Serum Levels Of Alpha-1 Antitrypsin Research Articles

Alpha-1 Antitrypsin Levels and Polymorphisms in Interstitial Lung Diseases.

Alpha-1 antitrypsin deficiency may be a potential predisposing factor for interstitial lung fibrosis. We investigated alpha-1 antitrypsin levels and its polymorphisms in patients with interstitial lung disease. A total of 103 interstitial lung disease patients were compared. The mean alpha-1 antitrypsin level in idiopathic interstitial pneumonia patients was 1.67 ± 0.33 g/L, and it was 1.54 ± 0.37 g/L in patients with nonidiopathic interstitial pneumonia (P = 0.13). Low alpha-1 antitrypsin levels were more frequently observed in nonidiopathic interstitial pneumonia patients compared with idiopathic interstitial pneumonia, but the difference was not statistically significant (8.9% vs. 0%, respectively, P = 0.4). In 100 patients, the normal PiMM genotype was detected, while abnormal ones (PiMZ, n = 2, 1.9%; PiMS, n = 1, 0.97%) were determined in three cases. When the frequency of alpha-1 antitrypsin polymorphism in interstitial lung disease patients was compared with the data of the healthy population, no significant difference was detected for the PiMZ and PiMS variants (P = 0.15 and P = 0.44, respectively). Lower levels of serum alpha-1 antitrypsin were more frequent in nonidiopathic interstitial pneumonia patients than idiopathic interstitial pneumonia without an increase in genetic polymorphism. The difference was not statistically significant.

Disturbed inflammatory/anti-inflammatory milieu and activation of Primary Phase Reactants may underlie Development and Recurrence of First trimester Pregnancy Loss.

Objective: Estimation of serum levels of tumor necrosis factor-a (TNF-a), interleukin (IL-) 6 and 10 and alpha-1 antitrypsin (AAT) in pregnant women with current pregnancy loss (CPL) and non-pregnant women with history of recurrent PL (RPL) compared versus women with normal pregnancy (NP).Patients & Methods: All studied women underwent clinical and vaginal ultrasonographic examination for assurance of inclusion criteria and then gave blood samples for ELISA estimation of studied parameters.Results: Patients of CPL and RPL groups showed significantly high serum TNF-a and IL-6 levels with significantly lower serum IL-10 levels than women of NP group with significant difference between CPL and RPL groups. Serum AAT levels were significantly lower in CPL group than RPL and NP groups with significantly lower levels in RPL than NP group. High serum TNF-a and low AAT levels showed high positive predictive value (PPV) and sensitivity, respectively, for possibility of presence or recurrence of PLConclusion: Disturbed serum levels of pro- and anti-inflammatory cytokines could diagnose CPL with high PPV and persistence of their disturbed levels may predispose to RPL. Activation of primary phase reactant system may underlie, accompany or initiate PL, so low serum AAT during 1st trimester and its persistently low serum levels during inter-pregnancy intervals could be used as screening test for presence or liability for development of PL.

Patterns of chronic inflammation in extensively treated patients with arachnoiditis and chronic intractable pain

ABSTRACTObjective: To use biomarkers to gain insight into and gauge the residual (post-treatment) level of inflammation in two groups of intensively treated patients with severe chronic pain.Methods: Three study groups were analyzed, and included: (i) patients (n = 90) with chronic intractable pain (CIP), (ii) patients (n = 26) with chronic pain and MRI-documented arachnoiditis (ARC) and (iii) normal subjects without a diagnosis of chronic pain (n = 86). We determined and compared the serum concentrations of Alpha-1 Antitrypsin (A1AT), Myeloperoxidase (MPO) and soluble Tumor Necrosis Factor receptor type 2 (sTNFR2) in each of the patient populations studied.Results: Patients treated for ARC or CIP had higher serum levels of A1AT and MPO than normal untreated subjects without a diagnosis of chronic pain. ARC patients had an A1AT mean serum concentration of 167.9 ± 41.9 mg/dL as compared to 148.9 ± 35.2 mg/dL for normal subjects (p = 0.023). CIP patients had the highest mean serum A1AT level 183.6 ± 39.2 mg/dL with p values of <0.0001 or 0.08 when compared to normal subjects or ARC patients respectively. ARC patients had an MPO mean serum concentration of 344.6 ± 227.9 ng/mL as compared to 188.2 ± 107.5 ng/mL for normal subjects (p = < 0.0001). CIP patients had a similar mean serum MPO level of 352.3 ± 164 ng/mL with p values of <0.0001 or 0.85 when compared to normal subjects or ARC patients respectively. In addition, we noted a difference in the pattern of MPO expression in patients with ARC in that 34% had levels of MPO at normal or below and 31% had levels 2-fold or greater than normal.Conclusion: This data supports the concept that in centralized pain, sites of neuroinflammation elaborate MPO and other inflammatory factors which may not be completely cleared from the system despite extensive and complex treatment regimens.

