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1.
Artigo em Inglês | MEDLINE | ID: mdl-31174697

RESUMO

TLRs, Siglecs and CD163 are cell surface receptors that play an important role in immune response and sepsis. The objective of this study was to assess changes in the expression levels of several of these receptors (TLR2, TLR4, CD163, Siglec-1, Siglec-3, Siglec-5 and Siglec-10) on the surface of peripheral blood mononuclear cells from pigs with sepsis caused by Haemophilus parasuis. Flow cytometry was employed to analyze samples from an experimental infection and from cell cultures. A significant increase in CD163, TLR2 and Siglec-3 expression during infection was seen. However, in vitro exposure of peripheral blood monocytes to bacteria or sera from infected pigs did not increase the expression of these receptors. These changes may be due to recruitment of monocytes into the blood compartment in response to H. parasuis-induced sepsis.

2.
J Allergy Clin Immunol Pract ; 7(6): 1793-1802.e2, 2019 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30772477

RESUMO

BACKGROUND: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT). OBJECTIVE: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC). METHODS: Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Patients with frequent angioedema attacks, either study treatment-naive or who had completed COMPACT, were randomly assigned (1:1) to 40 IU/kg or 60 IU/kg C1-INH(SC) twice per week, with conditional uptitration to optimize prophylaxis (ClinicalTrials.gov registration no. NCT02316353). RESULTS: A total of 126 patients with a monthly attack rate of 4.3 in 3 months before entry in COMPACT were enrolled and treated for a mean of 1.5 years; 44 patients (34.9%) had more than 2 years of exposure. Mean steady-state C1-INH functional activity increased to 66.6% with 60 IU/kg. Incidence of adverse events was low and similar in both dose groups (11.3 and 8.5 events per patient-year for 40 IU/kg and 60 IU/kg, respectively). For 40 IU/kg and 60 IU/kg, median annualized attack rates were 1.3 and 1.0, respectively, and median rescue medication use was 0.2 and 0.0 times per year, respectively. Of 23 patients receiving 60 IU/kg for more than 2 years, 19 (83%) were attack-free during months 25 to 30 of treatment. CONCLUSIONS: In patients with frequent HAE attacks, long-term replacement therapy with C1-INH(SC) is safe and exhibits a substantial and sustained prophylactic effect, with the vast majority of patients becoming free from debilitating disease symptoms.

4.
Clin Transl Allergy ; 8: 42, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30338053

RESUMO

The objective of this analysis was to evaluate the change over time in age at first symptoms, age at diagnosis, and delay in diagnosis using data from the Icatibant Outcome Survey (IOS). Patients with a diagnosis of C1-INH-HAE who were born before the year 1990 and who were diagnosed before they reached 25 years of age were included in the analysis. Both age at diagnosis and delay in diagnosis of C1-INH-HAE appear to decline with later decade of birth, despite wide variation across the countries assessed, suggesting that improved disease awareness causes increased rates of earlier diagnosis over time. Our findings demonstrate that some patients are still experiencing long delays to diagnosis, indicating an ongoing need for improved disease awareness.

6.
Front Immunol ; 9: 1584, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065721

RESUMO

Allergic diseases, such as respiratory, cutaneous, and food allergy, have dramatically increased in prevalence over the last few decades. Recent research points to a central role of the microbiome, which is highly influenced by multiple environmental and dietary factors. It is well established that the microbiome can modulate the immune response, from cellular development to organ and tissue formation exerting its effects through multiple interactions with both the innate and acquired branches of the immune system. It has been described at some extent changes in environment and nutrition produce dysbiosis in the gut but also in the skin, and lung microbiome, inducing qualitative and quantitative changes in composition and metabolic activity. Here, we review the potential role of the skin, respiratory, and gastrointestinal tract (GIT) microbiomes in allergic diseases. In the GIT, the microbiome has been proven to be important in developing either effector or tolerant responses to different antigens by balancing the activities of Th1 and Th2 cells. In the lung, the microbiome may play a role in driving asthma endotype polarization, by adjusting the balance between Th2 and Th17 patterns. Bacterial dysbiosis is associated with chronic inflammatory disorders of the skin, such as atopic dermatitis and psoriasis. Thus, the microbiome can be considered a therapeutical target for treating inflammatory diseases, such as allergy. Despite some limitations, interventions with probiotics, prebiotics, and/or synbiotics seem promising for the development of a preventive therapy by restoring altered microbiome functionality, or as an adjuvant in specific immunotherapy.

