Autoantibodies as predictors of disease: the clinical and experimental evidence.

Several studies have shown that autoimmune diseases are preceded by a long pre-clinical phase, and that many autoantibodies can be detected in the serum of asymptomatic subjects years before the clinical manifestations become evident. Tests for these autoantibodies could therefore be used in principle in screening studies on unselected populations to identify individuals predisposed to the development of the disease at an early stage, and start treatment or adopt preventive measures where possible. This aspect has aroused particular interest, as multiplex investigation techniques are already available, and microarray methods are under development, which will probably allow tens or hundreds of autoantibodies to be measured simultaneously.

Antibodies to citrullinated peptides: a significant step forward in the early diagnosis of rheumatoid arthritis.

The early diagnosis of rheumatoid arthritis (RA) has become a priority owing to the availability of effective disease-modifying agents that can improve patient wellbeing and influence the clinical outcome. However, this represents a real challenge, as no clinical, radiological or immunological features are pathognomonic at the time of presentation. For this reason, development of the anti-cyclic citrullinated peptide (CCP) antibody assay, a highly disease-specific serological marker for RA, has been a great step forward for the rheumatologist and the clinical laboratory.

Low specificity of anti-tissue transglutaminase antibodies in patients with primary biliary cirrhosis.

The association between celiac disease (CD) and primary biliary cirrhosis (PBC) is well documented in medical literature; however, a high frequency of false positive results of the anti-transglutaminase (anti-tTG) test has been reported in patients with PBC. To verify if the positive results for anti-tTG autoantibody are false positives due to cross reactivity with mitochondrial antigens, we studied 105 adult patients affected with PBC, positive for anti-mitochondrial M2 antibodies. Anti-tTG IgA antibodies were studied by using six different immunoenzymatic assays that employ the tTG antigen obtained from different sources (human recombinant, placenta, red blood cells, and guinea pig liver).

[Celiac disease, laboratory updates].

A celiac disease update review and a case report are presented, especially concerning a Clinical Pathology Laboratory approach. Implemented basic research, case finding strategy and information technologies are the key tools for a better understanding of the multi-etiological features of this disease. By these tools it will be achieved appropriateness in diagnosing and monitoring of the related clinical pictures.

A prospective study of 1038 pregnancies on the predictive value of anti-annexin V antibodies for fetal loss.

Retrospective studies have demonstrated that anti-annexin V (anti-AnxV) antibodies are linked to miscarriage. Their predictive value is, however, unknown. We have carried out a prospective study to evaluate the relationship between anti-AnxV antibodies and the pregnancy outcome.

Proteomic: new advances in the diagnosis of rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting the joints. A number of novel treatment modalities have been introduced over the past years, and rheumatologists are now attempting to institute optimal treatment in recent-onset arthritis. To facilitate diagnosis during the early stages of disease, when often not all clinical symptoms are manifest, a good serological marker is needed.

Prevalence and clinical correlation of anti-phospholipid-binding protein antibodies in anticardiolipin-negative patients with systemic lupus erythematosus and women with unexplained recurrent miscarriages.

Context: Anti-phospholipid antibodies (aPL) are a heterogeneous group of autoantibodies, the presence of which is associated with thrombotic events and miscarriage.

Objective: To establish whether antibodies directed against phospholipid-binding plasma proteins such as beta(2)-glycoprotein I (beta(2)GPI), prothrombin (PT), and annexin V (Anx V) constitute a risk factor for thromboembolism in patients with systemic lupus erythematosus (SLE) and for miscarriage in women with recurrent pregnancy loss (RPL), independently of the presence of the classic anticardiolipin (aCL) antibodies, and whether their determination together with that of aCL would help to increase the diagnostic sensitivity of aPL tests.

Design: The prevalence of various antibodies directed toward phospholipids (CL and other anionic phospholipids [APL]) and phospholipid-binding proteins (beta(2)GPI, PT, and Anx V) was determined by immunoenzymatic methods in 311 serum samples.

IgA and IgG tissue transglutaminase antibody prevalence and clinical significance in connective tissue diseases, inflammatory bowel disease, and primary biliary cirrhosis.

An association between celiac disease (CD) and other autoimmune diseases such as connective tissue diseases (CTD), inflammatory bowel diseases (IBD), and primary biliary cirrhosis (PBC) has been reported in several studies. However, a high rate of false positives in autoantibody testing was noted, especially when tissue transglutaminase (tTG) from guinea pig liver was used. Thus, the real prevalence of CD in CTD, IBD, and PBC is unclear.

