Ana Karolina Barreto de Oliveira

IVIg Immune Reconstitution Treatment Alleviates the State of Persistent Immune Activation and Suppressed CD4 T Cell Counts in CVID

Common variable immunodeficiency (CVID) is characterized by defective B cell function, impaired antibody production, and increased susceptibility to bacterial infections. Here, we addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed CVID patients were sampled before, and 6–12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naïve CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory receptors CD80 and CD83 was elevated in mDCs and correlated with T cell activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was elevated. Importantly, immune reconstitution treatment with IVIg partially restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells and iNKT cells remained low. Thus, primary deficiency in humoral immunity with impaired control of microbial infections is associated with significant pathological changes in cell-mediated immunity. Furthermore, therapeutic enhancement of humoral immunity with IVIg infusions alleviates several of these defects, indicating a relationship between poor antibody-mediated immune control of infections and the occurrence of abnormalities in the T cell and mDC compartments. These findings help our understanding of the immunopathogenesis of primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1 infection.

Dysregulated CD1 profile in myeloid dendritic cells in CVID is normalized by IVIg treatment.

To the editor: The CD1 proteins are major histocompatibility complex class I-like molecules specialized in presenting lipid and glycolipid antigens to T cells.[1][1] Group I CD1s include CD1a, CD1b, and CD1c and present bacterial antigens to a diverse repertoire of pathogen-specific T cells.[2][2]

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.

B cell subtypes' kinetics over a 6 monthxs period in CVID patients submitted to influenza and H1N1 immunization

Background Common Variable Immunodeficiency (CVID) is characterized by hypogammaglobulinaemia and impaired specific antibody production, resulting in increased susceptibility to infections, mainly of the respiratory tract. In an attempt to minimize the recurrent episodes of infections, some studies have recommended immunization with inactivated pathogens or subunits, however, experience with vaccine administration in immunodeficient patients is limited.

Proteome-derived peptide library for the elucidation of the cleavage specificity of HF3, a snake venom metalloproteinase

The Proteomic Identification of Cleavage Sites (PICS) approach was employed for profiling the substrate specificity of HF3, a hemorrhagic snake venom metalloproteinase (SVMP) from Bothrops jararaca. A tryptic peptide library from human plasma was subject to HF3 cleavage and amino acid occurrence for P6 to P6′ sites was mapped. 71 cleavage sites were detected and revealed a clear preference for leucine at P1′ position, followed by hydrophobic residues in P2′. PICS confirmed existing data on prime site specificity of SVMPs.

Descriptive review of clinical data from 186 records of outpatients with IgA deficiency accompanied at a quaternary hospital in Brazil

Background IgA Deficiency (IgAD) is the most common immunoglobulin deficiency, with approximate incidence of 1 in 400 to 3000 individuals in general population. Selective IgA deficiency is defined as serum IgA levels less than 7 mg/dL with normal serum IgM and IgG levels. A subgroup of individuals, with more than 7 mg/dL but less than 30 mg/dL of serum IgA, are defined as partial IgA deficient patients (pIgAD). Many individuals with selective IgA deficiency are clinically asymptomatic. However, some patients have increased incidence of infections, mainly in respiratory and intestinal tracts, as well as presence of atopy, autoimmunity and cancer.

Undefined and fatal meningoenchephalitis in a patient with combined immune deficiency: a case report

Background Encephalitis is defined by the presence of brain inflammation associated with clinical evidence of neurological dysfunction. It can be due to infection (most common cause is viruses) or not (like post vaccine or auto immune). Primary immunodeficiency is defined as a genetic basis that leads any alteration in immune system (innate or adaptative) predisposing to infections, auto immunity and malignancies. Combined immunodefiency,alteration in T and B cell function, are potentially fatal disease.

Evaluation of TH17 profile in common variable immunodeficiency patients with or without autoimmunity

Background Common Variable Immunodeficiency (CVID) is the most common symptomatic primary antibody deficiency in clinical practice and it is characterized by hypogammaglobulinemia, increased susceptibility to infections, autoimmune diseases and malignancies. The pathogenesis of CVID is still not well established. Immunologic abnormalities found in CVID patients include defects in B cell differentiation, in T cell function, altered receptor expression and cytokine production, regulatory cell disturbances and disorders of innate immunity. The aim of this study was to evaluate the TH17 profile of CVID patients, in order to observe if CVID patients with autoimmunity present a TH17 polarized cellular response pattern.