Browsing by Author "Borrego, LM"
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- Added value of lymphocyte subpopulations in the classification of Sjögren's syndromePublication . Barcelos, F; Brás-Geraldes, C; Martins, C; Papoila, AL; Monteiro, R; Cardigos, J; Madeira, N; Alves, N; Vaz-Patto, J; Cunha-Branco, J; Borrego, LMSjögren's Syndrome (SjS) is a chronic systemic immune-mediated inflammatory disease characterized by lymphocytic infiltration and consequent lesion of exocrine glands. SjS diagnosis and classification remains a challenge, especially at SjS onset, when patients may have milder phenotypes of the disease or uncommon presentations. New biomarkers are needed for the classification of SjS, thus, we aimed to evaluate the added-value of lymphocyte subpopulations in discriminating SjS and non-Sjögren Sicca patients. Lymphocyte subsets from 62 SjS and 63 Sicca patients were characterized by flow cytometry. The 2002 AECG and the 2016 ACR/EULAR SjS classification criteria were compared with clinical diagnosis. The added discriminative ability of joining lymphocytic populations to classification criteria was assessed by the area under the Receiver-Operating-Characteristic Curve (AUC). Considering clinical diagnosis as the gold-standard, we obtained an AUC = 0.952 (95% CI: 0.916-0.989) for AECG and an AUC = 0.921 (95% CI: 0.875-0.966) for ACR/EULAR criteria. Adding Tfh and Bm1 subsets to AECG criteria, performance increased, attaining an AUC = 0.985 (95% CI: 0.968-1.000) (p = 0.021). Th1/Breg-like CD24hiCD27+ and switched-memory B-cells maximized the AUC of ACR/EULAR criteria to 0.953 (95% CI: 0.916-0.990) (p = 0.043). Our exploratory study supports the potential use of lymphocyte subpopulations, such as unswitched memory B cells, to improve the performance of classification criteria, since their discriminative ability increases when specific subsets are added to the criteria.
- Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitisPublication . Barcelos, F; Martins, C; Monteiro, R; Cardigos, J; Prussiani, T; Sítima, M; Alves, N; Vaz-Patto, JA; Cunha-Branco, J; Borrego, LMSjögren's syndrome (SjS) is characterized by lymphocytic infiltration of exocrine glands, i.e. autoimmune epithelitis. Lymphocytes are central in SjS pathogenesis, with B-cell hyperactivity mediated by T-cells. B-cells are main targets of Epstein-Barr virus (EBV) infection, a frequently-suggested trigger for SjS. We aimed to evaluate how the EBV infection modulates B and T-cell subsets in SjS, including as controls Rheumatoid arthritis patients (RA) and healthy participants (HC). SjS patients presented decreased CXCR5+T-cells, although IL21-secreting Tfh and Tfc cells were increased. Tfc were positively correlated with ESSDAI scores, suggesting their relevant role in SjS pathogenesis. As previously described, SjS patients showed expanded circulating naïve B-cell compartments. SjS patients had a higher incidence of EBV-EA-D-IgG+ antibodies, characteristic of recent EBV-infection/reactivation. SjS patients with past infection or recent infection/reactivation showed increased CXCR3+Th1 and CXCR3+Tfh1 cells compared to those without active infection. SjS patients with a recent infection/reactivation profile presented increased transitional B-cells compared to patients with past infection and increased plasmablasts, compared to those without infection. Our results suggest EBV-infection contributes to B and T-cell differentiation towards the effector phenotypes typical of SjS. Local lymphocyte activation at ectopic germinal centres, mediated by Tfh and Tfc, can be EBV-driven, perpetuating autoimmune epithelitis, which leads to gland destruction in SjS.
- Characterization of B cells in healthy pregnant women from late pregnancy to post-partum: a prospective observational studyPublication . Lima, J; Martins, C; Leandro, MJ; Nunes, G; Sousa, MJ; Branco, JC; Borrego, LMAbstract BACKGROUND: B cells play a role in pregnancy due to their humoral and regulatory activities. To our knowledge, different maturational stages (from transitional to memory) of circulating B cell subsets have not yet been characterized (cell quantification and phenotype identification) in healthy pregnant women. Thus, the objective of our study was to characterize these subsets (as well as regulatory B cells) from late pregnancy to post-partum and to compare them with the circulating B cells of non-pregnant women. METHODS: In all of the enrolled women, flow cytometry was used to characterize the circulating B cell subsets according to the expression of IgD and CD38 (Bm1-Bm5 classification system). Regulatory B cells were characterized based on the expression of surface antigens (CD24, CD27, and CD38) and the production of IL-10 after lipopolysaccharide stimulation. RESULTS: Compared to the absolute counts of B cells in the non-pregnant women (n = 35), those in the pregnant women (n = 43) were significantly lower (p < 0.05) during the 3rd trimester of pregnancy and on delivery day (immediately after delivery). The percentages of these cells on delivery day and at post-partum were significantly lower than those in the non-pregnant women. In general, the absolute counts and percentages of the majority of the B cell subsets were significantly lower in the 3rd trimester of pregnancy and on delivery day than in the non-pregnant women. However, these counts and percentages did not differ significantly between the post-partum and the non-pregnant women. The most notable exceptions to the above were the percentages of naïve B cells (which were significantly higher in the 3rd trimester and on delivery day than in the non-pregnant women) and of CD24(hi)CD38(hi) regulatory B cells (which were significantly higher in the post-partum than in the non-pregnant women). CONCLUSION: According to our study, the peripheral B cell compartment undergoes quantitative changes during normal late pregnancy and post-partum. Such findings may allow us to better understand immunomodulation during human pregnancy and provide evidence that could aid in the development of new strategies to diagnose and treat pregnancy-associated disturbances. Our findings could also be useful for studies of the mechanisms of maternal responses to vaccination and infection.
