The Protein Tyrosine Phosphatase Non-Receptor Type 22 (PTPN22) Gene Polymorphism and Susceptibility to Autoimmune Diseases

The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene located on chromosomes 1p 13.3–13 encodes a lymphoid-specific tyrosine phosphatase (Lyp) which is involved in autoimmunity by preventing spontaneous T-cell activation and T-cell development and inactivating T-cell receptor-associated kinases and their substrates. Several single nucleotide polymorphisms (SNPs) have been identified in PTPN22, but only one PTPN22 C1858T has been intensively studied in relation to autoimmune diseases. The PTPN22 C1858T functional polymorphism is a strong non-HLA risk factor for several autoimmune diseases and considered to play an important role in etiology of diseases due to significant production of autoantibodies. However, available literature on PTPN22 C1858T polymorphism and autoimmune diseases shows inconsistencies and ethnic variations. Therefore, further genetic studies on patients suffering from various autoimmune diseases from different ethnicities and PTPN22 gene polymorphisms are expected to help better understand the pathogenesis and will contribute to the development of more targeted therapies and biomarkers

Performance of Polymerase Chain Reaction Techniques Detecting Perforin in the Diagnosis of Acute Renal Rejection: A Meta-Analysis

BACKGROUND: Studies in the past have shown that perforin expression is up-regulated during acute renal rejection, which provided hopes for a non-invasive and reliable diagnostic method to identify acute rejection. However, a systematic assessment of the value of perforin as a diagnostic marker of acute renal rejection has not been performed. We conducted this meta-analysis to document the diagnostic performance of perforin mRNA detection and to identify potential variables that may affect the performance. METHODOLOGY/PRINCIPAL FINDINGS: Relevant materials that reported the diagnostic performance of perforin mRNA detection in acute renal rejection patients were extracted from electronic databases. After careful evaluation of the studies included in this analysis, the numbers of true positive, true negative, false positive and false negative cases of acute renal rejection identified by perforin mRNA detection were gathered from each data set. The publication year, sample origin, mRNA quantification method and housekeeping gene were also extracted as potential confounding variables. Fourteen studies with a total of 501 renal transplant subjects were included in this meta-analysis. The overall performance of perforin mRNA detection was: pooled sensitivity, 0.83 (95% confidence interval: 0.78 to 0.88); pooled specificity, 0.86 (95% confidence interval: 0.82 to 0.90); diagnostic odds ratio, 28.79 (95% confidence interval: 16.26 to 50.97); and area under the summary receiver operating characteristic curves value, 0.9107±0.0174. The univariate analysis of potential variables showed some changes in the diagnostic performance, but none of the differences reached statistical significance. CONCLUSIONS/SIGNIFICANCE: Despite inter-study variability, the test performance of perforin mRNA detected by polymerase chain reaction was consistent under circumstances of methodological changes and demonstrated both sensitivity and specificity in detecting acute renal rejection. These results suggest a great diagnostic potential for perforin mRNA detection as a reliable marker of acute rejection in renal allograft recipients

Value of Doppler Ultrasound Hemodynamics in the Assessment of Renal Artery Stenosis in Transplanted Kidneys: An Assessment of Patients after Percutaneous Transluminal Angioplasty

Doppler ultrasound (USS) may allow a non-invasive early diagnosis of transplant renal artery stenosis (TRAS). Adequate Doppler sampling of the transplant renal artery is difficult, time consuming and highly operator dependent. As a result, there has been increased attention focused on the intrarenal vessels and downstream changes that occur secondary to TRAS. We evaluated Doppler USS parameters in nine patients with TRAS confirmed on angiography (significant stenosis defined as > 60% diameter narrowing). Doppler USS correctly identified all the nine stenoses. Mean peak systolic velocity (PSV) was 3.6 m/s + 1.09. Mean end-diastolic velocity (EDV) was 1.75 m/s + 0.25 with an acceleration time (AT) of 0.14 + 0.04 sec and resistivity index (RI) of 0.42 + 0.12. Early systolic peak (ESP) was lost in all cases. Percutaneous transluminal angioplasty (PTA) was successfully done in five patients with significant improvement in Doppler parameters. PSV decreased from 4.04 m/s + 1.35 to 0.76 m/s + 0.42 (p = 0.01). Similarly EDV improved from 1.71 m/s + 0.28 to 0.30 m/s + 0.17 (p = 0.001). AT improved from 0.13 + 0.01 to 0.05 + 0.01 sec (p = 0.001). RI normalized from 0.34 + 0.07 to 0.73 + 0.09 (p = 0.008). ESP was restored in all the patients. In conclusion: our results show that the Doppler USS analysis of segmental arteries is an excellent tool for the diagnosis of TRAS and follow-up of patients post PTA

The Protein Tyrosine Phosphatase Nonreceptor 22 () R620W Functional Polymorphism in Psoriasis

Background: Psoriasis is a complex autoimmune disease caused by the interaction of genetic and environmental factors. PTPN22 gene polymorphism has been reported to affect psoriasis susceptibility; however, no data are available for Middle Eastern populations. Objective: The aim of this study was to investigate the association of PTPN22 (1858C/T) R620W polymorphism with psoriasis in a Saudi cohort. Methods: Saudi subjects (n = 306) including patients with psoriasis (n = 106) and matched controls (n = 200) were studied for PTPN22 variants using tetra-primer amplification refractory mutation system-polymerase chain reaction method. The frequencies of alleles and genotypes of PTPN22 (1858C/T) polymorphism were compared between patients and controls. Results: The frequency of CT genotype of PTPN22 (1858C/T) polymorphism was significantly higher, whereas that of CC genotype was lower in patients with psoriasis than in controls ( P  < .001, relative risk [RR] = 7.151). The homozygous genotype TT was absent in both the patients and healthy controls. The frequency of allele T encoding tryptophan (W) was significantly increased ( P  < .001, RR = 5.76), whereas that of allele C encoding arginine (R) decreased in psoriasis cases as compared with controls ( P  < .001, RR = 0.173) indicating that individuals carrying allele T are more susceptible to psoriasis than noncarriers. Conclusions: PTPN22 (1858C/T) polymorphism is positively associated with susceptibility of psoriasis in Saudis and can be developed as biomarker for evaluating psoriasis risk. However, further studies on PTPN22 polymorphism in larger samples from different geographical areas and ethnicity are warranted

The Effect of Vitamin E-Modified Dialyzers on Acute Intra-dialytic Symptoms: A Comparative Crossover Study

We performed a crossover study to compare the effect of vitamin E-modified dialyzers on acute intra-dialytic symptoms, with other membranes. Twenty patients on hemodialysis were studied. They were divided into two equal groups of low-flux (C15NL, E15NL) and high-flux (F60, EE15NL) membrane dialyzers. Within each group, a vitamin E-modified dialyzer was compared with another dialyzer in a crossover design over a two-month period. All study patients were seen during each dialysis session by a physician and the occurrence of intra-dialytic symptoms were recorded. There was a significant overall improvement in the incidence of acute intra-dialytic symptoms with the use of vitamin E-modified dialyzers as compared with the other membranes. This effect was more for cuprophane than polysulfone. The occurrence of hypotensive episodes did not differ. Our study indicates that we can achieve a reduction in the incidence of acute intra-dialytic symptoms with the use of vitamin E-modified membrane as compared to cuprophane and polysulfone