Inflammation is an important component of numerous cancers and chronic diseases and many inflammatory mediators have been shown to have potential prognostic roles. Tumor-infiltrating mast cells can promote tumor growth and angiogenesis, but the mechanism of mast cell activation is unclear. Early studies have shown that immunoglobulin free light chains (FLC) can trigger mast cell activation in an antigen-specific manner. Increased expression of FLC is observed within the stroma of many human cancers including those of breast, colon, lung, pancreas, kidney, and skin. These overexpressed FLCs are co-localized to areas of mast cell infiltration. Importantly, FLC expression is associated with basal-like cancers with an aggressive phenotype. Moreover, FLC is expressed in areas of inflammatory cell infiltration and its expression is significantly associated with poor clinical outcome. In addition, serum and bronchoalveolar fluid FLC concentrations are increased in patients with idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP) compared to control subjects. In this review, we provide an update on the role of FLC in the pathogenesis of several lung disorders and indicate how this may contribute to new therapeutic opportunities. 

Current therapeutic approaches in allergic diseases especially asthma generally focus on using immunological strategies. According to the importance of FceRI in controlling allergic response we used two extracellular regions of Fc epsilon receptor I (FceRI) beta subunit peptides to design two peptide-based vaccines. Probably these peptides vaccines by triggering the immune response to FceRI can reduce the allergic symptoms through blocking the IgE specific receptor. Two extracellular parts of FceRI beta subunit were made by peptide synthesizer and conjugated with keyhole limpet Hemocyanin. These conjugated peptides were used and evaluated as therapeutic vaccines in allergic airway inflammation mouse model. Total IgE and anti ovalbumin specific IgE were measured in mice serum and compared in vaccinated and unvaccinated allergic mice. Histamine, prostaglandin D2 (PGD2), IL-4 and IL-13 were measured in bronchoalveolar lavage (BAL) fluid of vaccinated allergic mice versus unvaccinated and histopathologic examination were performed in studied groups. After vaccination of mice with each of the peptide vaccines the specific antibodies titer increased significantly in vaccinated groups versus unvaccinated. In histopathologic study, lavage eosinophil percentage and peribronchial inflammation in lung sections of vaccinated groups was decreased (p<0.05). Also the allergic components including total IgE, anti ovalbumin specific IgE, histamine, PGD2, IL-4, and IL-13 showed substantial decline in vaccinated allergic mice.  Thus targeting the extracellular regions of FceRI beta subunit by peptide-based vaccines and induction of specific antibodies against them can reduce allergic responses in allergic mice model.  

Aeroallergens play an important role in developing allergic diseases. The aim of this study was to determine the outdoor and indoor sensitization using a specific regional panel of aeroallergens in allergic patients. All patients with allergic symptoms referred to Immunology, Asthma and Allergy Research Institute (IAARI) in Tehran, Iran from December 2010 to July 2013 entered this cross sectional study. We evaluated serum samples for specific IgE against 20 selected aeroallergens provided by a specific panel (RIDA Allergy Screen test, IAARI panel). A p value less than 0.05 was considered as significant. The patients (n=602) were 49.8 % male and 50.2% female. The median age was 9 years. Positive specific IgE at least to one allergen was 53.2%. The percentages of patients with only outdoor or indoor sensitization were 37.5 and 19.7%, respectively. Moreover, 42.8% showed sensitization to both indoor and outdoor aeroallergens. The most common outdoor aeroallergens in decreasing order were plane tree (32.8%), Bermuda grass (32.2%), timothy grass (30.6%), saltwort (28.4%). The percentage of specific IgE to indoor allergens including mold and mite were 23.8 % and 22.2%, respectively. There was a statistically significant relationship between specific IgE to timothy grass and mold allergens between two genders (p=0.04 and p=0.02, respectively).The results of this study shows that outdoor aeroallergens can be considered as the most common causes of allergic symptoms in our allergic patients.

