protein levels similar to healthy controls and patients without renal involvement. sTyro3 levels of JSLE patients taking glucocorticoid were decreased, and correlated with Gas6 and sAxl, while Gas6 levels correlated with age upon enrollment. JIA controls had protein levels similar to healthy controls and JSLE patients. CONCLUSIONS: This study reinforces that sMer is increased in active JSLE patients, yet sMer and sAxl correlates with disease activity parameters, and their alterations are disease-specific. However, further studies are needed to determine exact roles of sTyro3 and Gas6 in disease pathogenesis. Key Points • sMer and sAxl serum levels are related with active disease in JSLE patients • sMer correlated with SLEDAI-2K score in JSLE • sTyro3, sAxl, sMer and Gas6 levels did not related with nephritis in JSLE patients • sTyro3 and Gas6 exact roles in JSLE are not established and further studies are needed.

Increased Soluble Cytoplasmic Bcl-2 Protein Serum Levels and Expression and Decreased Fas Expression in Lymphocytes and Monocytes in Juvenile Dermatomyositis.

OBJECTIVE: To evaluate soluble Fas antigen (sFas), sFas ligand (sFasL), soluble tumor necrosis factor-related apoptosis-inducing ligand, and soluble cytoplasmic Bcl-2 protein (sBcl-2) serum levels, Fas and Bcl-2 expressions in T and B lymphocytes and monocytes and relations with erythrocyte sedimentation rate, C-reactive protein (CRP), Childhood Myositis Assessment Scale, and manual muscle testing in juvenile dermatomyositis (JDM). METHODS: Serum levels were determined by ELISA and peripheral cell expressions by flow cytometry for patients with JDM or juvenile idiopathic arthritis (JIA), and healthy controls. RESULTS: Patients with JDM had increased sBcl-2, which correlated with CRP. Expression of Bcl-2 was increased and expression of Fas was decreased in CD3+, CD4+, and CD8+ T lymphocytes compared with JIA and/or healthy controls. CONCLUSION: Patients with JDM presented a unique apoptosis-related proteins profile, which may contribute to disease development.

Increased serum sFas, sTRAIL, and reduced sFasL in juvenile-onset systemic lupus erythematosus.

The aims of this study were to assess serum Fas, FasL, TRAIL, and Bcl-2 levels in patients with juvenile-onset systemic lupus erythematosus (JSLE) and to evaluate their relations with disease activity parameters and nephritis. Forty-eight JSLE patients, 33 juvenile idiopathic arthritis (JIA, inflammatory controls) patients and 40 healthy controls were enrolled. sFas, sFasL, sTRAIL, and sBcl-2 serum levels were measured by ELISA. Disease activity parameters included SLEDAI score, ESR, anti-dsDNA antibodies, C3, and C4 levels. Thirty-five JSLE patients had nephritis and 32 patients were classified as having active disease (SLEDAI ≥4). Statistical analysis methods included Mann-Whitney test and Spearman's rank test. JSLE patients had significantly increased sFas serum levels compared with healthy controls (median 177.6 vs. 117.5 pg/mL; p = 0.0001), higher sTRAIL (median 484.6 vs 270.8 pg/mL; p = 0.02), and reduced sFasL (median 0.05 vs 0.3 ng/mL; p = 0.0002). The same results were observed for JSLE patients with active disease and for patients with nephritis. Additionally, sFas levels in JSLE patients directly correlated with SLEDAI score (r = 0.40; p = 0.009), and sTRAIL levels were increased in JSLE patients with neuropsychiatric disease compared with those without this involvement (median 667.9 vs. 216.2 pg/mL; p = 0.03). Otherwise, sBcl-2 levels of JSLE patients were similar to healthy controls. JIA patients had sFas, sFasL, sTRAIL, and sBcl-2 serum levels similar to JSLE patients and to healthy controls. In summary, this study characterized in JSLE a distinct profile from adult SLE that comprises increased sFas, sTRAIL, and reduced sFasL, notably in patients with active disease and with nephritis.

Low C4, C4A and C4B gene copy numbers are stronger risk factors for juvenile-onset than for adult-onset systemic lupus erythematosus.

