Autoimmunity is observed by almost one-third of patients with (CVID). Different mechanisms including genetic defects and dysregulation of innate and adaptive immunity leads to autoimmunity in these patients (CVID). The clinical phenotypes of autoimmunity in (CVID) patients comprise fall in a wide spectrum, from organ-specific autoimmunity to systemic complications. The most COMMON autoimmunity is autoIMMUNE cytopenia in (CVID) patients. In this article, we have provided a collection of the most significant and recent information about prevalence, genetics, pathogenesis and clinical manifestations of autoimmunity in (CVID) patients, and provided an overview on its management and future perspective.

COMMON VARIABLE IMMUNE DEFICIENCY ((CVID)) is a heterogeneous syndrome with infective, autoIMMUNE and malignant manifestations. This study describes retrospectively the phenotyping and follow-up of the (CVID) patients in the allergy and clinical immunology department of Rasol E Akram Hospital of Iran University of Medical Sciences in Tehran until January 2014. The study included forty seven (CVID) patients with mean age at onset of symptoms and diagnosis of 11.2 and 20.2 years respectively. Phenotyping of our patients was: only infection (62%), cytopenia (26%) and PLI (19 %) and 94% of cases had only one phenotype. We did not find a significant relation between the clinical phenotypes and immunologic or demographic data. Rate of parental consanguinity in our cases was 47%. Parental consanguinity was related to lower age at onset, lower age at diagnosis and higher baseline IgG levels. Patients with malignancy and autoimmunity had significantly higher age at onset. Our patients were followed for 6.9 years and the mortality rate during this time was 6%.

(CVID) represents the most frequent symptomatic primary humoral immunoDEFICIENCY. Clinical presentation includes hypogammaglobulinemia, recurrent infections, autoIMMUNE phaenomena and increased lymphoma and cancer risk. While the first cases were reported in the early 50’ s, the first genetic cause of (CVID) was described after 5 decades. After the first description, and also thanks to the advances in the field of biomedical research, several additional genetic causes of (CVID) have been described. The current genetic landscape of (CVID) includes numerous genetic alterations that may cause or contribute to the development of (CVID), underscoring the complexity and heterogeneity of this disorder.

We have analysed data from 150 patients initially classified as having (CVID). About 10% had laboratory abnormalities suggesting known single gene disorders (eg: hyper-IgM syndrome), and in a few a genetic defect has been confirmed. We have attempted to sub-classify the remaining patients by analysis of their circulating lymphocytes. B lymphocyte markers have been used to estimate the numbers of circulating immature and class switched B cells; there is an association between the presence of high relative numbers of immature circulating B cells, splenomegaly and autoIMMUNE disease. About 25% of (CVID) patients have a moderate CD4+ T lymphopenia, sometimes with a relative expansion of CD8+ T cells. About 30% of (CVID) patients have persistent relatively high levels of circulating CD8+ T cells binding immunogenic peptides from EBV or CMV. Many of these patients also have high relative numbers of circulating CD8+ perforin positive T cells, and there is evidence that these cells may be responsible for neutropenia or inflammatory bowel disease in some patients. The clinical spectrum of (CVID) is diverse, with some patients suffering from few infections, and over 50% have evidence of structural lung damage. About 25% of UK patients have chronic inflammation in various organs, particularly the lungs, liver and spleen, often with granulomatous changes. Steroids are used to treat many of the patients with chronic inflammatory complications, although trials are in progress with anti-TNF agents. The incidence of these inflammatory complications is different between countries, being rare in Sweden. Attempts to correlate clinical phenotypes with the laboratory abnormalities described above have been disappointing, suggesting that unknown genetic factors unrelated to the cause of the immunoDEFICIENCY determine the complications; attempts to identify some of these factors will be discussed. Finally a provisional scheme to sub classify (CVID) patients according to lymphocyte abnormalities will be presented, the purpose being to focus the screening of candidate genes causing (CVID) to specific subsets of patients.

Background/objectives: The COMMON VARIABLE immunoDEFICIENCY ((CVID)) is known as the most prevalent symptomatic primary IMMUNE DEFICIENCY (PID) diseases, which is characterized by lower antibody serum levels as well as several infectious and noninfectious manifestations. In this regard, Bronchiectasis is considered as a COMMON respiratory complication and a vital challenge in (CVID) cases. This study aimed to evaluate the prevalence of bronchiectasis and investigate its association with other manifestations in (CVID) patients. Methods: A total of 297 patients diagnosed with (CVID) according to the relevant criteria were included in the current study. The query was performed to collect the participants’ demographic data, clinical manifestations, and laboratory findings. The analysis was performed between the two groups of the study including (CVID) patients with bronchiectasis and those without it. Results: Overall, the prevalence rate of bronchiectasis was calculated to be 28. 3%. Also, (CVID) patients with bronchiectasis had significant higher prevalence rates of respiratory manifestations, recurrent infections, otitis, clubbing, lymphoproliferative diseases, urinary tract infections, gastrointestinal diseases, dermatologic infections, allergy, and autoimmunity compared to the group including the patients without bronchiectasis. Notably, no significant differences were observed in antibodies serum levels between the patients with and without bronchiectasis. Moreover, CD19+ lymphocytes and CD8+ lymphocytes had significantly lower and higher percentages in (CVID) patients with bronchiectasis compared to those without it, respectively. Conclusion: The higher prevalence of bronchiectasis in (CVID) patients might be correlated with some other severe respiratory and off-respiratory clinical complications. Therefore, these manifestations should be precisely managed to impede a serious condition of bronchiectasis in (CVID) patients.