7.
Vet Microbiol ; 219: 123-127, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29778184

RESUMO

PRRSV can replicate for months in lymphoid organs leading to persistent host infections. Porcine bone marrow comprises two major monocyte subsets, one of which expresses CD163 and CD169, two receptors involved in the entry of PRRSV in macrophages. In this study, we investigate the permissiveness of these subsets to PRRSV infection. PRRSV replicates efficiently in BM CD163+ monocytes reaching titers similar to those obtained in alveolar macrophages, but with a delayed kinetics. Infection of BM CD163- monocytes was variable and yielded lower titers. This may be related with the capacity of BM CD163- monocytes to differentiate into CD163+ CD169+ cells after culture in presence of M-CSF. Both subsets secreted IL-8 in response to virus but CD163+ cells tended to produce higher amounts. The infection of BM monocytes by PRRSV may contribute to persistence of the virus in this compartment and to hematological disorders found in infected animals such as the reduction in the number of peripheral blood monocytes.


Assuntos
Células da Medula Óssea/virologia , Medula Óssea/imunologia , Monócitos/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/fisiologia , Animais , Antígenos CD/efeitos dos fármacos , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/efeitos dos fármacos , Antígenos de Diferenciação Mielomonocítica/imunologia , Medula Óssea/virologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Células Cultivadas , Interações Hospedeiro-Patógeno/imunologia , Interleucina-8/imunologia , Interleucina-8/metabolismo , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/farmacologia , Monócitos/classificação , Monócitos/imunologia , Síndrome Respiratória e Reprodutiva Suína/virologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Superfície Celular/imunologia , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/efeitos dos fármacos , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Suínos , Replicação Viral
8.
Orphanet J Rare Dis ; 13(1): 51, 2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29631595

RESUMO

BACKGROUND: Hereditary angioedema with C1 inhibitor deficiency is a disabling, potentially fatal condition characterized by recurrent episodes of swelling. Self-treatment is recommended, in order to reduce admissions to the Emergency Room and the time between the onset of the attack and the treatment, resulting in a better treatment outcome and an improved quality of life (QoL). The purpose of this study is to assess the safety, tolerability, and effect on QoL of self-administration of pnf C1-INH for IV use (Berinert®). METHODS: An observational, monocenter, prospective study was designed. Patients referring to a center for angioedema that attended two sessions of self-infusion training course in the period March 2014-July 2015 were enrolled in the study. The primary endpoint was to monitor the safety and feasibility of pnf C1-INH self-infusion. The secondary endpoint was to evaluate the effect of self-infusion on the QoL, by means of the HAE-QoL questionnaire and the need for access to Emergency Room for infusion of Berinert®. Patients' medical history data were collected upon the first visit and questionnaires were filled after each attack treated with Berinert® (diary and Treatment Satisfaction Questionnaire for Medication) and upon the first visit and the follow-ups (HAE-QoL). RESULTS: Twenty patients were enrolled (median age = 42, IQR: 39-49; 60% females). Fifteen patients completed the study. A total of 189 attacks were recorded (annual median rate of 4 attacks/patient). Patients waited a median of 2 h (IQR: 1-4) before self-administration, and the resolution of the attack occurred after a median of 6 h (IQR: 4-11). Most attacks were abdominal (39%) and peripheral (22%). 92% of the attacks were treated through self-/caregiver-administration. In most attacks no side effects were reported. The number of attacks with side effects decreased over time, from 37% to 13%. Global satisfaction grew over time during the study period, reaching statistical significance over the first 6 months. The median total HAE-QoL score at baseline was 86 (IQR: 76-103) and improved in a non-significant manner throughout the study period. 8% of the attacks treated with Berinert® required ER admission/healthcare professional help in the study period, compared with 100% in the 3 years before enrollment (p < 0.0001). CONCLUSIONS: Self-administration of pnf C1-INH is safe, and increases patients' confidence in the treatment, showing also a trend towards an improvement in QoL. It reduces the need for ER admission/healthcare professionals help for the acute attacks, as well as the related costs.