OBJECTIVE: Complete deficiency of Complement C4 component is a strong genetic risk factor for SLE. C4 is encoded by two different genes, C4A and C4B, which show considerable gene copy number (GCN) variation. This study investigates the association of total C4, C4A and C4B GCN with JSLE. METHODS: Ninety JSLE patients, 170 adult-onset SLE (aSLE) patients and 200 healthy individuals were evaluated for C4A and C4B GCN by quantitative real-time PCR. RESULTS: JSLE patients had lower GCN for C4A (mean = 1.7; 95% CI: 1.5, 1.9) and C4B (mean = 1.5; 95% CI: 1.3, 1.6) compared with healthy individuals (mean C4A = 2.3; 95% CI: 2.2, 2.5, P < 0.001; C4B = 2.0; 95% CI: 1.8, 2.1; P < 0.001) or with aSLE patients (mean C4A = 1.9; 95% CI: 1.8, 2.1, P = 0.006; mean C4B = 1.8; 95% CI: 1.7, 1.9, P < 0.001). Low total C4 GCN (<4 copies) was more frequent in JSLE than in healthy individuals (59% vs 28%; P < 0.001). The same was observed for low C4A (⩽1 copy) (52% vs 18%; P < 0.001) and for low C4B (60% vs 31%; P < 0.001). JSLE had a stronger association with low total C4 (OR = 3.68, 95% CI: 2.19, 6.20), C4A (OR = 4.98, 95% CI: 2.88, 8.62) and C4B (OR = 3.26; 95% CI: 1.95, 5.47) than aSLE (C4 OR = 2.03; 95% CI: 1.32, 3.13; C4A OR = 2.36; 95% CI: 1.46, 3.81; C4B OR = 1.13; 95% CI: 0.73, 1.74). In addition, pericarditis in JSLE patients was associated with low C4 (OR = 4.13; 95% CI: 1.02, 16.68; P = 0.047) and low C4A (OR = 5.54; 95% CI: 1.37, 22.32; P = 0.016). CONCLUSION: Low total C4, C4A and C4B GCN were associated with a stronger risk for developing JSLE than aSLE. Additionally, low total C4 and C4A GCN are risk factors for pericarditis in JSLE.

Inflammasome polymorphisms in juvenile systemic lupus erythematosus.

Inflammasome is the cytoplasmic complex responsible for pro-IL1 ß cleavage and secretion of IL-1ß. Recently our group reported the first association between polymorphisms in the inflammasome receptor NLRP1 and adult-onset systemic lupus erythematosus (SLE) "di per se" and especially in SLE-associated renal disease, suggesting the involvement of NLRP1-inflammasome in the immune dysregulation characteristic of SLE patients. Considering that juvenile-onset SLE (JSLE) is more severe than adult SLE, and that the genetic background plays a major role in the early development of autoimmune diseases, we analysed selected polymorphisms in inflammasome genes (NLRP1, NLRP3, CARD8, IL1B, TNFAIP3) of children and adolescents with JSLE (n = 90) and in healthy controls (n = 144). A single polymorphism in IL1B, and not NLRP1, gene resulted in association with JSLE, suggesting that IL-1 ß is involved in the pathogenesis of SLE, but different genes could play specific role in adult- or early-onset disease.

Molecular characterization of the complement C1q, C2 and C4 genes in Brazilian patients with juvenile systemic lupus erythematosus.

OBJECTIVE: To perform a molecular characterization of the C1q, C2 and C4 genes in patients with juvenile systemic lupus erythematosus. METHODS: Patient 1 (P1) had undetectable C1q, patient 2 (P2) and patient 3 (P3) had decreased C2 and patient 4 (P4) had decreased C4 levels. All exons and non-coding regions of the C1q and C2 genes were sequenced. Mononuclear cells were cultured and stimulated with interferon gamma to evaluate C1q, C2 and C4 mRNA expression by quantitative real-time polymerase chain reaction. RESULTS: C1q sequencing revealed heterozygous silent mutations in the A (c.276 A>G Gly) and C (c.126 C>T Pro) chains, as well as a homozygous single-base change in the 3' non-coding region of the B chain (c*78 A>G). C1qA mRNA expression without interferon was decreased compared with that of healthy controls (p<0.05) and was decreased after stimulation compared with that of non-treated cells. C1qB mRNA expression was decreased compared with that of controls and did not change with stimulation. C1qC mRNA expression was increased compared with that of controls and was even higher after stimulation. P2 and P3 had Type I C2 deficiency (heterozygous 28 bp deletion at exon 6). The C2 mRNA expression in P3 was 23 times lower compared with that of controls and did not change after stimulation. The C4B mRNA expression of P4 was decreased compared with that of controls and increased after stimulation. CONCLUSIONS: Silent mutations and single-base changes in the 3' non-coding regions may modify mRNA transcription and C1q production. Type I C2 deficiency should be evaluated in JSLE patients with decreased C2 serum levels. Further studies are needed to clarify the role of decreased C4B mRNA expression in JSLE pathogenesis.

Outbreak of Neisseria meningitidis C in a Brazilian oil refinery involving an adjacent community.

BACKGROUND: An outbreak of serogroup C meningococcal disease (MD) that involved employees from an oil refinery occurred in Paulínia, from March to June 2010, and spread to the community of Cosmópolis, both situated in São Paulo State, Brazil. The aim of this study was to describe the epidemiological and laboratory aspects, and the control measures that were implemented. METHODS: Descriptive and molecular epidemiological analysis was used to define the extent of the outbreak and the common risk factors among outbreak related cases. Vaccination initiative targeted the employees from the oil refinery and the community-based individuals. RESULTS: A total of six outbreak-related cases of MD in the oil refinery and 12 cases in the city of Cosmópolis, São Paulo State occurred in a three-month period. All 18 MD cases were confirmed as serogroup C either by culture, real time polymerase chain reaction (RT-PCR), or counterimmunoelectrophoresis (CIE). The meningococcal isolates (n=15) had the phenotype C:23:P1.14-6 and showed close genetic relationship by pulsed field gel electrophoresis (PFGE). Multilocus sequence typing (MLST) characterization showed that the clones were ST 3780, ST-103 complex. The isolates were susceptible to the antibiotics tested. Vaccination was administered to 15,848 persons at the oil refinery and 18,571 persons of the community. CONCLUSIONS: The molecular characterization of the Neisseria meningitidis (N. meningitidis) strains, and the efficient investigation and the prompt measures implemented were essential for controlling the disease in the region.

Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. METHODS: The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. RESULTS: Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 ± 163.4 IU/ml (range 3.5-9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 ± 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels (r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). CONCLUSIONS: The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus

OBJECTIVE: The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. METHODS: The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. RESULTS: Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 ± 163.4 IU/ml (range 3.5-9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 ± 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels (r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). CONCLUSIONS: The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

Vaccination practice in children with rheumatic disease.

INTRODUCTION/OBJECTIVES: Evaluate clinical practice through assessment of vaccination card and recommendation of specific vaccines in pediatric patients with rheumatic diseases in use of different drugs and reveal the possible association between vaccination frequency and time of the clinical practice of pediatric rheumatologists in the state of São Paulo. MATERIAL AND METHODS: A questionnaire was sent to pediatric rheumatologists of the Departamento de Reumatologia da Sociedade de Pediatria de São Paulo. This instrument included questions about practice time on Pediatric Rheumatology, vaccination of patients with juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and immunization according to the treatments used. RESULTS: Vaccination card was seen by 100% of the professionals at the first visit and by 36% annually. Vaccines of live agents were not recommended for patients with JSLE, JIA, and JDM in 44%, 64%, and 48%, respectively. The professionals were divided into two groups: Group A (≤ 15 years of practice, n = 12) and B (≥ 16 years, n = 13). No statistical difference was observed in the use of live agent vaccine and vaccines with inactivated agents or protein components in the two treatment groups (P > 0.05). Moreover, the groups had similar opinion regarding severity of immunosuppression in patients with JSLE, JIA, and JDM (with or without activity) and treatment used (P > 0.05). CONCLUSIONS: The frequency of immunization by pediatric rheumatologists in São Paulo is low, especially after the first visit, and not influenced by time of professional practice.

Prática de vacinação em crianças com doenças reumáticas / Vaccination practice in children with rheumatic disease

