Myrthes Toledo Barros

Allergic asthma in patients with common variable immunodeficiency

To cite this article: Agondi RC, Barros MT, Rizzo LV, Kalil J, Giavina‐Bianchi P. Allergic asthma in patients with common variable immunodeficiency. Allergy 2010; 65: 510–515.

IL-10-Producing Regulatory B Cells Are Decreased in Patients with Common Variable Immunodeficiency

Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency in adults. CVID patients often present changes in the frequency and function of B lymphocytes, reduced number of Treg cells, chronic immune activation, recurrent infections, high incidence of autoimmunity and increased risk for malignancies. We hypothesized that the frequency of B10 cells would be diminished in CVID patients because these cells play an important role in the development of Treg cells and in the control of T cell activation and autoimmunity. Therefore, we evaluated the frequency of B10 cells in CVID patients and correlated it with different clinical and immunological characteristics of this disease. Forty-two CVID patients and 17 healthy controls were recruited for this study. Cryopreserved PBMCs were used for analysis of T cell activation, frequency of Treg cells and characterization of B10 cells by flow cytometry. IL-10 production by sorted B cells culture and plasma sCD14 were determined by ELISA. We found that CVID patients presented decreased frequency of IL-10-producing CD24hiCD38hi B cells in different cell culture conditions and decreased frequency of IL-10-producing CD24hiCD27+ B cells stimulated with CpG+PIB. Moreover, we found that CVID patients presented lower secretion of IL-10 by sorting-purified B cells when compared to healthy controls. The frequency of B10 cells had no correlation with autoimmunity, immune activation and Treg cells in CVID patients. This work suggests that CVID patients have a compromised regulatory B cell compartment which is not correlated with clinical and immunological characteristics presented by these individuals.

Nephrotic syndrome associated with hepatointestinal schistosomiasis

Schistosomal nephropathy has long been related to the hepatosplenic form of schistosomiasis. In the last few years, 24 patients with hepatointestinal schistosomiasis and the nephrotic syndrome were studied. Aiming at evaluating a possible etiologic participation of schistosomiasis in the development of the nephropathy, this group was comparatively studied with a group of 37 patients with idiopathic nephrotic syndrome. Both groups had a different distribution of the histologic lesions. In the group with schistosomiasis there was a statistically significant prevalence of proliferative mesangial glomerulonephritis (33.3%), whereas in the control group there was prevalence of membranous glomerulonephritis (32.4%). On immunofluorescence, IgM was positive in 94.4% of the patients with schistosomiasis versus 55.0% in the control group (P < 0.01). In the group with schistosomiasis, 8 patients evidenced mesangial proliferative glomerulonephritis and 5, membranoproliferative glomerulonephritis. In both histological types immunofluorescence showed IgM and C3 granular deposits in the glomeruli. The data in this study suggests that mesangial proliferative and membranoproliferative glomerulonephritis, with glomerular granular IgM and C3 deposits, represent the renal lesions of the schistosomiasis associated nephropathy.

Can patients with common variable immunodeficiency have allergic rhinitis

Background Rhinosinusitis is highly prevalent in patients with common variable immunodeficiency (CVID), and probably allergic rhinitis (AR) may be masked by a history of repeated respiratory infections. The diagnosis of AR is based on the patients symptoms and detection of specific immunoglobulin E (IgE) to aeroallergens. This study was designed to identify rhinitis of probable allergic cause in patients with CVID. Methods This study included 72 adult CVID patients. The patients were divided into three groups according to their history: suggestive of AR, nonallergic rhinitis, and without rhinitis. They were tested for total and specific IgE (in vivo and in vitro). Results The patients’ mean age was 38.2 years. A history of chronic rhinitis was observed in 59 (81.9%) of the cases, 31 of which (43%) had a history suggestive of AR. Patients with a history of rhinitis (whether allergic or nonallergic) presented an earlier onset of symptoms and diagnosis of CVID. Total IgE was undetectable in 86.1% of patients. AR was confirmed by detection of specific IgE to aeroallergens in only 5.6% of the patients. Conclusion In CVID patients, chronic rhinitis may be allergic, because many have personal and family histories suggestive of atopy. However, in this study, allergy was confirmed by specific IgE detection in only 5.6% of cases. CVID patients with a history suggestive of AR commonly present negative results on traditional testing, so additional experiments may be necessary. One suggestion for the investigation of AR in CVID patients would be nasal provocation with the most prevalent allergens.

Loss of Circulating Mucosal-Associated Invariant T Cells in Common Variable Immunodeficiency Is Associated with Immune Activation and Loss of Eomes and PLZF

Common variable immunodeficiency (CVID) is characterized by low levels of Igs leading to increased risk of infections. Mucosal-associated invariant T (MAIT) cells are a recently identified population of innate T cells with potent antibacterial activity. We hypothesized that CVID is associated with alterations in MAIT cells. Cryopreserved PBMC from CVID patients and healthy controls were used to study the frequency, phenotype, and response to Escherichia coli stimulation of MAIT cells by flow cytometry. MAIT cell frequency and absolute counts were depressed in CVID. Residual MAIT presented elevated coexpression of CD38 and HLA-DR, and reduced expression of CCR6, whereas levels of CD127 (IL-7 receptor) were unchanged. CVID patients also had an accumulation of MAIT cells lacking the critical transcription factors eomesodermin and promyelocytic leukemia zinc finger protein. MAIT cell frequency was inversely associated with levels of soluble CD14, with coexpression of CD38 and HLA-DR, and accumulation of MAIT cells lacking eomesodermin or promyelocytic leukemia zinc finger protein expression. None of these changes were normalized by IgG replacement therapy. Finally, MAIT cells from CVID patients displayed poor IFN-γ responses to E. coli stimulation, in part due to defective Ag presentation, and these responses were increased by pretreatment with IL-7. Defective MAIT cell response may contribute to the increased incidence of microbial infections seen in CVID patients on IgG replacement therapy.