Advances in Identifying Urine/Serum Biomarkers in Alpha-1 Antitrypsin Deficiency for More Personalized Future Treatment Strategies

ABSTRACTAlpha1-antitrypsin deficiency (AATD) is a genetic disorder characterized by reduced serum levels of alpha1-antitrypsin (AAT) and increased risk for developing both early-onset lung emphysema and chronic liver disease. Laboratory diagnosis of AATD is not just a matter of degree, although the AAT serum level is the most important determinant for risk of lung damage. While being a single-gene disease, the clinical phenotype of AATD is heterogeneous. The current standard of care for patients affected by AATD-associated pulmonary emphysema is replacement therapy with weekly i.v. infusions of pooled human purified plasma AAT. Although no treatment for liver disease caused by deposition of abnormal AAT in hepatocytes is available, innovative treatments for this condition are on the horizon.This article aims to provide a critical review of the methodological steps that have marked progress in the detection of indicators described in the literature as being “clinically significant” biomarkers of the disease. The development and routine use of specific biomarkers would help both in identifying which patients and when they are eligible for treatment as well as providing additional parameters for monitoring the disease.

Genotypes, Prevalence and Serum Levels of Alpha-1 Antitrypsin F and I Variants in a Clinical Screening Program

Genotypes, Prevalence and Serum Levels of Alpha-1 Antitrypsin F and I Variants in a Clinical Screening Program

Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil.

ABSTRACTObjective:To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods:This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results, SERPINA1 gene sequencing was performed. Results:Of the 926 COPD patients studied, 85 had DBS AAT levels ≤ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL. Genotype distribution in this subset of 24 patients was as follows: PI*MS, in 3 (12.5%); PI*MZ, in 13 (54.2%); PI*SZ, in 1 (4.2%); PI*SS, in 1 (4.2%); and PI*ZZ, in 6 (25.0%). In the sample as a whole, the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8% Conclusions:The prevalence of AATD in COPD patients in Brazil is similar to that found in most countries and reinforces the recommendation that AAT levels be measured in all COPD patients.

Pulmonary vasculature directed adenovirus increases epithelial lining fluid alpha-1 antitrypsin levels.

Gene therapy for inherited serum deficiency disorders has previously been limited by the balance between obtaining adequate expression and causing hepatic toxicity. Our group has previously described modifications of a replication deficient human adenovirus serotype 5 that increase pulmonary vasculature transgene expression. In the present study, we use a modified pulmonary targeted adenovirus to express human alpha-1 antitrypsin (A1AT) in C57BL/6 J mice. Using the targeted adenovirus, we were able to achieve similar increases in serum A1AT levels with less liver viral uptake. We also increased pulmonary epithelial lining fluid A1AT levels by more than an order of magnitude compared to that of untargeted adenovirus expressing A1AT in a mouse model. These gains are achieved along with evidence of decreased systemic inflammation and no evidence for increased inflammation within the vector-targeted end organ. In addition to comprising a step towards clinically viable gene therapy for A1AT, maximization of protein production at the site of action represents a significant technical advancement in the field of systemically delivered pulmonary targeted gene therapy. It also provides an alternative to the previous limitations of hepatic viral transduction and associated toxicities.

