Selective immunoglobulin A deficiency in Iranian blood donors: prevalence, laboratory and clinical findings

Selective deficiency of immunoglobulin A (IgA) is the most frequent primary hypogammaglobulinemia. As some IgA-deficient patients have IgA antibodies in their plasma which may cause anaphylactic reactions, blood centers usually maintain a list of IgA-deficient blood donors to prepare compatible blood components. In this study we determined the incidence of selective IgA deficiency (SIgAD) in normal adult Iranian population. 13022 normal Iranian blood donors were included in this study. The assay which we used was adapted to the manual pipetting system and ELISA reader was used for screening. Other classes of immunoglobulins (G, M), as well as secretory IgA and IgG subclasses were tested in IgA deficient cases by ELISA. SPSS was used for statistical analysis.Among 13022 studied cases, 11608 blood donors were males (89.14%) and 1414 were females (10.86%). Their mean (+/-SD) age and weight were 38.5+/-11 years and 82+/-12 Kg respectively. Twenty of the screened samples were found by means of ELISA to be IgA-deficient (less than 5mg/dl), (frequency; 1:651). The data could indicate a compensation for IgA deficiency by serum IgM in one of our IgA deficient cases (Patient 5). We observed a correlation between IgG3 and serum IgA in deficient cases (r=0.498, P=0.025). Our results indicate that in present study the prevalence of S IgA D is in agreement with data from other Caucasians populations (from 1:300 to 1:700). In conclusion, Selective IgA Deficiency could be almost asymptomatic in most cases in general population. Our study suggests that; due to high frequency of IgA deficiency in Iran, it seems necessary to measure IgA levels for every blood donor and blood recipient to find IgA deficient cases.     

Ankylosing spondylitis monocyte-derived macrophages express increased level of A<Subscript>2A</Subscript> adenosine receptor and decreased level of ectonucleoside triphosphate diphosphohydrolase-1 (CD39), A<Subscript>1</Subscript> and A<Subscript>2B</Subscript> adenosine receptors

Macrophages play an important role in the ankylosing spondylitis (AS) auto-inflammatory responses and fibrocartilage destruction. Adenosine is a key modulator of inflammatory conditions. The various effects of adenosine are mediated by its interaction with adenosine receptors (AR). In this study, we investigated the mRNA expression of A₁, A_2A, A_2B, and A₃ adenosine receptors, ectonucleoside triphosphate diphosphohydrolase-1 (CD39), and ecto-5′-nucleotidase (CD73) in the monocyte-derived macrophages from AS patients in comparison to healthy controls. We also explored the correlation between analyzed gene expression and patients’ clinical manifestations. Whole blood-separated monocytes from 23 healthy controls and 23 active AS patients were stimulated by macrophage colony-stimulating factor (M-CSF) for 7 days and differentiated to macrophages. Monocyte and macrophage markers were analyzed by flow cytometry. Analysis of adenosine receptors (ADORA1? ADORA2A? ADORA2B? ADORA3), CD39 and CD73 gene expression was performed by SYBR green real-time PCR. Our results demonstrated monocyte-derived macrophages from AS patients expressed increased level of A_2AAR and reduced level of A₁, A_2BAR, and CD39 mRNA compared to healthy controls. We found an inverse correlation between A_2AAR mRNA expression and Bath Ankylosing Spondylitis Functional Index (BASFI) score in AS patients. According to our results, altered expression level of adenosine-relying system would be involved in AS macrophage dysfunction and inflammation and correlated with functional status in AS patients.     

Physiologic role of decidual beta1 integrin and focal adhesion kinase in embryonic implantation

Implantation refers to a series of interactions between embryo and endometrium including hatching, attachment, and outgrowth. We investigated the expression and function of beta1 integrin and focal adhesion kinase (FAK) in human decidual cells during implantation. Immunofluorescent staining localized beta1 integrin to surfaces of cultured decidual cells. Double staining for beta1 integrin and mediators of intracellular signaling involving beta1 integrin, such as FAK and vinculin, colocalized beta1 integrin with these substances, suggesting that human decidual cells express beta1 integrin in the focal adhesion region. We next investigated the actions of beta1 integrin and FAK in implantation by co-culturing mouse embryos and human decidual cells. Mouse blastocysts attached to cultured decidual cells after embryo hatching, usually within 24 h of culture initiation. Blastocysts attached to decidual cells exhibited extensive outgrowth at 48 h. Treatment of decidual cells with an antibody against beta1 integrin or with an antisense FAK oligonucleotide did not affect hatching or attachment of blastocysts, but either one could inhibit outgrowth. Thus, it was concluded that human decidual beta1 integrin and FAK participate in this final step of implantation.     

Effect of physical training on the proportion of slow‐twitch type I muscle fibers,a novel nonimmune‐mediated mechanism for muscle impairment in polymyositis or dermatomyositis

Objective

To compare muscle fiber type composition and muscle fiber area in patients with chronic polymyositis or dermatomyositis and healthy controls, and to determine whether physical training for 12 weeks could alter these muscle characteristics.

Methods

Muscle fiber type composition and muscle fiber area were investigated by biochemical and immunohistochemistry techniques in repeated muscle biopsy samples obtained from 9 patients with chronic myositis before and after a 12‐week exercise program and in healthy controls. Muscle performance was evaluated by the Functional Index (FI) in myositis and by the Short Form 36 (SF‐36) quality of life instrument.

