Background The number of inherited diseases and the spectrum of clinical manifestations of primary immunodeficiency disorders (PIDs) are ever-expanding. Molecular diagnosis using genomic approaches should be performed for all PID patients since it provides a resource to improve the management and to estimate the prognosis of patients with these rare immune disorders. Method The current update of Iranian PID registry (IPIDR) contains the clinical phenotype of newly registered patients during last 5 years (2013-2018) and the result of molecular diagnosis in patients enrolled for targeted and nextgeneration sequencing. Results Considering the newly diagnosed patients (n = 1395), the total number of registered PID patients reached 3056 (1852 male and 1204 female) from 31 medical centers. The predominantly antibody deficiency was the most common subcategory of PID (29.5%). The putative causative genetic defect was identified in 1014 patients (33.1%) and an autosomal recessive pattern was found in 79.3% of these patients. Among the genetically different categories of PID patients, the diagnostic rate was highest in defects in immune dysregulation and lowest in predominantly antibody deficiencies and mutations in the MEFV gene were the most frequent genetic disorder in our cohort.

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It is important that non-immunologist physicians be alert of the associated autoimmunity with PADs in order to reduce the diagnostic delay and establish timely immunoglobulin replacement therapy in these patients.

LRBA deficiency has a very broad and variable phenotype and should be considered, especially in children with early-onset hypogammaglobulinemia, severe autoimmune manifestations, enteropathy, lymphoproliferation, and recurrent respiratory tract infections.

Common variable immunodeficiency (CVID) is the most common clinical primary immunodeficiency. It is characterized by a defect in B-cell differentiation to plasma and memory B cells. Moreover, numerous T-cell abnormalities have been reported and include decreased T-cell count and proliferative response, increased T-cell activation and apoptosis, and abnormalities in cytokine production. The aims of this review are to describe phenotypic and functional defects in T cells in CVID patients and to review the literature with respect to the effects of immunoglobulin replacement on the T-cell component in CVID patients. Key words: Common variable immunodeficiency. T cell. Helper T cells. Regulatory T cells. ResumenLa inmunodeficiencia común variable (CVID) es la inmunodeficiencia primaria más frecuente. Se caracteriza por un defecto en la diferenciación de linfocitos B hacia células plasmáticas y linfocitos B memoria. Se han descrito numerosas alteraciones en los linfocitos T de estos pacientes, tales como disminución en el número de linfocitos T y en sus respuestas proliferativas, aumento en la activación de células T y en la apoptosis, así como alteraciones en la producción de citokinas. El objetivo de esta revisión es describir las alteraciones funcionales y fenotípicas de los linfocitos T en los pacientes con CVID y revisar la bibliografía en relación a los efectos que la administración de inmunoglobulinas produce en los linfocitos T de los pacientes con CVID. Palabras clave: Inmunodeficiencia común variable. Células T. Células T helper. Células T reguladoras.

Common variable immunodeficiency (CVID) is a diagnostic category of primary immunodeficiency (PID) which may present with heterogeneous disorders including recurrent infections, autoimmunity, granulomatous diseases, lymphoid and other types of malignancies. Generally, the incidence of malignancy in CVID patients is around 1.5-20.7% and usually occurs during the 4th-6th decade of life. Non-Hodgkin lymphoma is the most frequent malignancy, followed by epithelial tumours of stomach, breast, bladder and cervix. The exact pathological mechanisms for cancer development in CVID are not fully determined; however, several mechanisms including impaired genetic stability, genetic predisposition, immune dysregulation, impaired clearance of oncogenic viruses and bacterial infections, and iatrogenic causes have been proposed to contribute to the high susceptibility of these patients to malignancies.

IntroductionPrimary immunodeficiency diseases (PIDs) are a heterogeneous group of genetic immune disorders. PID patients suffer from a variety of complications. The aim of this study was to determine the infectious and non-infectious complications among PID patients.Material and methodsThis retrospective cohort study was performed on recorded data of 202 PID patients who were diagnosed with eight major categories: common variable immunodeficiency (CVID), X-linked agammaglobulinemia, hyper-IgM syndrome, hyper IgE syndrome, chronic granulomatous disease (CGD), ataxia telangiectasia, hereditary angioedema and leukocyte adhesion deficiency. For all patients, infectious and non-infectious manifestations and laboratory data were collected in a comprehensive questionnaire.ResultsInfectious complications were more frequent than non-infectious complications. Pneumonia and otitis media were the main infectious problems in PID patients, especially in patients with antibody deficiencies. Among the non-infectious complications, splenomegaly and hepatomegaly were the most common complications in PID patients, and were more commonly seen in CGD patients than others. Splenomegaly, hepatomegaly and autoimmunity were the most common findings in CVID patients. A significant correlation was observed between diagnostic delay and bronchiectasis in CVID patients (p = 0.042).ConclusionsPID patients are at risk of multiple infectious and non-infectious problems. Timely diagnosis of PIDs not only improves their outcome and quality of life, but also helps prevent these troubling complications.

Autoimmunity may be the first clinical manifestation of CVID, thus routine screening of immunoglobulins is suggested for patients with autoimmunity. Lack of SAR in CVID is associated with the lack of specific autoantibodies in patients with autoimmunity. It is suggested that physicians use alternative diagnostic procedures.