9.
Clin Transl Allergy ; 8: 11, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29599966

RESUMO

Background: Icatibant is a bradykinin B2-receptor antagonist used for the treatment of hereditary angioedema attacks resulting from C1-inhibitor deficiency. Treatment is not adjusted by body weight however the impact of body mass index (BMI) on the effectiveness of icatibant is not documented in the literature. We examined disease characteristics and icatibant treatment effectiveness in patients stratified by BMI in the Icatibant Outcome Survey, an ongoing, international, observational study monitoring the real-world safety and effectiveness of icatibant. Methods: Attack and treatment characteristics as well as outcomes following treatment with icatibant were compared among patients with underweight, normal, overweight, and obese BMI. Results: Data from 2697 icatibant-treated attacks in 342 patients (3.5, 44.7, 34.8, and 17.0% patients of underweight, normal, overweight, and obese BMI, respectively) were analyzed. There was no significant difference in the frequency and severity of attacks across BMI groups, although obese patients tended to have more attacks of high severity. There was no impact of BMI on the frequency of laryngeal attacks, but patients with normal BMI had fewer cutaneous attacks and more abdominal attacks. Most attacks (71.9-83.8%) were treated with a single icatibant injection without the need for rescue with plasma-derived C1-inhibitor (pdC1-INH), regardless of BMI. Patients with obese BMI used pdC1-INH as rescue treatment more often (P < 0.0001; P = 0.0232 excluding 2 outliers) and treated attacks earlier than patients with normal BMI (P = 0.007). Furthermore, time to resolution and duration of attack were shorter for patients with high BMI (P < 0.001 for overweight and P < 0.05 for obese versus normal). Conclusion: Overall, icatibant was comparatively effective in treating attacks in patients across all BMI groups.Trial registration NCT01034969.

10.
J Allergy Clin Immunol Pract ; 6(5): 1733-1741.e3, 2018 Sep - Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29391286

RESUMO

BACKGROUND: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) impairs health-related quality of life (HRQoL). OBJECTIVE: The objective of this study was to assess HRQoL outcomes in patients self-administering subcutaneous C1-INH (C1-INH[SC]; HAEGARDA) for routine prevention of HAE attacks. METHODS: Post hoc analysis of data from the placebo-controlled, crossover phase III COMPACT study (Clinical Studies for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy). Ninety patients with C1-INH-HAE were randomized to 1 of 4 treatment sequences: C1-INH(SC) 40 or 60 IU/kg twice weekly for 16 weeks, preceded or followed by 16 weeks of twice weekly placebo injections. All HAE attacks were treated with open-label on-demand treatment as necessary. HRQoL assessments at week 14 (last visit) included the European Quality of Life-5 Dimensions Questionnaire (EQ-5D-3L), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication (TSQM). RESULTS: Compared with placebo (on-demand treatment alone), treatment with twice weekly C1-INH(SC) (both doses combined) was associated with better EQ-5D visual analog scale general health, less HADS anxiety, less WPAI presenteeism, work productivity loss, and activity impairment, and greater TSQM effectiveness and overall treatment satisfaction. More patients self-reported a "good/excellent" response during routine prevention with C1-INH(SC) compared with on-demand only (placebo prophylaxis) management. For each HRQoL measure, a greater proportion of patients had a clinically meaningful improvement during C1-INH(SC) treatment compared with placebo. CONCLUSIONS: In patients with frequent HAE attacks, a treatment strategy of routine prevention with self-administered twice weekly C1-INH(SC) had a greater impact on improving multiple HAE-related HRQoL impairments, most notably anxiety and work productivity, compared with on-demand treatment alone (placebo prophylaxis).

