TGF-ß1 Gene Polymorphism and Its Correlation with Serum Level of TGF-ß1 in Psoriasis Vulgaris Among Iraqi People.

PURPOSE: Many cytokines have been implicated in the pathogenesis of psoriasis, among these the transforming growth factor-beta 1 (TGF-ß1) can be endorsed by different mechanisms besides inhibiting keratinocytes proliferation. The role of genetic polymorphisms of TGF-ß1 has been studied in various inflammatory diseases. Our aim is to study the correlation of TGF-ß1 gene polymorphism at codon 10 and 25 with the expression of serum level of TGF-ß1 in a sample of Iraqi psoriatic patients compared to the control group. MATERIALS AND METHODS: A cross-sectional study involved 100 patients with psoriasis vulgaris and 50 sex- and age-matched healthy volunteers as control group. Serum and genomic DNA were prepared from peripheral blood samples. Amplification refractory mutation system-polymerase chain reaction technique (ARMS-PCR) had been applied for genotyping TGF-ß1 codon 10 [rs1982073] and codon 25 [rs1800471] genetic polymorphisms. Enzyme-linked immunosorbent assay technique (ELISA) based on the sandwich principle was used for quantification of serum TGF-ß1 level. Psoriasis Area and Severity Index (PASI) scoring was applied for determining the severity in psoriatic patients and classified accordingly to mild (PASI<7), moderate (PASI 7-12), severe (PASI>12) groups. RESULTS: Statistically significant difference was found in TGF-ß1 gene polymorphism between psoriatic patients and control group at codon 10 (T869C) polymorphism (p=0.021) and codon 25 (G915C) polymorphism (p=0.040). No significant association was detected with the mean serum TGF-ß1 level, severity of the disease, disease onset, gender, history of psoriatic arthritis, and smoking in both codons. Significant lower mean serum TGF-ß1 level was found among psoriatic group (192.17 ± 531.12 ng/L) compared with controls (565.89 ± 1372.30 ng/L) (p = 0.018). Relation of mean serum TGF-ß1 level with the onset of the disease was statistically significant (p = 0.004), early-onset disease group was lower (105.92 ± 68.02 ng/L) compared with the late-onset disease group (450.92 ±1027.79 ng/L). The mean serum TGF-ß1 level showed no significant differences with the severity of psoriasis, gender, history of psoriatic arthritis, and smoking. CONCLUSION: Iraqi population showed a significant association between TGF-ß1 gene polymorphism at codon 10 and 25 were with psoriasis susceptibility, and a significantly lower mean serum TGF-ß1 level was detected in psoriatic patients.

Proteome of human plasma very low-density lipoprotein and low-density lipoprotein exhibits a link with coagulation and lipid metabolism.

Apart from transporting lipids through the body, the human plasma lipoproteins very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) are also thought to serve as a modality for intra-organismal protein transfer, shipping proteins with important roles in inflammation and thrombosis from the site of synthesis to effector locations. To better understand the role of VLDL and LDL in the transport of proteins, we applied a combination of LTQ ORBITRAP-XL (nLC-MS/MS) with both in-SDS-PAGE gel and in-solution tryptic digestion of pure and defined VLDL and LDL fractions. We identified the presence of 95 VLDL- and 51 LDL-associated proteins including all known apolipoproteins and lipid transport proteins, and intriguingly a set of coagulation proteins, complement system and anti- microbial proteins. Prothrombin, protein S, fibrinogen γ, PLTP, CETP, CD14 and LBP were present on VLDL but not on LDL. Prenylcysteine oxidase 1, dermcidin, cathelicidin antimicrobial peptide, TFPI-1 and fibrinogen α chain were associated with both VLDL and LDL. Apo A-V is only present on VLDL and not on LDL. Collectively, this study provides a wealth of knowledge on the protein constituents of the human plasma lipoprotein system and strongly supports the notion that protein shuttling through this system is involved in the regulation of biological processes. Human diseases related to proteins carried by VLDL and LDL can be divided in three major categories: 1 - dyslipidaemia, 2 - atherosclerosis and vascular disease, and 3 - coagulation disorders.

Donor chimera model for tolerance induction in transplantation.

Tolerance induction is the basis of a successful transplantation with the goal being the re-establishment of homeostasis after transplantation. Non-autograft transplantation disrupts this maintenance drastically which would be avoided by administration of a novel procedure. At present, the blood group antigens and the genotypes of the donor and recipient are cross-matched before transplantation combined with a drug regimen that confers general immunosuppression. But the 'specific' unresponsiveness of the recipient to the donor organ, implied by 'tolerance', is not achieved in this process. This article introduces the 'donor chimera model' via the concept of the 'closed transplantation loop' approach for tolerance induction which seeks to limit the use of immunosuppressive therapy after transplantation.