Association of celiac disease with connective tissue diseases and autoimmune diseases of the digestive tract.

Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten in susceptible individuals, and is one of the most frequent genetically based diseases, with a prevalence of 1:200 in the general population. The association between CD and connective tissue diseases (CTD) and autoimmune diseases of the digestive tract (DT) has been described in several case reports but in few extensive studies, with varying prevalence. A high rate of false positive results were observed when low specific tests, such as the anti-gliadin and the guinea pig tissue transglutaminase (tTG) antibody assays were used.

Application of a diagnostic algorithm in autoantibody testing: assessment of clinical effectiveness and economic efficiency.

Background: Guidelines aim to assist physicians about appropriate health care for specific clinical circumstances. Therefore, they must be continuously updated, integrated and tailored to local situations.

Methods: We applied recently developed guidelines for autoantibody testing by assessing their economic (efficiency) and clinical (effectiveness) impact.

Fusion between homologous cells, modified epigenetic environment and possible cell cancerization.

For a long time now we have been putting forwards the hypothesis that, when two cells belonging to different tissues of the same organism fuse, the nucleous/nuclei of the resulting "fused" cell could lay into a cytoplasm possibly containing factors influencing the activation or deactivation of genes able to interfere with the differentiation "iter" proper of the parent cells. As a consequence, the fused cells could undergo neoplastic transformation. In order to give an experimental support to such an hypothesis, mononuclear cells and granulocytes were isolated from the white blood cells of the same individual, mixed (at 1/1 ratio) and fused, using polyethylen glycol (PEG).

Autoantibody detection in scleroderma patients. Diagnostic and analytical performances of a new coupled particle light scattering immunoassay.

Objective: We evaluated the diagnostic and analytical performance of the Coupled Particle Light Scattering technology applied to the detection of anti-topoisomerase I (anti-Scl70) and anti-CENP-B autoantibodies.

Methods: The Scl70 antigen was obtained by recombinant DNA procedures using a prokaryotic expression system; CENP-B was a Baculovirus-expressed recombinant protein. Anti-centromere and anti-Scl70 antibodies were assayed in serum samples from 288 patients, of whom 123 had systemic sclerosis/scleroderma and 165 constituted the control groups (including patients with other connective tissue diseases, viral infections, Lyme disease, and healthy subjects).

New coupled-particle light-scattering assay for detection of Ro/SSA (52 and 60 kilodaltons) and La/SSB autoantibodies in connective tissue diseases.

The diagnostic and analytical performance of the coupled-particle light-scattering assay in detecting anti-Ro/SSA autoantibodies (the 60-kDa [Ro60] and the 52-kDa [Ro52] antibodies) and anti-La/SSB autoantibodies was evaluated. The antigens were obtained by recombinant DNA procedures to include the most immunogenic epitopes for each protein by using a prokaryotic expression system. Serum samples from 151 patients with connective tissue diseases and 52 control subjects (including patients with viral infections, patients with Lyme disease, and healthy subjects) were studied.

Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease, but specific and practicable tests for its diagnosis are lacking. We evaluated the diagnostic accuracy of a new commercial ELISA in detecting anti-cyclic citrullinated peptide (CCP) antibodies for the diagnosis of RA.

Methods: Anti-CCP antibodies were determined in 330 serum samples: 98 from RA patients and 232 from controls, including patients with connective tissue diseases, other rheumatic diseases, viral infections, Lyme disease, autoimmune thyroiditis, cancer, and monoclonal gammopathy, and sex- and age-matched healthy subjects.

[Beta-endorphin and stress hormones in patients affected by osteoarthritis undergoing thermal mud therapy].

Background: Thermal mud is a therapeutic agent widely used in the treatment of painful arthritic processes. The mechanism by which mud therapy works is still not well known. Its effect continues for months after completion of treatment.

Sensitivity and specificity of immunological methods for the detection of anti-topoisomerase I (Scl70) autoantibodies: results of a multicenter study. The Italian Society of Laboratory Medicine Study Group on the Diagnosis of Autoimmune diseases.

Background: The ability of immunometric methods to identify anti-topoisomerase I (Scl70) antibodies is controversial. We wished to quantify the performance of the currently available commercial systems for the assay of anti-topoisomerase I antibodies in a large multicenter study.