11.
Dev Comp Immunol ; 81: 95-104, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29175054

RESUMO

Monocytes comprise several subsets with distinct phenotypes and functional capacities. Based on CD163 expression, two major monocyte subsets can be discriminated in the porcine bone marrow. The CD163+ cells expressed higher levels of SLA-DR, Siglec-1, CD11R1 and CD16 when compared to CD163- monocytes, whereas no remarkable differences were observed in the expression of other markers analyzed. Gene expression analysis showed differential expression of several chemokine receptor and TLR genes. Both subsets phagocytosed microspheres with similar efficiency. However, CD163- cells tended to produce higher levels of ROS in response to PMA, whereas CD163+ cells were more efficient in endocytosing and processing antigens (DQ-OVA). CD163- monocytes produced higher levels of TNF-α and IL-10 than CD163+ cells when stimulated with LPS or Imiquimod. Both subsets produced similar amounts of IL-8 in response to LPS; however, CD163+ cells produced more IL-8 after Imiquimod stimulation. Whether these subsets represent different developmental stages, and how are they related remain to be investigated.


Assuntos
Células da Medula Óssea/imunologia , Monócitos/imunologia , Suínos/imunologia , Aminoquinolinas/imunologia , Animais , Apresentação do Antígeno , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Células Cultivadas , Endocitose , Antígenos de Histocompatibilidade/metabolismo , Imiquimode , Interleucina-10/metabolismo , Interleucina-8/metabolismo , Lipopolissacarídeos/imunologia , Estresse Oxidativo , Fenótipo , Receptores de Superfície Celular/metabolismo , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
Front Med (Lausanne) ; 4: 212, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29255709

RESUMO

Hereditary angioedema (HAE) is a group of rare, potentially life-threatening, and frequently debilitating diseases characterized by recurrent, and often with an unpredictable onset, of swelling attacks. HAE is heterogeneous, with considerable differences between its subtypes, patients, and even within the same patient over time. During the past few years, several new on demand and prophylactic therapies have become available for HAE, allowing for individualized treatment. Therefore, to optimize HAE management, it is important to determine in all patients, the severity of their attacks, their disease activity, its therapeutic control, and its impact on their quality of life. In this manuscript, we review the existing tools to assess these aspects of HAE management, many of which are patient-reported outcome instruments. Also, we outline the current gaps of knowledge and what tools are still missing to allow for a comprehensive assessment of all patients with HAE including children.

13.
Immunol Allergy Clin North Am ; 37(3): 597-616, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28687112

RESUMO

Burden of illness studies and evaluation of health-related quality of life using validated questionnaires have become an important task in the comprehensive management of angioedema conditions, mainly angioedema associated with chronic spontaneous urticaria and hereditary angioedema caused by C1-inhibitor deficiency. A review of the principal tools and studies is presented. Both diseases present a higher proportion of psychiatric disorders, impair work and studies productivity, and produce high direct and indirect costs. These assessments also have been useful to evaluate the positive impact of new drugs and interventions. More studies are desirable, especially in other types of angioedema disorders, such as hereditary angioedema with normal C1 inhibitor.


