Unique and shared systemic biomarkers for emphysema in Alpha-1 Antitrypsin deficiency and chronic obstructive pulmonary disease.

BACKGROUND: Alpha-1 Antitrypsin (AAT) deficiency (AATD), the most common genetic cause of emphysema presents with unexplained phenotypic heterogeneity in affected subjects. Our objectives to identify unique and shared AATD plasma biomarkers with chronic obstructive pulmonary disease (COPD) may explain AATD phenotypic heterogeneity. METHODS: The plasma or serum of 5,924 subjects from four AATD and COPD cohorts were analyzed on SomaScan V4.0 platform. Using multivariable linear regression, inverse variance random-effects meta-analysis, and Least Absolute Shrinkage and Selection Operator (LASSO) regression we tested the association between 4,720 individual proteins or combined in a protein score with emphysema measured by 15th percentile lung density (PD15) or diffusion capacity (DLCO) in distinct AATD genotypes (Pi*ZZ, Pi*SZ, Pi*MZ) and non-AATD, PiMM COPD subjects. AAT SOMAmer accuracy for identifying AATD was tested using receiver operating characteristic curve analysis. FINDINGS: In PiZZ AATD subjects, 2 unique proteins were associated with PD15 and 98 proteins with DLCO. Of those, 68 were also associated with DLCO in COPD also and enriched for three cellular component pathways: insulin-like growth factor, lipid droplet, and myosin complex. PiMZ AATD subjects shared similar proteins associated with DLCO as COPD subjects. Our emphysema protein score included 262 SOMAmers and predicted emphysema in AATD and COPD subjects. SOMAmer AAT level <7.99 relative fluorescence unit (RFU) had 100% sensitivity and specificity for identifying Pi*ZZ, but it was lower for other AATD genotypes. INTERPRETATION: Using SomaScan, we identified unique and shared plasma biomarkers between AATD and COPD subjects and generated a protein score that strongly associates with emphysema in COPD and AATD. Furthermore, we discovered unique biomarkers associated with DLCO and emphysema in PiZZ AATD. FUNDING: This work was supported by a grant from the Alpha-1 Foundation to RPB. COPDGene was supported by Award U01 HL089897 and U01 HL089856 from the National Heart, Lung, and Blood Institute. Proteomics for COPDGene was supported by NIH 1R01HL137995. GRADS was supported by Award U01HL112707, U01 HL112695 from the National Heart, Lung, and Blood Institute, and UL1TRR002535 to CCTSI; QUANTUM-1 was supported by the National Heart Lung and Blood Institute, the Office of Rare Diseases through the Rare Lung Disease Clinical Research Network (1 U54 RR019498-01, Trapnell PI), and the Alpha-1 Foundation. COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion.

High incidence of tobacco streak virus in the tobacco fields of Iran.

Currently the northern provinces of Iran (Mazandaran, Golestan and Gilan) are the main tobacco growing regions in the country and this crop has an special importance in the national economy. Three tobacco types including flue-cured (mainly Coker 347 and some Virginia E1), burley (Burley 21) and oriental (Basma 178-2) are presently grown in these regions. Epidemics of viral diseases have occurred during the recent years in many tobacco fields in these areas. The quality of tobacco products which is much important, is adversely affected by plant pathogens specially viruses. In a survey on the viruses of tobacco, the fields in these regions were inspected and leaf samples from symptomatic plants were collected. Some plants had one or more of the symptoms such as dentate leaf margin, thicker leaf tissue and necrotic areas on the stem. The samples were tested for TSV infection by the DAS-ELISA method (Clark and Adams, 1977) using polyclonal antibody (AS-0615, DSMZ, Germany). TSV was detected in more than 79% of all tobacco samples from these three provinces. The TSV infection level among the tested samples was 86.8% in Gilan (Rasht, Bazar-Jomeh and Talesh), 82.3% in Mazandaran (Behshahr, Sari, Neka and Sourak) and 71.8% in Golestan (Gorgan, Aliabad and Minoodasht). No significant difference was seen among the infection levels for the mentioned commercial varieties and also some other tested varieties such as C176, K326 and MN944. It seems that there is no resistance sources against this virus within these varieties. Also the results of tests for TSV were similar in two consecutive years (2004 and 2005). It should be added that not all of the TSV infected plants showed the stated symptom types. Many of the TSV infected samples had mixed infections with one or more other viruses such as TSWV, CMV, PVY and TMV and there was almost no sample with a single TSV infection. This is the first report on the occurrence and distribution of TSV in the tobacco fields of Iran, too.

Identification of PVY-N on potato and tobacco in Tehran and Mazandaran provinces.

During two growing seasons in years of 2003 and 2004 potato and tobacco of virus infected plants were collected from fields in Tehran (Damavand) and Mazandaran (Behshahr) provinces. Serological methods of TAS-ELISA and DIBA were performed by using PVY antiserum (DSMZ - Plant Virus Collection; Germany) but only PVY was detected. The strain of samples was determined by using MAb of potato virus Y (AS-0403/1; DSMZ; Germany). The molecular weight of the virus coat protein was approximately 34 kDa in SDS-PAGE and Western blotting. Total RNA was extracted for RT-PCR. Immunocapture RT-PCR and RT-PCR products were 974 bp by using specific primers of PVY. IC-RT-PCR has given the best results.