ABSTRACT
Drug development is a lengthy, costly, and complex process, with clinical trials essential for characterizing dosing, safety, and efficacy in treated populations. After regulatory approval, aggressive marketing ensures that most drugs are used by a broad spectrum of ages, genders, races, and ethnic groups. Unfortunately, not all groups are adequately represented in clinical trials; adolescents are commonly overlooked. This commentary explores how adolescents are considered during drug development, with a special focus on the influence of inherent psychosocial, biological, ethical, and regulatory issues in their recruitment and participation in clinical studies leading to drug licensing.
Subject(s)
Adolescent Medicine , Clinical Trials as Topic , Pharmaceutical Preparations/administration & dosage , Pharmacology, Clinical/standards , Adolescent , Age Factors , Drug Approval , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Male , Needs Assessment , Patient Selection , Pharmacology, Clinical/trends , Psychology , Risk Assessment , United StatesABSTRACT
We describe the first case in which de novo production of multiple IgG antinuclear antibodies (ANA) occurred in a female neonate of an ANA negative mother. The infant presented at 4 weeks of age with hemorrhagic panencephalitis, diffuse intraparenchymal hemorrhages, and straight sinus thrombosis. She had been vaccinated against hepatitis B at birth. No other cause was found and maternal prenatal care was unremarkable. The infant's screening ANA test by ELISA was positive at 6 weeks with specificity for ssDNA, Sm, and nRNP/Sm. At 8 weeks antibodies to dsDNA and centromere were detected as well. By 8 months, she still had slightly elevated anti-dsDNA, Sm, and nRNP/Sm antibodies. The ANA test by immunofluorescence was abnormal at 8 weeks through 13 weeks with centromere and then homogeneous pattern. Based on similarities with other reported cases, we speculate that hepatitis B vaccination may have been involved in the development of antinuclear antibodies.
Subject(s)
Antibodies, Antinuclear/immunology , Immunoglobulin G/analysis , Ribonucleoproteins, Small Nuclear , Adult , Autoantigens/immunology , Centromere/immunology , DNA/immunology , DNA, Single-Stranded/immunology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant, Newborn , Reference Values , Sinus Thrombosis, Intracranial/complications , Sinus Thrombosis, Intracranial/immunology , Sinus Thrombosis, Intracranial/pathology , Subacute Sclerosing Panencephalitis/complications , Subacute Sclerosing Panencephalitis/immunology , Subacute Sclerosing Panencephalitis/pathology , snRNP Core ProteinsABSTRACT
Bovine antigens are routinely used in indirect ELISA tests to detect autoantibodies against extractable nuclear antigens (ENA). Here we investigate the difference in clinical sensitivity between ELISA tests prepared with native human and bovine antigens. SSA and SSB were obtained from spleen and nRNP/Sm complex from thymus. Each antigen was extracted with the same immunoaffinity column. ELISA tests with human and bovine antigens were set up under the same conditions of clinical specificity established on 50 blood bank donors. Of 109 random SLE and Sjogren's syndrome sera 49% and 35% were positive, respectively, for human and bovine SSA, 26% and 16% for SSB. Of 98 random SLE sera 52% and 41% were positive for human and bovine nRNP/Sm, respectively. A few specimens reacted only with bovine antigens, probably false positive reactions. The relative clinical sensitivity for all specimens identified as positive by human and/or bovine antigens was significantly higher with human than with bovine SSA, (93% vs 67%; P<0.001, chi2), SSB (93% vs 50%; P<0.001), and for nRNP/Sm (96% vs 75%; P<0.01). However, for values that exceeded 2.5-4 times the upper normal limit, the levels were similar for human and bovine antigens. We concluded that native human antigens offer clinical sensitivity superior to native bovine antigens for the measurement of anti-ENA antibodies by ELISA.