Local eosinophils are associated with increased IgA subclass levels in the sinonasal mucosa of chronic rhinosinusitis with polyp patients.

BACKGROUND: Chronic rhinosinusitis (CRS) describes an inflammatory condition affecting the sinonasal mucosa. As the immune system players such as immunoglobulins play prominent roles in the development of CRS, we aimed to investigate the expression of IgA subclasses and factors involved in IgA class switching in the sinonasal mucosa of CRS patients. METHODS: Specimens were collected from the sinonasal mucosa of the healthy controls and CRS patients. Histological assessments were performed by H&E and immunohistochemistry. Real-time PCR and ELISA methods were applied to measure gene expression and protein levels extracted from tissue samples, respectively. RESULTS: We observed that total IgA and subclass-positive cells were higher in the patient groups than controls. There was a significant correlation between the number of eosinophils and total IgA and subclasses-positive cells (Pv < 0.0001). The expression of CXCL13, BAFF, AID, and germline transcripts were increased in CRSwNP patients. In contrast to IgA2 levels, IgA1 levels were significantly increased in the sinonasal tissue of CRSwNP patients (Pv < 0.01). TGF-ß was significantly elevated in the sinonasal tissue of patients with CRSsNP. CONCLUSIONS: Increased protein levels of IgA subclasses and related antibody-producing cells were associated with elevated eosinophils in CRSwNP patients which may result in eosinophil pathological functions. Several therapeutic approaches might be developed to modulate the IgA production to ameliorate the inflammatory mechanisms in CRSwNP patients.

Levels of total IgA and IgA subclasses in the serum of chronic rhinosinusitis patients.

Background: Different inflammatory mechanisms take part in the immunopathogenesis of chronic rhinosinusitis (CRS). Immunoglobulin (Ig) A is the first-line defense in the airway tracts and other mucosal sites, but little is reported regarding its serum level in CRS patients. The purpose of current study is to determine the serum levels of total IgA, and its subclasses (IgA1, and IgA2) in CRS with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and control groups. Methods: In this case-control study the serum levels of total IgA and IgA subclasses were determined by Nephelometry and ELISA methods, respectively. The difference of the median concentrations was analyzed with the Kruskal-Wallis test. Collected data were analyzed using SPSS and presented by GraphPad Prism software. Results: A total of 10 CRSwNP patient, 10 CRSsNP patients and 10 healthy controls participated in our study. The mean age of the groups were 38.2±12.6, 25.6±10.54, and 30.1±9.5, respectively. The concentrations of total IgA were 156(120-165), 165 (149-173), and 172 (152.8-184.3) mg/dl, respectively. The concentrations of IgA1 were 107 (77.9-169.9), 156.1(112.8-175.6), and 130.4 (118.8- 175.2) mg/dl, respectively. The concentrations of IgA2 were 26.11 (18.41-38.11), 26.96 (15.48-38.39), and 23.2 (18.42-31.78) mg/dl, respectively. There was no significant difference in total IgA (p=0.120), IgA1 (p=0.397) and IgA2 (p=0.925) serum levels among three groups. Conclusion: Our study showed there is no difference in total IgA and IgA subclasses in the serum of CRS patients in comparison to healthy controls.

Determination of lymphocytes surface markers in patients with thermal burns and the influence of burn size on mononuclear cell subsets.

Background: Thermal burn injuries impair the host defence system. Hence, in the present study, we aimed at investigating the changes in the number and phenotype of peripheral blood lymphocyte populations (T, B, and natural killer cells) and their subpopulations in patients with thermal burns and determining the relationships with different sizes of total body surface area (TBSA). Methods: Blood samples from 67 patients, admitted to Motahary Burn Center in Tehran, with burns from 30% to more than 70% TBSA were collected on Days 3 and 7 postburn. Lymphocytes and their subpopulations were identified by monoclonal antibodies. The cells were analyzed using flow cytometry. The results were compared with healthy controls. Results: In this study, 3 and 7 days after burn injury, the percentages of CD3+, CD4+ and CD8+ lymphocyte significantly decreased, CD4+/CD8+ ratios were below the normal range, and CD19+ (B cells) significantly increased. No significant difference was obtained in the mean percentage of CD16+ (NK cells) between Days 3 and 7 postburn. Patients with burns of 30% TBSA or greater (>70%) had a significant reduction in CD3+, CD4+ and CD8+ ( T cells) numbers up to 7 days compared with 3 days after burn injury. Patients with 30% to >70 % TBSA burn failed to show any significant changes in CD4+/CD8+ ratio as well as CD16+ (NK cells) 3 to 7 days after burn. In patients with burns more than 30% to>70% TBSA, CD19+ (B cells) number changes were found to be complicated after 3 and 7 days. Conclusion: The results of this study suggest that alterations of immune cell surface markers and TBSA% can reflect postburn lymphocyte activation.