Recombinant Adeno-Associated Virus Vector Genomes Take the Form of Long-Lived, Transcriptionally Competent Episomes in Human Muscle.

Gene augmentation therapy as a strategy to treat alpha-1 antitrypsin (AAT) deficiency has reached phase 2 clinical testing in humans. Sustained serum levels of AAT have been observed beyond one year after intramuscular administration of a recombinant adeno-associated virus (rAAV) vector expressing the AAT gene. In this study, sequential muscle biopsies obtained at 3 and 12 months after vector injection were examined for the presence of rAAV vector genomes. Each biopsy sample contained readily detectable vector DNA, the majority of which existed as double-stranded supercoiled and open circular episomes. Episomes persisted through 12 months, although at slightly lower levels than observed at 3 months. There was a clear dose response when comparing the low- and mid-vector-dose groups to the high-dose group. The highest absolute copy numbers were found in a high-dose subject, and serum AAT levels at 12 months confirmed that the high-dose group also had the highest sustained serum AAT levels. Sequence analysis revealed that the vast majority of episomes contained double-D inverted terminal repeats ranging from fully intact to severely deleted. Molecular clones of vector genomes derived directly from the biopsies were transcriptionally active, potentially identifying them as the source of serum AAT in the trial subjects.

Déficit en alpha-1 antitrypsine secondaire à une mutation Null

Alpha-1antitrypsin deficiency is a hereditary disease defined at the biological level by a serum alpha-1antitrypsin level below 11μM/L. The null variants are characterized by undetectable circulating alpha-1antitrypsin levels. Suspicion of a null variant requires the use of appropriate diagnostic techniques. We report the case of a 33-year old patient presenting with dyspnea on exertion, associated with a moderate airflow obstruction, incompletely reversible. His tobacco use was less than 3pack-years. The thoracic CT-scan showed emphysema. The serum alpha-1antitrypsin level was collapsed. Phenotyping by isoelectrofocusing on agarose gels did not show any band. The study of the SERPINA1gene, by PCR-sequence of the II, III, IV and V exons and the flanking intronic sequences, allowed identification of the NullQ0ourém allele in homozygous state. This mutation was found in heterozygous state in both parents of the index case and in one of his brothers. The index case showed a rapid aggravation of the airflow obstruction. In the case of a serum alpha-1antitrypsin deficiency, the analysis of the phenotype of the protein by isoelectrofocusing must be performed as a first-line investigation. The detection of an atypical profile may suggest the presence of deficient alleles other than the PI S and PI Z alleles that can only be characterized by sequencing of the whole SERPINA1gene. The patients carrying a null mutation have a high risk of severe chronic obstructive pulmonary disease.

Alpha-1 Antitrypsin Deficiency in COPD Patients: A Cross-Sectional Study

IntroductionAlpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with early onset chronic obstructive pulmonary disease (COPD) and liver disease. It is also a highly under-diagnosed condition. As early diagnosis could prompt specific interventions such as smoking cessation, testing of family members, genetic counseling and use of replacement therapy, screening programs are needed to identify affected patients. ObjectiveTo estimate the prevalence of severe AATD in COPD patients by routine dried blood spot testing and subsequent genotyping in patients with alpha-1 antitrypsin (AAT) levels below an established threshold. Materials and methodsCross-sectional study of adult COPD patients attending the Hospital Dr. Antonio Cetrángolo (Buenos Aires, Argentina) between 2009 and 2012. The study consisted of capillary blood collection via finger stick to determine AAT levels, clinical evaluation and lung function tests. Genotype was determined in AAT-deficient patients. ResultsA total of 1002 patients were evaluated, of whom 785 (78.34%) had normal AAT levels, while low AAT levels were found in 217 (21.66%). Subsequent genotyping of the latter sub-group found: 15 (1.5%, 95% CI 0.75–2.25) patients with a genotype associated with severe AATD, of whom 12 were ZZ (1.2%, 95% CI 0.52–1.87) and 3 SZ (0.3%, 95% CI 0–0.64). The remaining 202 patients were classified as: 29 Z heterozygotes (2.89%, 95% CI 1.86–3.93), 25 S heterozygotes (2.5%, 95% CI 1.53–3.46) and 4 SS (0.4%, 95% CI 0.01–0.79). A definitive diagnosis could not be reached in 144 patients (14.37%, 95% CI 12.2–16.54). ConclusionThe strategy using an initial serum AAT level obtained by dried blood spot testing and subsequent genotyping was a satisfactory initial approach to a screening program for severe AAT, as a definitive diagnosis was achieved in 87% of patients. However, results were not obtained for logistical reasons in the remaining 13%. This major obstacle may be overcome by the use of dried blood spot phenotyping techniques. We believe this approach for detecting AATD in COPD patients, in compliance with national and international guidelines, is supported by our results.