Assuntos
Angioedema/epidemiologia , Efeitos Psicossociais da Doença , Qualidade de Vida , Angioedema/tratamento farmacológico , Angioedema/psicologia , Ansiedade/etiologia , Depressão/etiologia , Gerenciamento Clínico , Humanos , Avaliação de Resultados da Assistência ao Paciente , Medidas de Resultados Relatados pelo Paciente , Inquéritos e Questionários
14.
Artigo em Inglês | MEDLINE | ID: mdl-28690642

RESUMO

BACKGROUND: Patients with hereditary angioedema (HAE) due to C1-inhibitor deficiency (C1-INH-HAE) experience recurrent attacks of cutaneous or submucosal edema that may be frequent and severe; prophylactic treatments can be prescribed to prevent attacks. However, despite the use of long-term prophylaxis (LTP), breakthrough attacks are known to occur. We used data from the Icatibant Outcome Survey (IOS) to evaluate the characteristics of breakthrough attacks and the effectiveness of icatibant as a treatment option. METHODS: Data on LTP use, attacks, and treatments were recorded. Attack characteristics, treatment characteristics, and outcomes (time to treatment, time to resolution, and duration of attack) were compared for attacks that occurred with versus without LTP. RESULTS: Data on 3228 icatibant-treated attacks from 448 patients with C1-INH-HAE were analyzed; 30.1% of attacks occurred while patients were using LTP. Attack rate, attack severity, and the distribution of attack sites were similar across all types of LTP used, and were comparable to the results found in patients who did not receive LTP. Attacks were successfully treated with icatibant; 82.5% of all breakthrough attacks were treated with a single icatibant injection without C1-INH rescue medication. Treatment outcomes were comparable for breakthrough attacks across all LTP types, and for attacks without LTP. CONCLUSIONS: Patients who use LTP should be aware that breakthrough attacks can occur, and such attacks can be severe. Thus, patients with C1-INH-HAE using LTP should have emergency treatment readily available. Data from IOS show that icatibant is effective for the treatment of breakthrough attacks. Trial Registration NCT01034969.

15.
J Allergy Clin Immunol Pract ; 5(6): 1671-1678.e2, 2017 Nov - Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28601641

RESUMO

BACKGROUND: Clinical manifestations of hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) usually begin in childhood, often intensifying during puberty. Currently there are insufficient efficacy/safety data for HAE therapies in children and adolescents due to the small number of pediatric patients enrolled in studies. OBJECTIVE: The objective of this phase 3 study was to evaluate the efficacy/safety of a single subcutaneous dose of icatibant (0.4 mg/kg; maximum 30 mg) in pediatric patients with C1-INH-HAE. METHODS: Patients aged 2 years to younger than 18 years were categorized as prepubertal (children) and pubertal/postpubertal (adolescents). The primary end point was time to onset of symptom relief-earliest time posttreatment to 20% or more improvement in composite symptom score. RESULTS: Thirty-two patients received icatibant (safety population: 11 children with attack, 10 adolescents without attack, and 11 adolescents with attack). The efficacy population consisted of 11 children and 11 adolescents with edematous attacks. Most attacks in the efficacy population (16 [72.7%]) were cutaneous, 5 (22.7%) were abdominal, and 1 (4.5%) was both cutaneous and abdominal; none was laryngeal. Overall, the median time to onset of symptom relief was 1.0 hour, the same for children and adolescents. Thirty-two treatment-emergent adverse events (all mild or moderate) occurred in 9 (28.1%) patients. Gastrointestinal symptoms were most common (9 events in 3 [9.4%] patients). Injection-site reactions affected most (90.6%) patients (particularly erythema and swelling), but almost all resolved by 6 hours postdose. Icatibant demonstrated a monophasic plasma concentration-time profile. Time to peak concentration was approximately 0.5 hours postdose. CONCLUSIONS: Symptom relief was rapid, and a single icatibant injection in pediatric patients with C1-INH-HAE was well tolerated (ClinicalTrials.gov identifier, NCT01386658).


