ABSTRACT
INTRODUCTION: We evaluated analytical and clinical performances of IgG and IgM anticardiolipin (aCL) antibodies and anti-ß2-glycoprotein I (a-ß2GpI) antibodies and upper limit reference ranges (99th percentiles) in comparison with manufacturer's cutoff values with different commercial methods. METHODS: We assayed aCL and a-ß2GpI in serum samples from 30 healthy individuals, 77 patients with antiphospholipid syndrome (APS) diagnosed according to the Sydney criteria, 51 patients with autoimmune diseases, eight patients with previous thrombotic events, six patients with other diseases, and 18 patients with infectious diseases, using ELISA Inova Diagnostics; EliA Phadia Laboratory Systems; CliA Zenit-RA; and CliA Bio-Flash. RESULTS: Anticardiolipin and a-ß2GpI IgG and IgM immunoassays showed good analytic performances with both 99th percentile and manufacturer's cutoff reference values. Our results showed fair to moderate agreement among assays. In-house cutoff values gave significantly better performances only for a-ß2GpI IgG with all the immunoassays analyzed with the exception of Inova CliA Bio-Flash where we obtained the same performances with in-house and manufacturer's cutoffs. CONCLUSIONS: By guidelines, all laboratories are strongly advised to validate/verify the manufacturer's cutoff values. We recommend establishing low-positive, medium-/high-positive, and high-positive CliA IgG aCL and a-ß2GpI ranges in order to help clinicians in the diagnosis and treatment of APS.
Subject(s)
Antibodies, Antiphospholipid/blood , Immunoassay/methods , Adult , Aged , Aged, 80 and over , Antibodies, Anticardiolipin/blood , Antibodies, Antiphospholipid/immunology , Female , Humans , Immunoassay/standards , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin M/blood , Immunoglobulin M/immunology , Lupus Coagulation Inhibitor/blood , Lupus Coagulation Inhibitor/immunology , Male , Middle Aged , Reagent Kits, Diagnostic , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Young Adult , beta 2-Glycoprotein I/immunologySubject(s)
Amino Acid Substitution/genetics , Antiphospholipid Syndrome/etiology , Antiphospholipid Syndrome/genetics , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/genetics , Adult , Alleles , Contraceptives, Oral/toxicity , Female , Genetic Variation , Homozygote , Humans , Pedigree , Prothrombin/genetics , Risk Factors , Venous Thrombosis/etiologyABSTRACT
The pathophysiology and clinical severity of beta-thalassemia are related to the degree of alpha/non-alpha-chain imbalance. A triplicated alpha-globin gene locus can exacerbate effects of excess alpha-chains caused by a defective beta-globin gene, although this is not observed in all cases. Extensive studies on this condition are lacking. We report a group of 17 patients who are heterozygous for both the alpha alpha alpha(anti-3.7) allele and a mutation in the beta-globin gene cluster. Their clinical phenotypes varied: six had mild anemia with microcytosis and hypochromia, while 11 had more severe anemia with splenomegaly requiring splenectomy (three cases) and blood transfusions (four cases). Different phenotypes were also evident in the presence of the same beta-thalassemia mutation: in one family, two individuals had the same alpha- and beta-globin genotypes but presented with different hematologic phenotypes. In addition, the complex interaction involving a triplicated alpha-globin gene, beta39- and delta+27-thalassemia mutations is studied in a family with two siblings presenting with hemolytic anemia, normal Hb A2 and increased Hb F. Analysis of this series of patients suggests that additional genetic determinants play a role in modulating phenotypic expression in individuals with identical alpha- and beta-globin genotypes. Interaction with a triplicated alpha-gene can play a role in the clinical presentation of patients with defective beta-globin gene expression and should be considered in the diagnosis of atypical cases.
Subject(s)
Globins/genetics , Hemoglobinopathies/genetics , beta-Thalassemia/physiopathology , Adult , Female , Gene Expression Regulation , Heterozygote , Humans , Male , Multigene Family , Pedigree , Phenotype , beta-Thalassemia/geneticsABSTRACT
Microcytosis is a common hematological finding, usually related to iron deficiency or beta-thalassemia. When both of these conditions are excluded, alpha-thalassemia must be considered in the differential diagnosis. No simple biochemical test is able to diagnose the alpha-thalassemia trait. Using PCR amplification of the breakpoint in deletional forms, and amplification of the alpha 2 gene and restriction enzyme digestion in non-deletional forms, we identified the alpha-thalassemia carrier status in 42 out of 51 (82%) patients with microcytosis or slight microcytic anemia, unrelated to iron deficiency or beta-thalassemia. Our results underline the usefulness of molecular tests in clinical practice.
Subject(s)
Anemia, Iron-Deficiency/diagnosis , alpha-Thalassemia/diagnosis , Anemia, Iron-Deficiency/complications , Anemia, Iron-Deficiency/genetics , Female , Genotype , Humans , Male , Polymerase Chain Reaction , alpha-Thalassemia/complications , alpha-Thalassemia/geneticsSubject(s)
alpha-Thalassemia/genetics , Blotting, Southern , Chromosome Mapping , Gene Deletion , Humans , Oligonucleotide Probes , SyndromeABSTRACT
We report a patient with agnogenic myeloid metaplasia associated with debilitating bone pain due to increased bone turnover and osteosclerosis. Treatment with etidronate at a dose of 6 mg/kg per day on alternate months resulted in a complete recovery of bone symptoms and normalization of metabolic parameters of bone turnover; unexpectedly, a sustained haematological improvement was also observed after several months of therapy, suggesting that bone marrow microenvironment improvement was able to restore a nearly normal haemopoiesis. We suggest that diphosphonate therapy may be of value in patients with AMM and increased bone turnover.