Challenges and Prospects for Alpha-1 Antitrypsin Deficiency Gene Therapy.

Alpha-1 antitrypsin (AAT) is a protease inhibitor belonging to the serpin family. A number of identified mutations in the SERPINA1 gene encoding this protein result in alpha-1 antitrypsin deficiency (AATD). A decrease in AAT serum concentration or reduced biological activity causes considerable risk of chronic respiratory and liver disorders. As a monogenic disease, AATD appears to be an attractive target for gene therapy, particularly for patients with pulmonary dysfunction, where augmentation of functional AAT levels in plasma might slow down respiratory disease development. The short AAT coding sequence and its activity in the extracellular matrix would enable an increase in systemic serum AAT production by cellular secretion. In vitro and in vivo experimental AAT gene transfer with gamma-retroviral, lentiviral, adenoviral, and adeno-associated viral (AAV) vectors has resulted in enhanced AAT serum levels and a promising safety profile. Human clinical trials using intramuscular viral transfer with AAV1 and AAV2 vectors of the AAT gene demonstrated its safety, but did not achieve a protective level of AAT >11 μM in serum. This review provides an in-depth critical analysis of current progress in AATD gene therapy based on viral gene transfer. The factors affecting transgene expression levels, such as site of administration, dose and type of vector, and activity of the immune system, are discussed further as crucial variables for optimizing the clinical effectiveness of gene therapy in AATD subjects.

Three missense variants of metabolic syndrome-related genes are associated with alpha-1 antitrypsin levels.

Alpha-1 antitrypsin (AAT) encoded by SERPINA1 is an acute-phase inflammation marker, and AAT deficiency (AATD) is known as one of the common genetic disorders in European populations. However, no genetic determinants to AAT levels apart from the SERPINA gene clusters have been identified to date. Here we perform a genome-wide association study of serum AAT levels followed by a two-staged replication study recruiting a total of 9,359 Japanese community-dwelling population. Three missense variants of metabolic syndrome-related genes, namely, rs671 in ALDH2, rs1169288 in HNF1A and rs1260326 in GCKR, significantly associate with AAT levels (P≤1.5 × 10−12). Previous reports have shown the functional relevance of ALDH2 and HNF1A to AAT. We observe a significant interaction of rs671 and alcohol consumption on AAT levels. We confirm the association between AAT and rs2896268 in SERPINA1, which is independent of known causative variants of AATD. These findings would support various AAT functions including metabolic processes.

Alternative transcripts of the SERPINA1 gene in alpha-1 antitrypsin deficiency.