Osteogenic differentiation of stem cells derived from menstrual blood versus bone marrow in the presence of human platelet releasate.

In recent decades, stem cell therapy has been introduced as a novel therapeutic approach for patients suffering from bone disorders. Recently, menstrual blood has been identified as an easily accessible and recycled stem cell source. However, the osteogenic differentiation capacity of menstrual blood-derived stem cells (MenSCs) compared with other adult stem cells remained unsolved. The aim of this study was to investigate the osteogenic differentiation capacity of MenSCs compared to bone marrow-derived mesenchymal stem cells (BMSCs) in the presence of human platelet releasate (HPR). Our results showed that MenSCs were strongly positive for mesenchymal and negative for hematopoietic stem cell markers in a similar manner to BMSCs. In contrary to BMSCs, MenSCs exhibited marked expression of OCT-4 and a significantly higher proliferative capacity. Mineralization, as judged by alizarin red staining, was more pronounced in differentiated BMSCs than in differentiated MenSCs in an osteogenic medium fortified with fetal bovine serum (FBS). However, FBS substitution with HPR in a differentiation medium resulted in typical impact on intensity of MenSC mineralization. The results of semiquantitative reverse transcription-polymerase chain reaction showed comparable levels of parathyroid hormone receptor and osteocalcin transcripts in both types of differentiated stem cells in an HPR medium supplemented with osteogenic inducers. However, the upregulation level of alkaline phosphatase was relatively lower in differentiated MenSCs than that in differentiated BMSCs. We concluded that despite lower osteogenic differentiation capacity of MenSCs compared to BMSCs, substitution of FBS with HPR could equalize the osteogenic differentiation of MenSCs. Therefore, by taking advantage of osteogenic driving potential of HPR, MenSCs could be introduced as an apt and safe alternative to BMSCs for bone tissue-engineering purposes.

Association of KIR3DS1+HLA-B Bw4Ile80 combination with susceptibility to tuberculosis in Lur population of Iran.

BACKGROUND: Natural killer (NK) cells are the effector cells of innate immunity that respond to infection and tumor. Interactions between killer cell immunoglobulin like receptors (KIR) and human leukocyte antigen (HLA) class I molecules regulate NK cells responses to eliminate infected and transformed cells. OBJECTIVE: To investigate the impact of KIR genes, HLA ligand genes, and KIR-HLA combinations on susceptibility to tuberculosis (TB) in Lur population of Iran. METHODS: The genomic DNA of 50 patients with TB from Lorestan province of Iran was genotyped for sixteen KIR genes and their five major HLA class I ligands were determined by a polymerase chain reaction-sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy unrelated Iranian individuals. RESULTS: In Lur population of Iran, a significant decrease in frequency of KIR3DS1 was found in TB patients compared to control group (24% vs. 44.5%, OR=0.394, CI=0.194-0.798, p=0.013). Also, among the three activating genes that may use HLA class I molecules as their ligands, a significant decrease was shown in frequency of KIR3DS1 with HLA-B Bw4Ile80 ligand in TB patients compared to control group (4% vs. 23%, OR=0.14, CI=0.033-0.596, p=0.004). CONCLUSION: These findings imply a genetic imbalance between activating and inhibitory KIR genes and KIR-HLA combinations in Lur TB patients. Low level of activating KIR3DS1 and its combination with HLA-B Bw4Ile80 ligand might have an influence on the susceptibility to TB in Lur population of Iran.

KIR2DS3 is associated with protection against acute myeloid leukemia.

BACKGROUND: Interaction between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules is important for regulation of natural killer (NK) cell function. OBJECTIVE: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. METHODS: Cohorts of Iranian patients with acute myeloid leukemia (AML; n=40) and acute lymphoid leukemia (ALL; n=38) were genotyped for seventeen KIR genes and their three major HLA class I ligand groups (C1, C2, Bw4) by a combined polymerase chain reaction-sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy control individuals. RESULTS: We found a significantly decreased frequency of KIR2DS3 in AML patients compared to control group (12.5% vs. 38%, odds ratio=0.23, p=0.0018). Also, the KIR3DS1 was less common in AML group than controls (27.5% vs. 44.5%, p=0.0465, not significant after correction). Other analyses including KIR genotypes, distribution and balance of inhibitory and activating KIR+HLA combinations, and co-inheritance of activating KIR genes with inhibitory KIR+HLA pairs were not significantly different between leukemia patients and the control group. However, in AML patients a trend toward less activating and more inhibitory KIR-HLA state was observed. Interestingly, this situation was not found in ALL patients and inhibition enhancement through increase of HLA ligands and inhibitory combinations was the main feature in this group. CONCLUSION: Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity.