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Breast cancer (BC) is the leading cause of cancer deaths in women. One of the reasons for the failure of BC treatment is reportedly the ineffectiveness of chemotherapeutic drugs against breast cancer stem-like cells (BCSCs). HER2 receptors have an important role in the self-renewal of BCSCs. Matrix metalloproteinase (MMP) and cytokine levels were found to be higher in BCSCs, which demonstrates their potential metastatic capacity. Therefore, the aim of this study was to evaluate the response of BCSCs to trastuzumab and to investigate the MMP levels in primary breast cancer cells and HER2+ BCSCs. Tumour tissue samples were obtained during surgical intervention from ten breast cancer patients, and primary culture cells were established from these tissues. Four major molecular subgroups were sorted from the primary culture: HER2+ BCSCs (CD44+CD24−HER2+), HER2− BCSCs (CD44+CD24−HER2−), HER2− primary culture cells (CD44+CD24+HER2−) and triple positive primary culture cells (CD44+CD24+HER2+). These cells were cultured and treated with trastuzumab, paclitaxel, carboplatin, and the combination of those three drugs for 96 h. Cellular responses to these drugs were determined by XTT cytotoxicity test. MMPs and cytokine array analysis showed that MMPs and TIMP-1, TIMP-2 proteins were expressed more in HER2+ BCSCs than in primary culture. HER2− BCSCs were more resistant to drugs than HER2+ BCSCs. Our findings suggest that the presence of HER2− BCSCs may be responsible for primary trastuzumab resistance in HER2+ BC cell population. Further studies investigating the function of MMPs are needed for drug targeting of BCSCs. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic granulomatous mastitis (IGM) is a rare, chronic inflammatory benign breast disease. Although the etiology of this disease is unknown, it has been suggested that hormonal disorders, autoimmunity, smoking, and α1-antitrypsin deficiency may play a role in the etiopathogenesis. The aim is to investigate the changes in cytokine profiles including interleukin (IL)-4, -8, -10, -17, and tumor necrosis factor (TNF)-alpha in patients with IGM. Methods: Forty-seven patients with pathologically diagnosed IGM and 30 healthy women were included. The cytokines including IL-4, -8, 10, -17, and TNF-alpha were measured by human enzyme-linked immunosorbent assay. Results: The IL-8, IL-10, and IL-17 levels were higher in IGM patients than control group (p =.002; p =.008; and p =.018, respectively). The IL-8 levels of patients with active lesions and in remission were statistically higher than the control group (p =.027 and p =.015, respectively). IL-10 levels of patients in remission were higher than the control group (p =.024). There was no difference in IL-4 and TNF-ɑ levels between all groups. Conclusion: These results showed that proinflammatory cytokines including IL-8 and IL-17 have role in pathogenesis of IGM. However, the increased levels of IL-10 in especially patients in remission suggest that it reduces the release of proinflamatory cytokines as well as suppressing their function and activation for controlling IGM. Although IGM is thought to be a surgical disease, these cytokine changes indicate the presence of serious immune dysregulation. This suggests that in the treatment of IGM, treatment needs to evolve from surgery to medical treatment. Key points • The IL-8, IL-10, and IL-17 levels were higher in IGM patients than in control group. • The IL-8 levels of both patients with active lesions and in remission were high. • There was no difference in IL-4 and TNF-ɑ levels between all groups. [ABSTRACT FROM AUTHOR]

Children with Down syndrome (DS) have a high incidence of recurrent respiratory tract infections, leukaemia and autoimmune disorders, suggesting immune dysfunction. The present study evaluated the role of the CD19 complex and memory B cells in the pathogenesis of immunodeficiency in children with DS. The expression levels (median fluorescein intensity—MFI) of CD19, CD21 and CD81 molecules on the surface of B cells and memory B cell subsets were studied in 37 patients and 39 healthy controls. Twenty-nine of the DS group had congenital cardiac disease. The B cell count was significantly low in children with DS compared with healthy age-matched controls for all three age groups (under 2 years; 2–6 years and older than 6 years). The MFI of CD19 was reduced in all the age groups, whereas that of CD21 was increased in those older than 2 years with DS. The expression level of CD81 was significantly increased in those older than 6 years. Age-related changes were also detected in memory B cell subsets. The frequency of CD27+IgD+IgM+ natural effector B cells was reduced in children with DS who had needed hospitalisation admission due to infections. The observed intrinsic defects in B cells may be responsible for the increased susceptibility of children with DS to severe respiratory tract infections. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the role of the CD19 complex in the pathogenesis of transient hypogammaglobulinemia of infancy (THI) and to better characterize the subsets of memory B cells. The study population consisted of 22 male and 14 female patients with a mean age at presentation of 20 ± 9.9 months. The CD19 complex and B cell subsets were evaluated by flow cytometry. While the CD19 median fluorescence index (MFI) in patients with THI was significantly lower than controls (122.9 ± 66.7 in patients; 184.2 ± 39 in controls, p < 0.01), expression of CD21 and CD81 was increased (94.4 ± 3, 96.8 ± 2.5 % in patients; 91 ± 3.9; 94.7 ± 3.5 % in controls, p < 0.01 vs. p < 0.05, respectively). The expressions of switched memory B cells and IgM memory B cells were found to be reduced in THI. Considering that the CD19 complex regulates the events following antigen stimulation, the change in CD19 complex detected in THI may be related to insufficiency of antibody production. [ABSTRACT FROM AUTHOR]