BackgroundSERPINA1 is the gene for alpha-1 antitrypsin (AAT), an acute phase protein with anti-protease and immunoregulatory activities. Mutations in SERPINA1 gene cause AAT deficiency and predispose individuals to early-onset emphysema and liver diseases. Expression of the SERPINA1 gene is regulated by different promoters and alternative splicing events among non-coding exons 1A, 1B and 1C.MethodsWe have developed three quantitative PCR (QT-PCR) assays (1A, 1B and 1C). These assays were applied for the analysis of SERPINA1 alternative transcripts in: (1) 16 human tissues and (2) peripheral blood leukocytes from 33 subjects with AAT mutations and 7 controls.ResultsTissue-specific expression was found for the SERPINA1 transcripts. The 1A transcripts were mainly expressed in leukocytes and lung tissue while those detected with the 1B assay were highly restricted to leukocytes. Only 1B transcripts significantly correlated with serum AAT levels. The 1C transcripts were specifically found in lung, liver, kidney and pancreas. Furthermore, the expression of transcripts was related to AAT genotypes. While deficient variants of AAT had no pronounced effect on the transcript expression, null alleles were associated with significant reduction of different transcripts.ConclusionsThe possibility to discriminate between SERPINA1 alternative splicing products will help us to understand better the regulation of SERPINA1 gene and its association with SERPINA1 mutations-related diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0585-y) contains supplementary material, which is available to authorized users.

333. Simultaneous Disruption of Five SerpinA1 Genes in Mice Using CRISPR/Cas9 to Generate the First Animal Model of Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency is a common autosomal co-dominant genetic disorder. This condition affects up to 1:2500 individuals of European ancestry, leading to the development of lung and in certain cases liver disease. AAT, as a member of the serpin family, is a protease inhibitor predominantly synthesized in the liver. Upon secretion into the blood stream, AAT's principle physiological role occurs in the lungs where it inactivates excess neutrophil elastase, thereby preventing potential damage to the alveoli. In humans, a glutamate to lysine change at position 342 of the protein, known as a PiZ mutation, accounts for over 90% of cases. This and other mutations lead to reduced serum levels of AAT in addition to reduced protein function. With time, the decreased levels of AAT allows for unopposed neutrophil elastase activity, causing the eventual breakdown of alveolar elastin thus resulting in emphysema. Currently, a serum deficient genetic animal model simulating the lung condition does not exist, which severely limits the development of innovative therapeutics.Our goal is to use CRISPR/Cas9 technology to generate an AAT knock-out mouse to study the pulmonary disease. Unlike humans, mice have five highly conserved tandem copies of the serpinA1 gene. This phenomenon has made it difficult to create knockout mice using traditional approaches. With the advent of novel genome editing techniques, this problem has reached a feasible threshold. To this end, we designed four guide RNA (gRNA) constructs to target conserved regions within all 5 copies of the serpinA genes. The gRNA constructs were initially evaluated using a single strand annealing assay. By co-transfecting a gRNA/Cas9 complex with appropriate reporters, the intensity of resulting GFP measured target efficiency. Afterwards, embryonic stem cell transfection and zygote microinjection were used to deliver the genome editing complex for in vitro and in vivo studies.During the screening process, 200 embryonic stem cell samples and 40 transgenic mice were evaluated by quantifying AAT serum levels and sequencing specific target regions within the genome. Upon completion, several knock-outs were identified and founder lines were established.Ongoing studies aim to determine the susceptibility of developing emphysema after challenging the knockout mice with porcine pancreatic elastase. We expect the mice will display a distinguishable pulmonary phenotype, aside from decreased levels of AAT as determined by ELISA, which will allow for the characterization of airway pathophysiology. This mouse model is of particular clinical significance as it presents the first opportunity to test current and novel therapeutics aimed at augmenting serum levels of AAT.

Déficit de alfa 1 antitripsina en pacientes con EPOC: estudio de corte transversal

IntroductionAlpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with early onset chronic obstructive pulmonary disease (COPD) and liver disease. It is also a highly under-diagnosed condition. As early diagnosis could prompt specific interventions such as smoking cessation, testing of family members, genetic counselling and use of replacement therapy, screening programs are needed to identify affected patients. ObjectiveTo estimate the prevalence of severe AATD in COPD patients by routine dried blood spot testing and subsequent genotyping in patients with alpha-1 antitrypsin (AAT) levels below an established threshold. Materials and methodsCross-sectional study of adult COPD patients attending the Hospital Dr. Antonio Cetrángolo (Buenos Aires, Argentina) between 2009 and 2012. The study consisted of capillary blood collection via finger stick to determine AAT levels, clinical evaluation and lung function tests. Genotype was determined in AAT-deficient patients. ResultsA total of 1,002 patients were evaluated, of whom 785 (78.34%) had normal AAT levels, while low AAT levels were found in 217 (21.66%). Subsequent genotyping of the latter sub-group found: 15 (1.5%, 95% CI 0.75-2.25) patients with a genotype associated with severe AATD, of whom 12 were ZZ (1.2%, 95% CI 0.52-1.87) and 3 SZ (0.3%, 95% CI 0-0.64). The remaining 202 patients were classified as: 29 Z heterozygotes (2.89%, 95% CI 1.86-3.93), 25 S heterozygotes (2.5%, 95% CI 1.53-3.46) and 4 SS (0.4%, 95% CI 0.01-0.79). A definitive diagnosis could not be reached in 144 patients (14.37%, 95% CI 12.2-16.54). ConclusionThe strategy using an initial serum AAT level obtained by dried blood spot testing and subsequent genotyping was a satisfactory initial approach to a screening program for severe AAT, as a definitive diagnosis was achieved in 87% of patients. However, results were not obtained for logistical reasons in the remaining 13%. This major obstacle may be overcome by the use of dried blood spot phenotyping techniques. We believe this approach for detecting AATD in COPD patients, in compliance with national and international guidelines, is supported by our results.

Low serum levels of alpha1 anti-trypsin (α1-AT) and risk of airflow obstruction in non-primary α1-AT-deficient patients with compensated chronic liver disease.

BackgroundAlpha1 anti-trypsin (α1-AT), a serine protease inhibitor synthesized in the liver, is a major circulating antiprotease that provides defense against proteolytic damage in several tissues. Its deficiency is associated with airflow obstruction. The present study aimed to explore the role of α1-AT as a biomarker of airflow performance in chronic liver disease (CLD).Material/MethodsSerum α1-AT levels and lung function (spirometry) were evaluated in non-primary α1-AT-deficient, alcoholic CLD patients without evident respiratory limitations.ResultsThirty-four patients with airflow obstruction (n=11), airflow restriction (n=12), and normal airflow (n=11, age-matched controls) were eligible. α1-AT was decreased in the airflow obstruction group. ROC-cutoff α1-AT=24 mg/dL effectively discriminated airflow obstruction (AUC=0.687) and was associated with a 10-fold higher risk (p=0.0007).ConclusionsLower α1-AT increased the risk of airflow obstruction in CLD patients without primary α1-AT deficiency.

The Natural History of Lung Function in Severe Deficiency of Alpha-1 Antitrypsin Following Orthotopic Liver Transplantation: A Case Report.

PI*ZZ alpha-1 antitrypsin (AAT) deficiency poses risk for lung disease through 2 different mechanisms: a toxic loss of function in which deficient AAT levels cause a depleted proteolytic screen and, separately, a proinflammatory effect of Z polymers produced both by alveolar macrophages and by the liver. Ample data support the first mechanism, while the possible contribution of the second 2 proinflammatory mechanisms is currently unknown. Experience with a 74 year-old PI*ZZ female who underwent single lung transplantation and subsequent orthotopic liver transplantation (OLT) may shed light on the relative contributions of each of the potential mechanisms. Availability of multiple pulmonary function tests (PFT) measurements uniquely permitted calculation of rates of lung function change before and after OLT. The rate of forced expiratory volume in 1 second (FEV1) decline normalized post-OLT (from -60 to -21 ml/yr). Her course suggests that restoring the normal serum AAT levels or, alternately, eliminating liver-derived polymers, exerted a greater effect on preventing emphysema progression than local Z polymer production contributed to furthering emphysema.

Alpha – 1 antitrypsin in smokers and non smokers chronic obstructive pulmonary disease

Aim: The aim of the present study is to correlate and compare alpha-1 antitrypsin level in smoker and non smoker chronic obstructive pulmonary disease patients. Material and Methods: A comparative study was carried out in 200 subjects, more than 40 years of age and having chronic obstructive pulmonary disease for more than 1 year with a history of smoking at least 20 cigarettes per day (Group A) and without a history of smoking (Group B). Pulmonary function tests were used to diagnose the disease as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. Alpha-1 antitrypsin level was done by turbidimetry method on fully auto analyzer I-Lab 650 (Instrumentation Laboratory, USA) at Clinical Biochemistry Section, Laboratory Services Sir Takhtsinhji Hospital, Bhavnagar. Statistical analysis was done by using unpaired t-test and Pearson’s correlation coefficient. Results: Results of present study shows that alpha-1 antitrypsin level was decreased in smoker chronic obstructive pulmonary disease patients (150.83±18.853) when compared to non smokers (183.97±29.383). There was statistically significant difference in alpha-1 antitrypsin level between the two groups with ‘p’ value of <0.0001. Pearson’s correlation test show negative correlation between smoker and nonsmoker chronic obstructive pulmonary disease patients. Conclusion: The values of serum alpha-1 antitrypsin levels were more significantly decreased in smokers indicating an important role of smoking in pathogenesis of chronic obstructive pulmonary disease. Alpha-1 antitrypsin can act as a predictor for future development of chronic obstructive pulmonary disease in smokers and in nonsmokers.

Diabetic retinopathy: could the alpha-1 antitrypsin be a therapeutic option?

Diabetic retinopathy is one of the most important causes of blindness. The underlying mechanisms of this disease include inflammatory changes and remodeling processes of the extracellular-matrix (ECM) leading to pericyte and vascular endothelial cell damage that affects the retinal circulation. In turn, this causes hypoxia leading to release of vascular endothelial growth factor (VEGF) to induce the angiogenesis process. Alpha-1 antitrypsin (AAT) is the most important circulating inhibitor of serine proteases (SERPIN). Its targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, proteinase 3 (PR-3) and plasminogen activator (PAI). AAT modulates the effect of protease-activated receptors (PARs) during inflammatory responses. Plasma levels of AAT can increase 4-fold during acute inflammation then is so-called acute phase protein (APPs). Individuals with low serum levels of AAT could develop disease in lung, liver and pancreas. AAT is involved in extracellular matrix remodeling and inflammation, particularly migration and chemotaxis of neutrophils. It can also suppress nitric oxide (NO) by nitric oxide sintase (NOS) inhibition. AAT binds their targets in an irreversible way resulting in product degradation. The aim of this review is to focus on the points of contact between multiple factors involved in diabetic retinopathy and AAT resembling pleiotropic effects that might be beneficial.Electronic supplementary materialThe online version of this article (doi:10.1186/0717-6287-47-58) contains supplementary material, which is available to authorized users.

Serum transferrin as a liver fibrosis biomarker in patients with chronic hepatitis B.

Background/AimsTransferrin and alpha-1 antitrypsin are reportedly associated with liver fibrosis. We evaluated the usefulness of serum transferrin and alpha-1 antitrypsin as new liver fibrosis markers in patients with chronic hepatitis B.MethodsThe study included 293 patients with chronic hepatitis B who underwent a liver biopsy between October 2005 and June 2009, and who had no history of hepatocellular carcinoma. Serum markers and liver fibrosis stages were compared.ResultsUnivariate analysis revealed that age (P<0.001), serum platelet count (P<0.001), and serum alkaline phosphatase level (P=0.003) differed significantly between the patients with and without liver cirrhosis. Serum transferrin levels were significantly lower in advanced fibrosis than in mild fibrosis in both univariate analysis (P=0.002) and multivariate analysis (P=0.009). In addition, the serum transferrin level was significantly lower in cirrhotic patients than in noncirrhotic patients (P=0.020). However, the serum level of alpha-1 antitrypsin was not significantly associated with liver cirrhosis in patients with chronic hepatitis B.ConclusionsSerum transferrin could be promising serum marker for predicting advanced liver fibrosis in patients with chronic hepatitis B.