- Characterization of B cells in healthy pregnant women from late pregnancy to post-partum: a prospective observational studyPublication . Lima, J; Martins, C; Leandro, MJ; Nunes, G; Sousa, MJ; Branco, JC; Borrego, LMBACKGROUND: B cells play a role in pregnancy due to their humoral and regulatory activities. To our knowledge, different maturational stages (from transitional to memory) of circulating B cell subsets have not yet been characterized (cell quantification and phenotype identification) in healthy pregnant women. Thus, the objective of our study was to characterize these subsets (as well as regulatory B cells) from late pregnancy to post-partum and to compare them with the circulating B cells of non-pregnant women. METHODS: In all of the enrolled women, flow cytometry was used to characterize the circulating B cell subsets according to the expression of IgD and CD38 (Bm1-Bm5 classification system). Regulatory B cells were characterized based on the expression of surface antigens (CD24, CD27, and CD38) and the production of IL-10 after lipopolysaccharide stimulation. RESULTS: Compared to the absolute counts of B cells in the non-pregnant women (n = 35), those in the pregnant women (n = 43) were significantly lower (p < 0.05) during the 3rd trimester of pregnancy and on delivery day (immediately after delivery). The percentages of these cells on delivery day and at post-partum were significantly lower than those in the non-pregnant women. In general, the absolute counts and percentages of the majority of the B cell subsets were significantly lower in the 3rd trimester of pregnancy and on delivery day than in the non-pregnant women. However, these counts and percentages did not differ significantly between the post-partum and the non-pregnant women. The most notable exceptions to the above were the percentages of naïve B cells (which were significantly higher in the 3rd trimester and on delivery day than in the non-pregnant women) and of CD24(hi)CD38(hi) regulatory B cells (which were significantly higher in the post-partum than in the non-pregnant women). CONCLUSION: According to our study, the peripheral B cell compartment undergoes quantitative changes during normal late pregnancy and post-partum. Such findings may allow us to better understand immunomodulation during human pregnancy and provide evidence that could aid in the development of new strategies to diagnose and treat pregnancy-associated disturbances. Our findings could also be useful for studies of the mechanisms of maternal responses to vaccination and infection.
- Feasibility of routine respiratory function testing in preschool childrenPublication . Santos, N; Almeida, I; Couto, M; Morais-Almeida, M; Borrego, LMINTRODUCTION: The assessment of respiratory function in preschool children, which has recently been attracting considerable interest, has several methodological particularities. Whether this is feasible in clinical practice with large groups of patients still needs to be investigated. AIM: To assess the feasibility of pulmonary function testing in preschool children in clinical practice, and report the degree of success achieved according to age. METHODS: Retrospective analysis of lung function tests performed in children from 2 to 6 years old at the respiratory function laboratory of CUF Descobertas Hospital between September 2006 and August 2011. Whole-body pletismography without occlusion for specific airway resistance (sRaw) assessment and animated spirometry were performed using the equipment Jaeger 4.65 (Viasys Healthcare), before and after 400 μg of inhaled salbutamol via a spacer device. The research fulfilled international criteria (ATS/ERS) for acceptability and reproducibility. RESULTS: Of 1,239 lung function tests performed, 1,092 (88%) had acceptable and reproducible criteria for spirometry (children with a mean age of 4.3±0.91 years; 60.7% male), and 979 (79%) for sRaw measurement. We were able to report FEV(1) in 801 (65%) tests (children with a mean age of 4.5±0.89 years). In 23 (2%) tests it was only possible to report FEV(0.5) (children with a mean age of 3.5±0.67 years) and in 268 (22%) only FEV(0.75) (children with a mean age of 4.0±0.89 years). CONCLUSION: Spirometry and sRaw assessment in preschool children can be used in clinical practice, with an increasing success rate as children get older. Reporting maneuvers of 0.5 or 0.75 seconds facilitates spirometric evaluation in a larger number of children.