Focal epithelial hyperplasia, also known as Heck's disease, is a rare but distinctive entity of viral etiology with characteristic clinical and histopathological features. It is a benign, asymptomatic disease of the oral mucosa caused by human papilloma viruses (HPV). Previous studies postulated an association between these lesions and immunodeficiency. Genetic deficiency of adenosine deaminase (ADA) results in varying degrees of immunodeficiency, including neonatal onset severe combined immunodeficiency (ADA-SCID), and milder, later onset immunodeficiency. We report a 12-year-old girl with the late onset-ADA deficiency presenting with Heck's disease. Our case report should draw attention to the possibility of immunodeficiency in patients with HPV-induced focal epithelial hyperplasia. [ABSTRACT FROM AUTHOR]

Although the presence of physiologic anti-CD95 (Fas, APO-1) autoantibodies in intravenous immunoglobulin (IVIG) preparations is known, the effects of these antibodies in patients with common variable immunodeficiency are unclear (CVID). The aim of the study was to assess the effects of IVIG in Fas expression, activation markers and the subsets of T cells in patients with CVID. We studied 15 cases with CVID and 10 healthy controls with no signs of immunodeficiency. The Fas expression of T cells, activation markers (CD25, CD69 and HLA-DR) and T-cell subsets were analyzed by four-color flow cytometry. We found that the Fas expression of CD3+ T cells in patients was significantly higher than in controls. In addition, there was a significant increase in the Fas expression of CD3+ T cells and CD4+ T cells, and the CD25 expression of CD3+ and CD4+ T cells after IVIG supplementation ( P < 0.05). The CD69 and HLA-DR expressions of T cells and CD8+ T cells were not affected by IVIG infusion. Our observation showed that IVIG replacement causes an increase in the Fas and CD25 expressions in patients with CVID. These data suggest that the Fas protein may have an important role in the effects of IVIG for the control of autoimmunity in patients with CVID, as well as in the generation of autoimmune disease. [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency (CVID) is a disorder characterized by hypogammaglobulinemia, poor antibody responses and recurrent bacterial infections. CVID patients have a higher prevalence of autoimmune disease and some of them develop noncaseating granulomas of the lungs, spleen, liver, skin, lymph nodes and eye. We report herein a 5-year-old girl with CVID presented with cutaneous nodules, granulomatous uveitis and oligoarthritis. The lesions, arthritis and uveitis responded well to treatment with the systemic administration of steroid. Different autoimmune diseases could be seen together in children with CVID. These patients require therapeutic cooperation of the immunologists with different specialists, including dermatologists, rheumatologists and ophthalmologists. [ABSTRACT FROM AUTHOR]

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency. [ABSTRACT FROM AUTHOR]

Juvenile rheumatoid arthritis (JRA) is a complex disease involving the interactions of several cell populations with different mediators. Herein, we report a five-year-old girl with systemic-onset JRA. At admission, peripheral blood flowcytometric analysis showed the percentages of CD19+ and CD20+ B cells were <1%. These values returned to normal on the tenth day of steroid treatment. This is the first report of JRA presented with absence of B lymphocytes in the literature and suggested that lymphocytes subset analysis could change with treatment in patients with JRA. Different clinical signs and symptoms reflecting aspects of JRA are critical for the etiology of the disease and to identify new strategies for treatment. [ABSTRACT FROM AUTHOR]

Chilaiditi syndrome is the interposition of the colon between the diaphragma and the liver. In general, patients are asymptomatic, but some patients have been associated with gastrointestinal and respiratory symptoms. A 5-month-old infant boy was admitted to the hospital with a history of cough, cyanosis and recurrent respiratory distress that had persisted during the preceding 2 months. The chest X-ray revealed an elevation of the right hemidiaphragma caused by the presence of a dilated colonic loop below. Computed tomography showed a hepatodiaphragmatic interposition of the colon, leading to the diagnosis of Chilaiditi syndrome. The patient was conservatively treated with oxygen, fluid supplementation and stool softeners. We conclude that this rare syndrome should be kept in mind when young patients present with recurrent respiratory distress. [ABSTRACT FROM AUTHOR]

Although congenital defects of diaphragma often occur in the period immediately following birth, 10-20% of these cases are diagnosed later. We report on a 7-month-old male infant with late-presenting congenital diaphragmatic hernia associated with a thoracic ectopic kidney. We conclude that congenital diaphragmatic defects should be considered in young children with respiratory distress and that computerized tomography is a noninvasive and accurate diagnostic method in the evaluation of additional abnormalities in these patients. [ABSTRACT FROM AUTHOR]