Association between vitamin d deficiencies in sarcoidosis with disease activity, course of disease and stages of lung involvements

Background: Despite negative association between 25-hydroxy vitamin D and incidence of many chronic respiratory diseases, this feature was not well studied in sarcoidosis. Current study investigated the association between 25-hydroxy vitamin D deficiency with sarcoidosis chronicity, disease activity, extra-pulmonary skin manifestations, urine calcium level and pulmonary function status in Iranian sarcoidosis patients. Results of this study along with future studies, will supply more effective programs for sarcoidosis treatment. Methods: Eighty sarcoidosis patients in two groups of insufficient serum level and sufficient serum level of 25-hydroxy vitamin D were studied. Course of sarcoidosis was defined as acute and chronic sarcoidosis. Pulmonary function test (PFT) was assessed by spirometry. Skin involvements were defined as biopsy proven skin sarcoidosis. 24-hour urine calcium level was used to specify the disease activity. Stages of lung involvements were obtained by CT-scan and chest X-ray. The statistical analyses were evaluated using Statistical Package for the Social Sciences. Results: A significant negative correlation was obtained between vitamin D deficiency in sarcoidosis patients and disease chronic course and stages two to four of lung involvements. Considering other parameters of the disease and vitamin D deficiency, no significant correlation was detected. Conclusions: In conclusion, results of the current study implies in the role of vitamin 25(OH)D deficiencies in predicting the course of chronic sarcoidosis. Furthermore, it was concluded that vitamin 25(OH)D deficiency can direct pulmonary sarcoidosis toward stage 2–4 of lung involvements

What Immunological Defects Predispose to Non-tuberculosis Mycobacterial Infections?

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil.  NTM cause a variety of diseases in humans that mainly affect the lung. A predisposition to pulmonary NTM is evident in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases and other chronic diseases with pulmonary manifestations. Lung infections are not the only consequences of being infected by NTM as they can also infect skin and soft tissue and may also cause lymphadenitis (predominantly in young children) and disseminated disease in human immunodeficiency virus (HIV)-infected patients or those with severely compromised immune system. NTM are also found in many subjects without any known risk factors.  Although the recent advances in imaging and microbiologic techniques including gene sequencing have provided a better view of the problems caused by NTM and has enhanced our understanding of the disease, many uncertainties regarding the immunologic response to NTM still exist. There is also limited data on the immunogenetics of NTM infection. Here, the authors reviewed the main immunogenetic defects as well as other immunological conditions which are associated with an increased the risk of NTM infections

Effect of mesenchymal stem cell-derived exosomes on the induction of mouse tolerogenic dendritic cells

Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T‐cell activation via direct cell–cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T‐cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC‐derived exosomes on the induction of mouse tolDCs, murine adipose‐derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick‐TC kits. BM‐derived DCs (BMDCs) were prepared and cocultured with MSCs‐derived exosomes (100 μg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1μg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester‐labeled BALB/C‐derived splenocytes p. Interleukin‐6 (IL‐6), IL‐10, and transforming growth factor‐β (TGF‐β) release were measured by enzyme‐linked immunosorbent assay. MSC‐derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells ( ≤ .05). MSC‐derived exosomes decrease IL‐6 release but augment IL‐10 and TGF‐β release (p ≤ .05). Lymphocyte proliferation was decreased (p ≤ .05) in the presence of DCs treated with MSC‐derived exosomes. CMSC‐derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC‐induced immune responses

Male reproductive health under threat: Short term exposure to radiofrequency radiations emitted by common mobile jammers

Background: Modern life prompted man to increasingly generate, transmit and use electricity that leads to exposure to different levels of electromagnetic fields (EMFs). Substantial evidence indicates that exposure to common sources of EMF such as mobile phones, laptops or wireless internet-connected laptops decreases human semen quality. In some countries, mobile jammers are occasionally used in offices, shrines, conference rooms and cinemas to block the signal. Aims: To the best of our knowledge, this is the first study to investigate the effect of short term exposure of human sperm samples to radiofrequency (RF) radiations emitted by common mobile jammers. Subjects and Methods: Fresh semen samples were collected by masturbation from 30 healthy donors who had referred to Infertility Treatment Center at the Mother and Child Hospital with their wives. Female problem was diagnosed as the reason for infertility in these couples. Statistical Analysis: T-test and analysis of variance were used to show statistical significance. Results: The motility of sperm samples exposed to jammer RF radiation for 2 or 4 h were significantly lower than those of sham-exposed samples. These findings lead us to the conclusion that mobile jammers may significantly decrease sperm motility and the couples′ chances of conception. Conclusion: Based on these results, it can be suggested that in countries that have not banned mobile jammer use, legislations should be urgently passed to restrict the use of these signal blocking devices in public or private places