Methods: Fifty Italian clinical laboratories analyzed 36 serum samples: 27 from individuals with scleroderma/systemic sclerosis, and 9 from a control group.

Levels of C-telopeptide fragments of collagen type I enable the monitoring and early adjustment of clodronate therapy in patients with postmenopausal osteoporosis.

We monitored the efficacy of therapy with clodronate, a bisphosphonate drug, in women with postmenopausal osteoporosis, using urinary immunoenzymatic assay of C-telopeptide of collagen type I, an eight amino acid fragment (collagen fragment) of the C-telopeptide of the alpha1-chain of collagen type I (EKAHDGGR). The analysis of the dynamics of collagen fragment concentrations (a marker of bone resorption) during treatment suggests the possibility of early modulation and customization of therapy based on the levels of this marker. This could enable improved control over secondary effects and side effects of clodronate therapy.

[Cytokines of bone turnover in postmenopause and old age].

Background: The aim of the study was the assessment of the influence of cytokines on bone ageing by measuring their level in serum and their secretion in vitro by monocytes from women of different age.

Methods: The levels of cytokines in 34 postmenopausal subjects and 14 old subjects were compared to those measured in 13 cycling subjects who were considered as control group. Subjects suffering from diseases inducing secondary osteoporosis, subjects taking medications that affect bone metabolism and alcohol- or tobacco-consumers were excluded from the study.

Cd 34+ cells and clonogenicity of peripheral blood stem cells during chemotherapy treatment in association with granulocyte colony stimulating factor in osteosarcoma.

The introduction of aggressive chemotherapy in the treatment of osteosarcoma has improved the long-term outcome for these patients. With the increasing aggressiveness of chemotherapy protocols, hematopoietic growth factors have emerged as useful adjuncts involving, in some cases, rescue by peripheral blood stem cell (PBSC) infusion to assist faster recovery and maintain relative dose intensity. To evaluate the number of PBSCs needed, we analyzed the number of CD34+ cells and hematopoietic progenitor cells in the peripheral blood of 16 patients with osteoblastic, condroblastic and fibroblastic osteosarcoma enrolled in an Istituto Ortopedico Rizzoli-Scandinavian Sarcoma Group (IOR-SSG) pilot study, consisting of two cycles of preoperative high dose chemotherapy.

Evaluation of cytokines regulating bone turnover in the serum of post-menopausal and senile women.

The authors evaluated the Insulin-like Growth Factor-1 (IGF-1) stimulating the formation of bone tissue, and interferon gamma (IFN gamma), inhibiting bone resorption, in the serum of women, 13 of fertile age, 34 of post-menopausal age, and 14 of senile age. Values for IGF-1 in the serum were considerably low in patients of post-menopausal and senile age, and presented highly significant differences with values for subjects of fertile age. The values for IFN gamma did not present significant differences between different age groups.

Determination of ifosfamide by HPLC using on-line sample preparation.

The Authors have developed a novel and easily applicable HPLC method for ifosfamide (IF) determination. This method involves on-line sample processing and its solid-phase extraction by means of an automatic preparator integrated with the chromatographic system. The calibration graph of the method is linear in the concentration range 6-200 microg/ml; minimum detectable concentration is 6 microg/ml.

Variability between methods to determine ANA, anti-dsDNA and anti-ENA autoantibodies: a collaborative study with the biomedical industry.

This study was performed by the Italian Society of Laboratory Medicine (SIMeL) in order to establish the variability between the different analytical systems currently used in clinical laboratories for the detection of autoantibodies diagnostic of systemic autoimmune disease. Sixteen industrial, and two university laboratories participated in this study which entailed the determination of anti-nuclear (ANA), anti-dsDNA and anti-ENA antibodies in 11 sera from patients with clinically diagnosed systemic rheumatic disease, using reagents produced by these companies and different methodologies (indirect immunofluorescence, immunoenzymatic assay, counterimmunolectrophoresis, immuno and western blotting). We found 93.

[Seveso: biological monitoring of dioxin pollution. An example of environmental medicine. Multicentric and interdisciplinary applied research].

In 1976 the population of an area including Seveso (about 30,000) affected by the fallout of a toxic cloud containing 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) started a health monitoring plan which lasted until 1985. Smaller groups were monitored until 1997. The large number of people and the different toxic effects on organs have gathered different discipline experts including informatic.