Assuntos
Angioedemas Hereditários/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antagonistas de Receptor B2 da Bradicinina/uso terapêutico , Bradicinina/análogos & derivados , Proteína Inibidora do Complemento C1/genética , Adolescente , Asfixia , Bradicinina/uso terapêutico , Criança , Pré-Escolar , Proteína Inibidora do Complemento C1/metabolismo , Feminino , Humanos , Injeções Subcutâneas , Masculino , Puberdade , Resultado do Tratamento
16.
N Engl J Med ; 376(12): 1131-1140, 2017 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-28328347

RESUMO

BACKGROUND: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks. METHODS: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly followed by placebo, or vice versa. The primary efficacy end point was the number of attacks of angioedema. Secondary efficacy end points were the proportion of patients who had a response (≥50% reduction in the number of attacks with CSL830 as compared with placebo) and the number of times that rescue medication was used. RESULTS: Of the 90 patients who underwent randomization, 79 completed the trial. Both doses of CSL830, as compared with placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; P<0.001 for both comparisons). Response rates were 76% (95% CI, 62 to 87) in the 40-IU group and 90% (95% CI, 77 to 96) in the 60-IU group. The need for rescue medication was reduced from 5.55 uses per month in the placebo group to 1.13 uses per month in the 40-IU group and from 3.89 uses in the placebo group to 0.32 uses per month in the 60-IU group. Adverse events (most commonly mild and transient local site reactions) occurred in similar proportions of patients who received CSL830 and those who received placebo. CONCLUSIONS: In patients with hereditary angioedema, the prophylactic use of a subcutaneous C1 inhibitor twice weekly significantly reduced the frequency of acute attacks. (Funded by CSL Behring; COMPACT EudraCT number, 2013-000916-10 , and ClinicalTrials.gov number, NCT01912456 .).


Assuntos
Proteína Inibidora do Complemento C1/administração & dosagem , Angioedema Hereditário Tipos I e II/prevenção & controle , Adulto , Proteína Inibidora do Complemento C1/efeitos adversos , Proteína Inibidora do Complemento C1/metabolismo , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Angioedema Hereditário Tipos I e II/classificação , Humanos , Injeções Subcutâneas , Masculino , Risco , Autoadministração , Índice de Gravidade de Doença
18.
Artigo em Inglês | MEDLINE | ID: mdl-28115964

RESUMO

BACKGROUND: Hereditary angioedema (HAE) is a rare but serious condition characterized by recurrent spontaneous attacks of angioedema affecting superficial tissues of upper respiratory and gastrointestinal tracts. The potentially fatal and disfiguring nature of HAE impacts the health-related quality of life (HRQoL) of patients with this condition. OBJECTIVES: To assess the health-related quality of life of Canadian patients with HAE using the 36-item Short-Form Health Survey (SF-36v2). METHODS: Twenty-one patients living in Canada over age 18 with known diagnosis of hereditary angioedema due to C1-INH deficiency (HAE), completed the SF-36v2 (generic HRQoL questionnaire). Results were compared to Canadian normative data by converting the SF-36 scores into z scores. RESULTS: The SF-36v2 showed a significant reduction in general health (p = 0.0063) in patients with HAE when compared with healthy Canadians. Percentage of patients with z scores below 0.8 (large effect) was 47.6% for general health subscale, 33.3% for bodily pain and vitality subscales and 28.6% for physical component scores. Mean scores of eight dimensions ranged from 57.7 to 88.9. Mean Physical and mental component scores were 49.1 and 50.4. Internal consistency of evaluation was demonstrated by Cronbach's alpha value above 0.7 for all scales. General perception of health was significantly different in these patients, compared to Canadian normative data. CONCLUSIONS: This study of Canadian patients with HAE shows that General Health is most frequently affected followed by Bodily Pain and Vitality, as measured by SF-36v2. The SF-36v2 offers valuable insight to assess quality of life in patients with HAE, however a larger number of Canadian patients and specific tools for assessment are needed for better evaluation.