Results

Before exercise, the proportion of type I fibers was lower (mean ± SD 32% ± 10%) and the proportion of type IIC fibers was higher (3% ± 3%) in patients compared with healthy controls. After exercise, percentage of type I fiber increased to 42% ± 13% (P < 0.05), and type IIC decreased to 1% ± 1%. An exercise‐induced 20% increase of the mean fiber area was also observed. The functional capacity measured by the FI in myositis and the physical functioning subscale of the SF‐36 increased significantly. Improved physical functioning was positively correlated with the proportion of type I fibers (r = 0.88, P < 0.01) and type II muscle fiber area (r = 0.70, P < 0.05).

Conclusion

Low muscle endurance in chronic polymyositis or dermatomyositis may be related to a low proportion of oxidative, slow‐twitch type I fibers. Change in fiber type composition and increased muscle fiber area may contribute to improved muscle endurance and decreased muscle fatigue after a moderate physical training program.     

Matched related donor hematopoietic stem cell transplantation results in a long‐term follow‐up of a pediatric acquired severe aplastic anemia subset: A stem cell source perspective

HSCT has substantially improved pediatric acquired SAA patients' outcomes. Retrospectively, we attempted to assess the outcome of MRD HSCT in 65 pediatric patients referred to a single center from 1992 to 2012. We were particularly interested to find out whether source of SC (PB, n = 40 and BM, n = 25) significantly impacts EFS and GVHD incidence. With a median follow‐up of 45 months, total EFS was 87.7%; EFS for PB and BM groups was 87.5% and 88%, respectively. Acute GVHD (grades 3–4) occurred in 13 patients (PB, n = 10 [25%] and BM, n = 3 [12%]), acute GVHD (grades 2–4) occurred in 24 (PB, n = 16 [40%] and BM, n = 8 [32%]). Extensive chronic GVHD occurred in five patients (PB, n = 3 [7.5%] and BM, n = 2 [8%]). Cox regression revealed that elapsed time of <10 months between diagnosis and HSCT is associated with improved survival (hazard ratio, 95% CI = 1.204, 1.010–1.434, p = 0.038). SC source did not significantly affect EFS, incidence of acute GVHD (grades 3–4), or extensive chronic GVHD (p = 0.938, 0.121, and 0.487, respectively). Based on our findings, pediatric acquired SAA patients are benefitted most if MRD‐HSCT is carried out early in disease process and SC source does not affect outcome of MRD‐HSCT in these patients.     

Anxiety and depression in rheumatoid arthritis: an epidemiologic survey and investigation of clinical correlates in Iranian population

Psychiatric disorders occur in a considerable proportion of patients with rheumatoid arthritis (RA). This study was conducted in order to evaluate the prevalence of anxiety and depression in Iranian RA patients. In the cross sectional study, 414 RA patients were enrolled prospectively during a period of 6 months from RA clinic of Rheumatology Research Center. Beck’s and Cattell’s inventories were applied to investigate depression and anxiety in RA patients. RA activity was measured by Disease Activity Score and patients’ disability was assessed by Health Assessment Questionnaire. Levels of pain perception were stratified based on Visual Analog Scale. The prevalence of depression was 63.6 % and anxiety was in 84.1 % among RA patients. Mixed anxiety and depression was detected in 60.2 % of the study population. Functional disability was significantly associated with severity of depressive and anxiety symptoms (p < 0.001); however there was no association between disease activity and depression or anxiety (p = 0.420). There was weak correlation between disease activity score and functional disability (Spearman’s rho = 0.33; p < 0.01). Severe levels of depression and anxiety were associated with higher levels of pain perception (p < 0.001). Our study stressed the impact of depressive and anxiety symptoms in functional disability and pain perception of RA patients. Our results point out the multidisciplinary management of RA.     

Thrombolytic Therapy for Right-Sided Mechanical Pulmonic and Tricuspid Valves: The Largest Survival Analysis to Date

Data regarding thrombolytic treatment of right-sided mechanical valve thrombosis are almost nonexistent, and all current guidelines arise from very small case series. We retrospectively studied the in-hospital and long-term outcome data of a larger series of patients who had received, from September 2005 through June 2012, thrombolytic therapy for right-sided mechanical pulmonary valve or tricuspid valve thrombosis.We identified 16 patients aged 8–67 years who had undergone thrombolytic therapy for definite thrombotic mechanical valve obstruction in the tricuspid or pulmonary valve position (8 in each position). All study patients except one had subtherapeutic international normalized ratios. The 8 patients with pulmonary mechanical valve thrombosis had a 100% response rate to thrombolytic therapy, and their in-hospital survival rate was also 100%. The 8 patients with tricuspid mechanical valve thrombosis had a 75% response rate to thrombolytic therapy, with an in-hospital survival rate of 87.5%. The one-year survival rate for mechanical valve thrombosis treated with thrombolytic therapy (whether pulmonary or tricuspid) was 87.5%.On the basis of our data, we recommend that thrombolytic therapy remain the first-line therapy for right-sided mechanical valve thrombosis in adults or children—including children with complex congenital heart disease and patients with mechanical pulmonary valve thrombosis. Surgery should be reserved for patients in whom this treatment fails.