INTRODUÇÃO/OBJETIVOS: Avaliar a prática clínica com relação à verificação do cartão vacinal e à indicação de vacinas específicas em pacientes com doenças reumáticas pediátricas em uso de diferentes drogas, e evidenciar a possível associação entre frequência de vacinação e tempo de prática clínica dos reumatologistas pediátricos do estado de São Paulo. MATERIAL E MÉTODOS: Um questionário foi enviado para os reumatologistas pediátricos do Departamento de Reumatologia da Sociedade de Pediatra de São Paulo. Esse instrumento incluiu questões sobre tempo de prática em Reumatologia Pediátrica, vacinação de pacientes com Lúpus Eritematoso Sistêmico Juvenil (LESJ), artrite idiopática juvenil (AIJ), dermatomiosite juvenil (DMJ) e imunização de acordo com os tratamentos utilizados. RESULTADOS: Cartão de vacinação foi visto por 100 por cento dos profissionais na primeira consulta e por 36 por cento anualmente. Vacinas de agentes vivos não foram recomendadas para pacientes com LESJ, AIJ e DMJ em 44 por cento, 64 por cento e 48 por cento, respectivamente. Os profissionais foram divididos em dois grupos: A (< 15 anos de prática, n = 12) e B (> 16 anos, n = 13). Nenhuma diferença estatística foi observada no uso de vacinas de agentes vivos e vacinas de agentes inativos ou componentes proteicos em relação ao tratamento nos dois grupos (P > 0,05). Além disso, os grupos foram similares em relação à opinião sobre a gravidade de imunossupressão em pacientes com LESJ, AIJ e DMJ com ou sem atividade e a terapêutica utilizada (P > 0,05). CONCLUSÕES: A frequência de vacinação por reumatologistas pediátricos de São Paulo é baixa, especialmente após a primeira consulta, e não é influenciada pelo tempo de prática profissional.

INTRODUCTION/OBJECTIVES: Evaluate clinical practice through assessment of vaccination card and recommendation of specific vaccines in pediatric patients with rheumatic diseases in use of different drugs and reveal the possible association between vaccination frequency and time of the clinical practice of pediatric rheumatologists in the state of São Paulo. MATERIAL AND METHODS: A questionnaire was sent to pediatric rheumatologists of the Departamento de Reumatologia da Sociedade de Pediatria de São Paulo. This instrument included questions about practice time on Pediatric Rheumatology, vaccination of patients with juvenile systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM), and immunization according to the treatments used. RESULTS: Vaccination card was seen by 100 percent of the professionals at the first visit and by 36 percent annually. Vaccines of live agents were not recommended for patients with JSLE, JIA, and JDM in 44 percent, 64 percent, and 48 percent, respectively. The professionals were divided into two groups: Group A (< 15 years of practice, n = 12) and B (> 16 years, n = 13). No statistical difference was observed in the use of live agent vaccine and vaccines with inactivated agents or protein components in the two treatment groups (P > 0.05). Moreover, the groups had similar opinion regarding severity of immunosuppression in patients with JSLE, JIA, and JDM (with or without activity) and treatment used (P > 0.05). CONCLUSIONS: The frequency of immunization by pediatric rheumatologists in São Paulo is low, especially after the first visit, and not influenced by time of professional practice.

The role of apoptosis proteins and complement components in the etiopathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus is a prototypical autoimmune disease characterized by the deregulation of T and B cells, tissue infiltration by mononuclear cells, tissue damage and the production of autoantibodies. There is a consensus that accelerated apoptosis of circulating lymphocytes and/or impaired clearance of apoptotic bodies may increase the amount of nuclear antigens presented to T lymphocytes. This process is accompanied by autoimmune responses that can lead to the development of lupus. The dysfunction of apoptosis may be a direct consequence of alterations in proteins/genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto-reactive cells, and the lack of C1q could impair the clearance of self-antigens. The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression. This review summarizes the role of each component of the apoptotic process in the pathogenesis of lupus.

The role of apoptosis proteins and complement components in the etiopathogenesis of systemic lupus erythematosus

Systemic lupus erythematosus is a prototypical autoimmune disease characterized by the deregulation of T and B cells, tissue infiltration by mononuclear cells, tissue damage and the production of autoantibodies. There is a consensus that accelerated apoptosis of circulating lymphocytes and/or impaired clearance of apoptotic bodies may increase the amount of nuclear antigens presented to T lymphocytes. This process is accompanied by autoimmune responses that can lead to the development of lupus. The dysfunction of apoptosis may be a direct consequence of alterations in proteins/genes such as Fas, Bcl-2 and C1q. Increased expression of Fas antigen could intensify the exposure of hidden antigens. The overexpression of Bcl-2 protein might inhibit the removal of auto-reactive cells, and the lack of C1q could impair the clearance of self-antigens. The complete knowledge of the role of apoptosis components in the etiopathogenesis of lupus could lead to the development of new therapies targeting the apoptotic threshold, which could result in a more specific and effective disease response compared to global immunosuppression. This review summarizes the role of each component of the apoptotic process in the pathogenesis of lupus.