Farmers are usually exposed to various inhaled allergens like pollens, mites, molds, and animal dander in their working environment which may lead to allergic rhinitis, asthma and urticaria. The purpose of this study was to identify sensitization to various aeroallergens in farmers and their occupational allergy symptoms. This cross sectional study included 103 male farmers and 100 non-farmer healthy controls. The work-related symptoms of farmers were recorded with a questionnaire. Spirometry and skin prick tests with 15 commercial allergen extracts were performed in both farmers and controls. The rate of sensitization to at least one of the applied aeroallergens was 47.6% in farmers compared to 65% in the control group (OR=0.48; CI 95%, 1.08 to 2.07) according to skin prick tests, after adjusting for age. Occupational allergy symptoms were reported by 54.3% farmers. Mean FEV₁/FVC was significantly lower in farmers than in controls (p<0.001). The results of this study showed that farmers had no increased risk of sensitization to aeroallergens. Sensitization to pollens was more prevalent than to mites among the farmers in our study and smoking was an important predisposing factor in farmers who suffered from occupational allergy symptoms.

In Pakistan about 3.7% of the population is suffering from asthma, a chronic inflammatory disorder of airways. Asthma has wide spectrum of predisposing factors including environment and genetics. Many studies have been performed to determine association of asthma with serum IgE and major histocompatibility complex (MHC) alleles but conflicting results were reported. Therefore, present study was designed to determine frequency of HLA-DQβ1*0201 and DQβ1*0301 alleles in patients with bronchial asthma. This case control study included 85 asthmatic patients and 85 healthy controls. HLA-DQβ1*0201 and DQβ1*0301 alleles were detected by allele specific PCR and serum IgE was determined by ELISA. Median and inter-quartile range (IQR) of total IgE level were more increased in asthma patients (585.7 IU/mL and 247.2-848.1 IU/mL) compared to healthy controls (65.1 IU/mL and 28.1-181.3 IU/mL) (p<0.001). Frequency of HLA-DQβ1*0201 and -DQβ1*0301 alleles was more in healthy controls (32% and 38%, p=0.616) as compared to bronchial asthma patients (28% and 26%, p= 0.09). There was a significant association of IgE levels and HLA-DQβ1*0201 allele. Patients positive for HLA-DQβ1*0201 allele had low level of serum IgE 357.2 IU/mL (153.9-634.3 IU/mL) compared to the patients negative for this HLA allele i.e. 642.9 IU/mL (289.8-1299.5IU/mL) (p=0.005), whereas, HLA-DQβ1*0301 allele was not associated with total serum IgE level (p=0.865). Our findings show that HLA-DQβ1*0201 and -DQβ1*0301 alleles were not associated with asthma; however, HLA-DQβ1*0201 allele was associated with low levels of total serum IgE in the study population.

T-cell immunoglobulin and mucin domain (TIM)-3 have been shown to negatively regulate Th1 cell-mediated immunity. Activation of TIM-3 by galectin-9 induces Th1 cell apoptosis, which may contribute to skewing of immune response towards Th2-dominant immunity. The aim of this study was to determine whether certain genetic variations of TIM-3 influence predisposition to asthma in a sample of Iranian population. This case-control study was conducted on 209 patients with asthma and 200 healthy controls. The +4259 T>G and -574 G>T polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and amplification refractory mutation system-PCR(ARMS-PCR). Total serum IgE was further measured with ELISA. Notably, +4259T > G and-574G>T polymorphisms of TIM-3 were significantly associated with the susceptibility to asthma. In addition, the present study showed a significant difference between the distribution frequency of the GT + TT genotype and T allele on the +4259 T>G and -574 G>T locus between the groups.However, no correlation between the +4259 T > G and -574G > T polymorphisms and total serum IgE levels were observed. Together these results suggest that the TIM-3 +4259 T>G and -574 G>T polymorphisms are greatly associated with the susceptibility of Iranian population to asthma, which could open up new horizons for  better understanding of the pathophysiology, diagnostic, prognostic and therapeutic approaches of asthma. 

IL-33 and IL-37 (new cytokines of IL-1 family), soluble form of vascular endothelial growth factor receptor-2 (sVEGFR2) as well as membranous expression of VEGFR2 have some key roles in the pathogenesis of autoimmune and inflammatory diseases. The aim of this study was to correlate circulatory changes of these factors with the severity of multiple sclerosis (MS) as an autoimmune and inflammatory disease. Our case-control study was performed on 84 patients with MS and 75 healthy subjects. The serum levels of IL-33, IL-37 and sVEGFR2 in the peripheral blood samples of all participants were measured by enzyme-linked immune sorbent assay (ELISA). Flow cytometry was used to analyze the circulatory number of VEGFR2-expressing cells. The severity of MS was evaluated using the expanded disability status scale (EDSS). Finally, we evaluated the correlation between serum levels of those factors with disease severity. Our findings showed that the serum level of IL-33, IL-37, sVEGFR2 and the circulatory number of VEGFR2-expressing cells were increased in patients with MS compared to healthy subjects (p<0.0001). Also, there was a significant correlation between serum levels of these 3 factors with disease severity according to EDSS. Our study showed that the serum levels of IL-33, IL-37 and sVEGFR2 may be important prognostic biomarkers of MS.