- Regulatory T and B cells in asthmatic women: variations from pregnancy to postpartum Treg and Breg: pregnancy to postpartumPublication . Martins, C; Lima, J; Nunes, G; Borrego, LMBACKGROUND: Allergic asthma and rhinitis are common in pregnancy. The immune mechanisms underlying the effects of pregnancy in asthma and vice-versa are not completely understood. OBJECTIVES: This work aimed to study the evolution of regulatory T and B cells in asthmatic pregnant women, from late pregnancy till postpartum. METHODS: Four groups of women were enrolled for this study: third trimester pregnant women, asthmatic (n=24) and healthy (n=43), and non-pregnant women, asthmatic (n=33) and healthy (n=35). Pregnant women were also evaluated postpartum (>6 weeks after delivery). Blood samples were taken from each woman and flow cytometry was used to characterize circulating regulatory T and B cells. Foxp3 expression was assessed within CD4DimCD25Hi regulatory T cells. RESULTS: In asthmatic and healthy pregnant women, regulatory T cells did not oscillate significantly from pregnancy to postpartum, but CD24HiCD38Hi regulatory B cells, decreased in pregnancy, rose significantly postpartum. Foxp3 expression in regulatory T cells was also impaired during pregnancy in asthmatic and healthy pregnant women, recovering postpartum. Nevertheless, asthmatic pregnant women presented higher Foxp3 expression than healthy pregnant women (p=0.007), probably due to the use of control medication. CONCLUSIONS: Women with controlled asthma present variations in regulatory cell subsets during pregnancy and postpartum. The similar pattern observed for Foxp3 expression and CD24HiCD38Hi regulatory B cells during this period corroborates the interaction established between regulatory T and B cells in immune responses. Considering the immunomodulatory potential of these immune mediators, more studies are needed to evaluate their relation with asthma and rhinitis complications in pregnancy.
- Roles of interleukin-17 in uveitisPublication . Guedes, MC; Borrego, LM; Proença, RDTh17 cells, a CD4+ T-cell subset, produce interleukin (IL)-17, a pro-inflammatory cytokine that has been shown to be involved in several forms of infectious and noninfectious uveitis. Here, we explore the roles of this IL in uveitic disorders as well as in experimental autoimmune uveitis, the possible pathogenic implications of several cytokines associated with IL-17 and analyze the current outcomes and goals for drugs aiming for the IL-17 pathway.
- Serum markers of B-cell activation in pregnancy during late gestation, delivery, and the postpartum periodPublication . Lima, J; Cambridge, G; Vilas-Boas, A; Martins, C; Borrego, LM; Leandro, MB cells are vital for the normal evolution of pregnancy due to their humoral and possible regulatory activities. Our group and others have documented that circulating B-cell subsets undergo changes from normal late pregnancy to the postpartum period. However, the underlying mechanisms are poorly understood. Therefore, this study examined the degree of B-cell activation in normal pregnancy by analyzing the levels of serum markers in healthy pregnant women during the third trimester of pregnancy, the day of delivery, and the postpartum period. METHOD OF STUDY: A prospective study including pregnant and non-pregnant women attending routine care was undertaken at a hospital clinic. Sociodemographic and clinical data were collected, along with peripheral blood samples. The serum levels of soluble CD23 (sCD23), B-cell-activating factor (BAFF), kappa (κ) and lambda (λ) free light chains (FLC), IgA, IgG, and IgM were quantified. RESULTS: Our study included 43 third trimester pregnant and 35 non-pregnant women. In the pregnant women, the median levels of sCD23, BAFF, IgG, and κ FLC were significantly higher during the postpartum period than during the third trimester of pregnancy. Compared to the non-pregnant women, the third trimester pregnant women had higher median BAFF levels and lower sCD23, IgA, IgG, and FLC levels. CONCLUSION: Changes in serum markers of B-cell kinetics that occur during pregnancy often persist into the postpartum period and affect the secretion of immunoglobulins from different classes. Further studies are needed to clarify the biological significance of our observations.
- Successful oral tolerance induction to cow's milk in a child with allergy to extensively hydrolysed formulaPublication . Santos, N; Gaspar, A; Borrego, LM; Morais-Almeida, M
- The need for patient-focused therapy for children and teenagers with allergic rhinitis: a case-based review of current European practice.Publication . Santos, AF; Borrego, LM; Rotiroti, G; Scadding, G; Roberts, GAllergic rhinitis is a common problem in childhood and adolescence, with a negative impact on the quality of life of patients and their families. The treatment modalities for allergic rhinitis include allergen avoidance, anti-inflammatory symptomatic treatment and allergen specific immunotherapy. In this review, four cases of children with allergic rhinitis are presented to illustrate how the recently published EAACI Guidelines on Pediatric Allergic Rhinitis can be implemented in clinical practice.