Clinical, Immunological and Molecular Characteristics of 37 Iranian Patients with X-Linked Agammaglobulinemia

Aghamohammadi, Asghar; Fiorini, Maurilia; Moin, Mostafa; Parvaneh, Nima; Teimourian, Shahram; Yeganeh, Mehdi; Goffi, Francesca; Kanegane, Hirokazu; Amirzargar, Ali Akbar; Pourpak, Zahra; Rezaei, Nima; Salavati, Ali; Pouladi, Nima; Abdollahzade, Sina; Notarangelo, Luigi D.; Miyawaki, Toshio; Plebani, Alessandro

doi:10.1159/000095469

Cited by 50 publications

(38 citation statements)

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“…In our study, the rates of XLA increased, as the age at presentation increased. Bruton agammaglobulinemia is frequently manifested with recurrent lung infections, otitis media, sinusitis and gastrointestinal infections after the age of one year (15,16).…”

Section: Discussionmentioning

confidence: 99%

Profile of the patients who present to immunology outpatient clinics because of frequent infections

et al. 2014

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Aim: We aimed to determine the rate of primary immune deficiency (PID) among children presenting to our immunology outpatient clinic with a history of frequent infections and with warning signs of primary immune deficiency. Material and Methods:The files of 232 children aged between 1 and 18 years with warning signs of primary immune deficiency who were referred to our pediatric immunology outpatient clinic with a complaint of frequent infections were selected and evaluated retrospectively. Results: Thirty-six percent of the subjects were female (n=84) and 64% were male (n=148). PID was found in 72.4% (n=164). The most common diagnosis was selective IgA deficiency (26.3%, n=61). The most common diseases other than primary immune deficiency included reactive airway disease and/or atopy (34.4%, n=22), adenoid vegetation (12.3%, n=8), chronic disease (6.3%, n=4) and periodic fever, aphtous stomatitis and adenopathy (4.6%, n=3). The majortiy of the subjects (90.5%, n=210) presented with a complaint of recurrent upper respiratory tract infection. PID was found in all subjects who had bronchiectasis. The rates of the diagnoses of variable immune deficiency and Bruton agammaglubulinemia (XLA) were found to be significantly higher in the subjects who had lower respiratory tract infection, who were hospitalized because of infection and who had a history of severe infection compared to the subjects who did not have these properties (p<0.05 and p<0.01, respectively). Growth and developmental failure was found with a significantly higher rate in the patients who had a diagnosis of severe combined immune deficiency or hyper IgM compared to the other subjects (p<0.01). No difference was found in the rates of PID between the age groups, but the diagnosis of XLA increased as the age of presentation increased and this was considered an indicator which showed that patients with XLA were being diagnosed in a late period. Conclusions: It was found that the rate of diagnosis was considerably high (72.4%), when the subjects who had frequent infections were selected by the warning signs of PID. (Türk Ped Arş 2014; 49: 210-6)

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Section: Discussionmentioning

confidence: 99%

Profile of the patients who present to immunology outpatient clinics because of frequent infections

et al. 2014

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“…Mutation analysis studies were performed as part of the routine investigation to exclude other causes of hypogammaglobulinemia. For patients with B-cell populations of Ͻ1% of the total lymphocyte count who exhibited agammaglobulinemia with low numbers of B cells (X linked and autosomal recessive), mutation analysis of candidate genes (e.g., BTK) was performed (2). The patients with normal B-cell populations were genotyped at SH2D1A to exclude X-linked lymphoproliferative syndrome.…”

Section: Methodsmentioning

confidence: 99%

Serum Bactericidal Antibody Responses to Meningococcal Polysaccharide Vaccination as a Basis for Clinical Classification of Common Variable Immunodeficiency

