Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

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.

Common 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 γδ 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 γδ T cells and CVID patients were compared to healthy controls (n = 22). The frequency and absolute count of Vδ1 γδ 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 Vδ2 γδ 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 Vδ1 to Vδ2 ratio (0.24 vs 1.4, P <0.001). Markers of immune activation were elevated on all subsets of γδ T cells, and HLA-DR expression was associated with an expansion of Vδ1 γδ T cells (r = 0.73, P = 0.003). Elevated PD-1 expression was found only on Vδ2 γδ T cells (median 1.15% vs 3.08%, P <0.001) and was associated with the decrease of Vδ2 γδ T cells (r = -0.67, P = 0.007). IVIg had no effect on the frequency of Vδ1 and Vδ2 γδ T cells or HLA-DR expression, but alleviated CD38 expression on Vδ1 γδ T cells (median MFI 965 vs 736, P <0.05). These findings suggest that immunological perturbations of γδ T cells are a general feature associated with CVID and are only partially reversed by IVIg therapy.

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 patient's 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.

Avaliação da resposta clínica dos pacientes com imunodeficiência comum variável submetidos à vacinação com antígenos proteicos e polissacarídicos / Clinical evaluation of patients with common variable immunodeficiency before and after immunization with polysaccharide and protein antigens

OBJETIVO: Avaliar a resposta clínica a imunização com antígenos proteicos e polissacarídicos após administração de vacinas de antígenos específicos (Pneumococo e Influenza H2N3 e H1N1) em pacientes com imunodeficiência comum variável (ICV) acompanhados no ambulatório de Imunodeficiências Primáriasdo Serviço de Imunologia Clínica e Alergia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP). MÉTODOS: Os pacientes foram diagnosticados segundo critérios da OMS, PAGID e ESID. Os pacientes foram vacinados contra Influenza H2N3, Influenza H1N1 e Pneumococo. A avaliação clínica foi realizada a partir de um escore clínico no qual os parâmetros considerados foram: pneumonias, sinusites, otite média aguda, infecções de vias aéreas superiores virais (IVAS), amigdalite, diarreia, bronquiectasias, hospitalizações, uso de antibiótico terapêutico, uso de antibiótico profilático, sepse e meningite. Avaliação do escore clínico foi realizada durante o ano que precedeu a vacinação e um ano após a administração das vacinas. RESULTADOS: Participaram do estudo 45 pacientes (51% mulheres), com idade entre 20 a 78 anos (média 36,3 anos). Observamos mediana de 7 anos de retardo no diagnóstico dos pacientes com ICV. IVAS, pneumonias e sinusites foram as manifestações infecciosas mais frequentes em mulheres (80%, 78% e 55% respectivamente). IVAS, sinusites e pneumonias foram os achados mais frequentes em homens (78%, 65% e 35% respectivamente). Houve redução significativa do escore clínico em relação ao número de sinusites e IVAS após a administração das vacinas (p < 0,001).CONCLUSÕES: Observamos redução do número de infecções, especialmente sinusites e IVAS no ano posterior à vacinação. Esta observação reforça o benefício da vacinação e sugere modificação na orientação quanto às indicações de vacinas nos pacientes com ICV.

Objective: To evaluate clinical response to immunization with polysaccharide and protein antigens following administration of specific antigen vaccines (Pneumococcus and Influenza H2N3 and H1N1) in patients with common variable immunodeficiency (CVID) treated at the Primary Immunodeficiency Outpatient Clinic of the Division of Clinical Immunology and Allergy at the Clinical Hospital of the School of Medicine of University of São Paulo (HC-FMUSP). Methods: Patients were diagnosed according to WHO, PAGID, and ESID criteria. Patients were vaccinated against Influenza H2N3, Influenza H1N1, and Pneumococcus. Clinical evaluation was performed using clinical scores for the following parameters: pneumonia, sinusitis, acute otitis media, viral upper respiratory tract infections (URI), tonsillitis, diarrhea, bronchiectasis, hospitalizations, antibiotic therapy, antibiotic prophylaxis, sepsis, and meningitis. Evaluation focused on one year prior to immunization and one year after the administration of vaccines. Results: A total of 45 patients (51% women), aged 20 to 78 years (mean 36.3 years), were evaluated. A median delay of 7 years was observed in the diagnosis of patients with CVID. URI, pneumonia, and sinusitis were the most frequent infectious conditions found in women (80%, 78%, and 55%, respectively); URI, sinusitis, and pneumonia were the most frequent findings in men (78%, 65%, and 35%, respectively). There was a significant reduction in the clinical scores assigned to the number of sinusitis and URI episodes following administration of the vaccines (p < 0.001). Conclusions: A reduction was observed in the number of infections, particularly sinusitis and URI, in the year following immunization. This finding reinforces the benefit of vaccination and suggests modifications to current recommendations for vaccines in patients with CVID.