The association of single nucleotide polymorphisms (SNPs) of the IL-7Rα gene with multiple sclerosis (MS) have been documented in various populations. This study aimed to evaluate the genotype distributions of two SNPs, rs6897932 and rs201084372, and the functional association of rs6897932 in relation to IL-7Rα gene expression in a group of Iranian relapsing-remitting MS (RRMS) patients.  Genotyping for both SNPs in the IL7Rα gene and relative quantification of mRNA expression for both isoforms of IL-7Rα were performed in 100 RRMS patients and 100 ethnic-matched healthy controls. Higher significant frequencies of the T allele and TT genotype for rs6897932 (C/T) were observed in patients comparing to controls (p=0.006). Higher frequencies of the T allele and the TT and TG genotypes and lower frequencies of the G allele and GG genotypes for rs201084372 (G/A) were found in patients comparing to controls (p<0.0001).  A decreased level of mRNA expression for the membrane-bound IL-7Rα (mbIL-7Rα) and an increased level of mRNA for the soluble IL-7Rα (sIL-7Rα) were observed in patients versus controls (p=0.005 and p=0.002 respectively). A significant decreased level of mRNA expression for mbIL-7Rα (p=0.01) and an increased level of mRNA for sIL-7Rα (p=0.008) were observed in RRMS patients compared to healthy controls carrying the TT+CT genotypes. The higher levels of mRNA expression for the sIL-7Rα isoform in MS patients carrying the IL7R*TT genotype is a new finding not previously reported in studies on the genotype-induced effects of IL-7Rα expression in multiple sclerosis.

This study aimed to explore the expression of T helper type 1 (Th1)/T helper type 2 (Th2) in herniated nucleus pulposus (NP) and determine their association with sciatic pain. NP was collected from 12 patients with lumbar disc herniation (LDH) (extrusion group) and 6 patients with a vertebral fracture (control group). The expression of Th1/Th2 and related cytokines in the NP was examined by flow cytometry, Western blot, and immunofluorescent staining. Subsequently, an LDH model was established in male Sprague–Dawley rats, and behavioral testings were carried out. The expression of Th1/Th2 and related cytokines in rat NP and the expression of macrophages in the dorsal root ganglia (DRG) were also examined. The number of Th1 cells in rat NP dramatically increased on day 14 after the surgery, but significantly decreased on day 28. The number of Th2 cells increased on day 28. Chemokine ligand 3(CCL3) and CD86 proteins (M1-specific molecules) were expressed at a relatively low level in naive DRG, markedly increased on day 14 after the surgery, and decreased on day 28. Arg1 and CD206 protein (M2-specific molecules) were expressed at a relatively low level in naive DRG and markedly increased on day 28. The mechanical allodynia and heat hyperalgesia developed after NP application and finally partially alleviated. The results suggested that the polarization of Th cells might be involved in the pathogenesis of LDH, and this might be achieved via the phenotypic shift of macrophages.

Autoimmunity represents the attack of the immune system of an organism against its own cells and tissues. Autoimmune diseases may affect one organ (Hashimoto thyroiditis) or can be systemic (chronic urticaria). Many factors are implicated in the pathogenesis of autoimmunity (white cells, cytokines, chemokines). Hashimoto thyroiditis has been associated with chronic urticaria in the last 3 decades in a number of clinical studies. Anti-thyroid antibodies have been documented in a proportion ranging from 10% to 30% in chronic urticaria patients in different countries from 3 continents. Two of the factors involved in the mechanism of autoimmunity are present both in the pathophysiology of Hashimoto thyroiditis and chronic urticaria. According to recent studies, IL6 is implicated in the pathogenesis of both diseases. TregsCD⁴⁺CD²⁵⁺Foxp³⁺ cells have also been implicated in the pathological mechanisms of these 2 entities. This review offers an explanation of the clinical and statistical association between these two diseases from the pathophysiological point of view.

Association between FcεRIB Polymorphisms and Asthma in Asian Population: A Meta-analysis