The role of pattern recognition receptors in lung sarcoidosis

Sarcoidosis is a granulomatous disorder of unknown etiology. Infection, genetic factors, autoimmunity and an aberrant innate immune system have been explored as potential causes of sarcoidosis. The etiology of sarcoidosis remains unknown, and it is thought that it might be caused by an infectious agent in a genetically predisposed, susceptible host. Inflammation results from recognition of evolutionarily conserved structures of pathogens (Pathogen-associated molecular patterns, PAMPs) and/or from reaction to tissue damage associated patterns (DAMPs) through recognition by a limited number of germ line-encoded pattern recognition receptors (PRRs). Due to the similar clinical and histopathological picture of sarcoidosis and tuberculosis, Mycobacterium tuberculosis antigens such early secreted antigen (ESAT-6), heat shock proteins (Mtb-HSP), catalase-peroxidase (katG) enzyme and superoxide dismutase A peptide (sodA) have been often considered as factors in the etiopathogenesis of sarcoidosis. Potential non-TB-associated PAMPs include lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria, peptidoglycan, lipoteichoic acid, bacterial DNA, viral DNA/RNA, chitin, flagellin, leucine-rich repeats (LRR), mannans in the yeast cell wall, and microbial HSPs. Furthermore, exogenous non-organic antigens such as metals, silica, pigments with/without aluminum in tattoos, pesticides, and pollen have been evoked as potential causes of sarcoidosis. Exposure of the airways to diverse infectious and non-infectious agents may be important in the pathogenesis of sarcoidosis. The current review provides and update on the role of PPRs and DAMPs in the pathogenesis of sarcoidsis

CD4:CD8 ratio: A valuable diagnostic parameter for pulmonary sarcoidosis

Sarcoidosis is a multi-organ disease and is characterized by sarcoidal noncaseating granuloma comprised of T-helper/inducer (CD4+) lymphocytes and scant cytotoxic (CD8+) T-lymphocytes. CD4+:CD8+ T-cell elevated ratio is a characteristic diagnostic parameter for sarcoidosis. This is the first report from Iran evaluating the CD4:CD8 ratio capability in differentiating pulmonary sarcoidosis from other interstitial lung diseases (ILDs) on a large cohort. Fifty pulmonary sarcoidosis patients and 50 non-sarcoidosis interstitial lung diseases (nsILDs) patients were included in the current study. Bronchoalveolar lavage (BAL) was performed using flexible fiberoptic bronchoscopy and flow cytometer. Non-sarcoidosis group was established by 50 components that were classified into eight subgroups. Fifty-two percent of sarcoidosis patients and 62% of non-sarcoidosis interstitial lung disease patients had normal spirometric results. The CD4/CD8 ratio was significantly higher in sarcoidosis than in non-sarcoidosis interstitial lung diseases (p 3.5 in 33.3%, 2.5-3.5 in 7.1%, 1.5-2.5 in 20.2% and < 1.5 in 39.4% of the entire study population. The best cut off point was 1.1 with the sensitivity of 92% and specificity of 80% for distinguishing sarcoidosis from other interstitial lung diseases. Performing bronchoalveolar lavage as the safe and rapid first step confirms the diagnosis of sarcoidosis in 92% of cases (current study sensitivity). Hence, performing an invasive procedure was required in a few patients only. Bronchoalveolar lavage flow cytometry in the assessment of clinical and radiological findings supplies an appropriate diagnostic adjunct for discriminating sarcoidosis from non-sarcoidosis interstitial lung diseases

What immunological defects predispose to the non-tuberculosis mycobacterial infections?

Nontuberculous mycobacteria (NTM) are categorized as one of the large and diverse groups of environmental organisms which are abundant in water and soil. NTM cause a variety of diseases in human in which mainly lung is involved. A predisposition to pulmonary NTM is seen in patients with parenchymal structural diseases including bronchiectasis, emphysema, tuberculosis (TB), cystic fibrosis (CF), rheumatologic lung diseases, and other chronic diseases with pulmonary manifestations. Lung infections are not the only consequences of being infected by NTM as it can also infect skin and soft tissue and may also cause lymphadenitis (predominantly in young children) and disseminated disease in HIV-infected patients or those with severely compromised immune system. NTM is also reported in many subjects without any known risk factor. Although the recent advances in imaging and microbiologic techniques including gene sequencing has provided a better view of the problems caused by NTM and has enhanced our understanding of the disease, many uncertainties regarding the immunologic response to NTM still exist. There is also limited data on the immunogenetics of NTM infection. Here, the authors reviewed the main immunogenetic defects as well as other immunological conditions which are associated with an increased the risk of NTM infections