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies

RESUMO Nos ultimos anos, novas imunodeficiencias primarias e defeitos geneticos tem sido descritos. Recentemente, produtos de imunoglobulina, com aprimoramento em sua composicao e para uso por via subcutânea, tornaram-se disponiveis em nosso meio. Com o objetivo de orientar o medico no uso da imunoglobulina humana para o tratamento das imunodeficiencias primarias, os membros do Grupo de Assessoria em Imunodeficiencias da Associacao Brasileira de Alergia e Imunologia produziram um documento que teve por base uma revisao narrativa da literatura e sua [...]

Oral manifestations in patients with hypogammaglobulinemia

OBJECTIVE The overall objective of this study was to assess the oral manifestations and their association with immunologic status and health history, of individuals with hypogammaglobulinemia. STUDY DESIGN A case-controlled study of 100 subjects with hypogammaglobulinemia and 93 control individuals was performed. All participants were examined for dental caries, periodontal disease, mucosal lesions/infections, and general oral health problems. Decayed, missing, filled teeth and community periodontal index were recorded. Complete blood count, serum immunoglobulins, and lymphocyte immunophenotyping were measured on the same day of the oral health assessment. RESULTS Individuals with hypogammaglobulinemia showed higher prevalence of enamel hypoplasia and complaints of dry mouth, and lower prevalence of dental caries and periodontal disease. CONCLUSIONS The systemic conditions associated with hypogammaglobulinemia were not associated with enhanced susceptibility to caries, gingivitis, or periodontitis; however, individuals with hypogammaglobulinemia were more likely to report more episodes of recurrent aphthous ulcers compared with control individuals.

Inversion of the Vδ1 to Vδ2 γδ T cell ratio in CVID is not restored by IVIg and is associated with immune activation and exhaustion.

AbstractCommon variable immunodeficiency (CVID) is defined by low levels of IgG and IgA, but perturbations in T cells are also commonly found. However, there is limited information on &ggr;&dgr; T cells in CVID patients. Newly diagnosed CVID patients (n = 15) were enrolled before and after intravenous IgG (IVIg) replacement therapy. Cryopreserved peripheral blood mononuclear cells were then used to study &ggr;&dgr; T cells and CVID patients were compared to healthy controls (n = 22). The frequency and absolute count of V&dgr;1 &ggr;&dgr; T cells was found to be increased in CVID (median 0.60% vs 2.64%, P <0.01 and 7.5 vs 39, P <0.01 respectively), while they were decreased for V&dgr;2 &ggr;&dgr; T cells (median, 2.36% vs 0.74%, P <0.01 and 37.8 vs 13.9, P <0.01 respectively) resulting in an inversion of the V&dgr;1 to V&dgr;2 ratio (0.24 vs 1.4, P <0.001). Markers of immune activation were elevated on all subsets of &ggr;&dgr; T cells, and HLA-DR expression was associated with an expansion of V&dgr;1 &ggr;&dgr; T cells (r = 0.73, P = 0.003). Elevated PD-1 expression was found only on V&dgr;2 &ggr;&dgr; T cells (median 1.15% vs 3.08%, P <0.001) and was associated with the decrease of V&dgr;2 &ggr;&dgr; T cells (r = −0.67, P = 0.007). IVIg had no effect on the frequency of V&dgr;1 and V&dgr;2 &ggr;&dgr; T cells or HLA-DR expression, but alleviated CD38 expression on V&dgr;1 &ggr;&dgr; T cells (median MFI 965 vs 736, P <0.05). These findings suggest that immunological perturbations of &ggr;&dgr; T cells are a general feature associated with CVID and are only partially reversed by IVIg therapy.

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies (vol 15, pg 1, 2017)

[This corrects the article doi: 10.1590/S1679-45082017AE3844].

Comment to: II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies. einstein (Sao Paulo). 2017; 15(1): 1-16

Caro editor, Em relação ao “II Consenso Brasileiro sobre o uso de imunoglobulina humana em pacientes com imunodeficiências primárias”, publicado na revista einstein (São Paulo), em 2017, volume 15, numero 1,(1) gostaríamos de atualizar uma informação fornecida na página 6, a respeito do uso de imunoglobulina subcutânea facilitada pela hia luronidase. No momento da redação do texto, a informação, devidamente referenciada, era de que o produto não se encontrava aprovado em crianças e gestantes, mesmo nos países em que estava disponível comercialmente. No entanto, o produto está liberado na Europa para uso em crianças de qualquer idade desde julho de 2016.(2-4) O uso em gestantes ainda se encontra em investigação.(4) Consideramos relevante corrigir esta informação de maneira a garantir que o texto por nós redigido forneça as informações mais atualizadas possível, ao mesmo tempo que garantimos que os pacientes tenham acesso a mais este recurso terapêutico, assim que esta medicação seja liberada para uso em nosso meio.