19.
Vet Microbiol ; 198: 72-80, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28062010

RESUMO

CD169 and CD163 have been involved in the process of PRRS virus attachment and infection in macrophages, although recent studies have challenged the requirement for CD169. In addition to CD169, macrophages express other siglecs, whose role in PRRS virus infection is so far unknown. Splenic CD163+ macrophages express Siglec-3 and Siglec-5 but almost undetectable levels of CD169. Hence, we considered this cell population appropriate for analysing the role of these siglecs in the attachment and internalization of PRRS virus into macrophages. PRRS virus replicated efficiently in these macrophages, yielding even higher titres than in alveolar macrophages. Besides, a recombinant protein consisting in the ectodomain of porcine Siglec-3 fused to the Fc fragment of human IgG1 (Siglec3-Fc) was able to bind PRRS virus, while binding to Siglec-5-Fc was inconsistent. Antibodies to CD169 but not to Siglec-3 or Siglec-5 blocked the binding and infection of PRRS virus on alveolar macrophages. Unexpectedly, our antibody to CD169 also blocked the binding of PRRS virus to splenic CD163+ macrophages, whereas antibodies to Siglec-3 or Siglec-5 had no effect. These results show that very low levels of CD169 expression are enough to support the attachment and internalization of PRRS virus into macrophages, whereas Siglec-3 and Siglec-5 do not seem to contribute to the virus entry in these cells.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Macrófagos/metabolismo , Macrófagos/virologia , Síndrome Respiratória e Reprodutiva Suína/fisiopatologia , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Receptores de Superfície Celular/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Animais , Anticorpos/metabolismo , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Síndrome Respiratória e Reprodutiva Suína/imunologia , Síndrome Respiratória e Reprodutiva Suína/metabolismo , Síndrome Respiratória e Reprodutiva Suína/virologia , Ligação Proteica , Domínios Proteicos/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , Suínos , Ligação Viral , Internalização do Vírus , Replicação Viral
20.
Cytometry B Clin Cytom ; 92(5): 361-370, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27598686

RESUMO

BACKGROUND: Although consensus guidelines have been proposed in 2010 for the diagnostic screening of paroxysmal nocturnal hemoglobinuria (PNH) by flow cytometry (FCM), so far no study has investigated the efficiency of such medical indications in multicentric vs. reference laboratory settings. METHODS: Here we evaluate the efficiency of consensus medical indications for PNH testing in 3,938 peripheral blood samples submitted to FCM testing in 24 laboratories in Spain and one reference center in Brazil. RESULTS: Overall, diagnostic screening based on consensus medical indications was highly efficient (14% of PNH+ samples) both in the multicenter setting in Spain (10%) and the reference laboratory in Brazil (16%). The highest frequency of PNH+ cases was observed among patients screened because of bone marrow (BM) failure syndrome (33%), particularly among those with aplastic anemia (AA; 45%) and to a less extent also a myelodysplastic syndrome (MDS; 10%). Among the other individuals studied, the most efficient medical indications for PNH screening included: hemolytic anemia (19%), hemoglobinuria (48%) and unexplained cytopenias (9%). In contrast, only a minor fraction of the patients who had been submitted for PNH testing because of unexplained thrombosis in the absence of cytopenia, were positive (0.4%). CONCLUSIONS: In summary, our results demonstrate that the current medical indications for PNH screening by FCM are highly efficient, although improved screening algorithms are needed for patients presenting with thrombosis and normal blood cell counts. © 2016 International Clinical Cytometry Society.


Assuntos
Anemia Aplástica/diagnóstico , Eritrócitos/citologia , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/epidemiologia , Síndromes Mielodisplásicas/diagnóstico , Anemia Aplástica/epidemiologia , Anemia Aplástica/metabolismo , Feminino , Citometria de Fluxo/métodos , Hemoglobinúria Paroxística/metabolismo , Humanos , Masculino , Síndromes Mielodisplásicas/epidemiologia , Síndromes Mielodisplásicas/metabolismo , Prevalência , Estudos Prospectivos , Estudos Retrospectivos
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