Papel da imunoglobina intravenosa na asma brônquica / Role of intravenous immunoglobulin in bronchial asthma

Há mais de 20 anos a imunoglobulina humana exógena vem sendo aplicada, principalmente por via intravenosa (IgIV), em diferentes doenças e com diferentes funções, na prática clínica. Classicamente era usada apenas em iunodeficiências primárias, mas outros benefícios dessa medicação foram documentados em outras doenças imuno-inflamatórias, tais como, doença de Kawasaki e púrpura trombocitopênica idiopática. Alguns autores passaram então a aplicar IgIV em pacientes com asma de difícil controle, corticosteróide dependente, e obtiveram resultados interessantes, no entanto, trabalhos duplo-cegos, randomizados e controlados falharam em mostrar o benefício dessa medicação na asma grave. Descrevemos neste artigo alguns aspectos sobre as indicações de IgIV e aspectos importantes na abordagem da asma de difícil controle. Revisamos os principais trabalhos publicados sobre a aplicação de IgIV na asma brônquica, incluindo fatores imunopatológicos implicados e possíveis mecanismos de ação da medicação na doença.

Immunoglobulin has been used in medicine for more than twenty years. Initially, it was administered mainly to primary immunodeficiencies patients, but late r was also demonstrated benefits in inflammatory diseases, like Kawasaki Disease and thrombocytopenic purpura. Some physicians started to use it in difficult to contrai asthma with interesting results. However, there is not large, randomized, placebo-controlled and doubleblind studies supporting the efficacy of intravenous gammaglobulin in asthma. This study reviews the literature and discusses intravenous gammaglobulin indications in the treatment of difficult to contrai asthma and its possible mechanisms of action.

Clinical and laboratory aspects of common variable immunodeficiency

A imunodeficiência comum variável (CVID) é uma doença caracterizada por hipogamaglobulinemia, infecções recorrentes, especialmente das vias aéreas, enfermidades auto-imunes e neoplasias. Alguns pacientes com CVID possuem diversos distúrbios do sistema imune como alterações no número e proporção de diferentes populações leucocitárias; resposta proliferativa linfocitária diminuída para antígenos e mitógenos; produção alterada de citocinas e alteração na expressão de moléculas de superfície. Neste trabalho, são discutidas várias destas alterações imunológicas procurando correlacioná-las aos achados clínicos dos pacientes e incorporar aos dados da literatura os nossos próprios achados.

Clinical and laboratory aspects of common variable immunodeficiency.

Common variable immunodeficiency (CVID) is an immunological disorder characterized by defective antibody production, recurrent infections, most notably of the respiratory tract, autoimmune phenomena and cancer. Some CVID patients may also present disturbances of the cellular immune response such as a decrease in the number and proportion of different lymphocyte populations, diminished lymphoproliferative response to mitogens and antigens, altered production of cytokines, and deficient expression of cell-surface molecules. Most Brazilian CVID patients included in this study show a decrease in T and B lymphocyte counts in the peripheral blood. Furthermore, their lymphocytes are more susceptible to apoptosis following activation than normal individuals, and they have a decrease in the expression of activation molecules like CD25, CD69, CD40L and CD70. Moreover, they show a decreased synthesis of IL-4 and IL-5 in comparison with normal individuals. The increase in susceptibility to apoptosis following activation, may also be responsible for the decrease in the expression of activation molecules and CD40L, decrease in Th2 cytokines synthesis, and in the number of T and B circulating cells. In this study we discuss some of these immunological disturbances correlating them to the patients' clinical features and comparing our patients' findings to the literature.