Rezaei

Aghamohammadi

Siadat

et al. 2008

Clin Vaccine Immunol

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Common variable immunodeficiency (CVID) is a heterogeneous group of disorders characterized by hypogammaglobulinemia and increased susceptibility to recurrent pyogenic infections. This study was performed to subclassify CVID on the basis of the bactericidal antibody responses of patients to polysaccharide meningococcal vaccine. Twenty-five patients with CVID (18 male and 7 female) and 25 healthy volunteers received meningococcal polysaccharide vaccine A ؉ C. Serum bactericidal antibody (SBA) titers were measured at baseline and after 3 weeks. Response was correlated with clinical and immunological manifestations of CVID. Twenty-four (96%) of the 25 normal controls had a protective SBA titer of >8 postvaccination, whereas only 16 (64%) of the 25 CVID patients had a protective titer (P value ‫؍‬ 0.013). Among the patients with CVID who were nonresponders, there were significantly increased rates of bronchiectasis (P ‫؍‬ 0.008), splenomegaly (P ‫؍‬ 0.016), and autoimmunity (P ‫؍‬ 0.034) in comparison with patients who had protective SBA titers. A reversed CD4/CD8 ratio was more common in the nonresponder group of patients (P ‫؍‬ 0.053). We conclude that individuals with CVID who cannot produce protective postvaccination titers after receiving meningococcal polysaccharide vaccine are more likely to exhibit bronchiectasis, splenomegaly, and autoimmune diseases. Vaccination response may define subgroups of patients with CVID, enabling more effective monitoring and therapeutic strategies.Common variable immunodeficiency (CVID) is the most common symptomatic antibody deficiency and is characterized by hypogammaglobulinemia in the absence of any recognized genetic abnormality (8,13,21). CVID patients are susceptible to recurrent pyogenic infections (1, 8), as well as autoimmune and neoplastic diseases (6,17). Although infections of the respiratory and gastrointestinal tracts are common, some patients may present with meningitis (1, 8). Encapsulated organisms such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis are the most prominent pathogens in CVID patients (13,26).Despite attempts during recent decades to identify the underlying immune system defects in CVID, the pathogenesis of CVID remains unknown (26). Thus, the diagnosis of CVID is based on the genetic exclusion of other hypogammaglobulinemias that are well defined at the molecular level (11). Although the underlying pathophysiology of CVID is not clearly understood, a few general defects that lead to alteration of serum immunoglobulin concentrations have been described. Patients with CVID have a defect in B-cell differentiation that leads to impaired secretion of immunoglobulins. Additionally, several abnormalities of T cells have been reported in some patients (26).It has recently been shown that patients with CVID with loss of immunoglobulin M (IgM) memory B cells are susceptible to earlier onset of recurrent infections and more severe complications (5) than those with mild to moderate clinical manifestations. A number of other i...

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“…BTK kinase domain is activated by Y551 phosphorylation at activation loop. Variation Y551H inactivates the protein by preventing activation although the protein is expressed (Aghamohammadi et al 2006). T168N substitution leads to "generation of novel posttranslational modification site", a new N-glycosylation site, to interferon receptor IFNγR2 causing severe mycobacterial disease (Vogt et al 2005).…”

Section: Effect On Post Translational Modificationmentioning

confidence: 99%

Types and effects of protein variations

Vihinen

2015

Hum Genet

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Types and effects of protein variations. Vihinen, MaunoPublished in: Human Genetics DOI: 10.1007/s00439-015-1529-6Published: 2015-01-01Link to publication Citation for published version (APA): Vihinen, M. (2015). Types and effects of protein variations. Human Genetics, 134(4), 405-421. DOI: 10.1007405-421. DOI: 10. /s00439-015-1529 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. for all variation types, a more detailed description can be made by explaining changes to protein function, structure and properties. Examples are provided for the effects and mechanisms, usually in relation to human diseases. In addition, the examples are selected so that protein 3D structural changes, when relevant, are included and visualized. Here, systematics is described for protein variants based on VariO. It will benefit the unequivocal description of variations and their effects and further reuse and integration of data from different sources. 1 TYPES AND EFFECTS OF PROTEIN VARIATIONS

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Clinical, Immunological and Molecular Characteristics of 37 Iranian Patients with X-Linked Agammaglobulinemia

Cited by 50 publications

References 47 publications

Profile of the patients who present to immunology outpatient clinics because of frequent infections

Profile of the patients who present to immunology outpatient clinics because of frequent infections

Serum Bactericidal Antibody Responses to Meningococcal Polysaccharide Vaccination as a Basis for Clinical Classification of Common Variable Immunodeficiency

Types and effects of protein variations

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