Autoantibodies drug-induced

Layland, L.E. et al., Drug-induced autoantibody formation in mice Triggering by primed CD4+ CD25 T cells, prevention by primed CD4+ CD25+ T cells, Eur. J. Immunol., 34,36,2004. 

Beaune P, Dansette PM, Mansuy D, Kiffel L, Einck M, Amar C et al. Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Proc Natl Acad Sci USA 1987 84 551-5. 

Cholestatic hepatitis occurred in an 83-year-old man after 9 months of continuous therapy with moxonidine. No autoantibodies were detected and liver biopsy showed features compatible with drug-induced inflammatory intrahepatic cholestasis. The patient recovered fully and his biochemical data normalized 8 weeks after withdrawal. 

Korman NJ, Eyre RW, Zone J, Stanley JR. Drug-induced pemphigus autoantibodies directed against the pemphigus antigen complexes are present in penicillamine and capto-prU-induced pemphigus. J Invest Dermatol 1991 96(2) 273-6. 

Thymus function in 10 patients with sjmiptomatic procainamide-induced lupus has been compared with that in 13 asymptomatic patients who only developed drug-induced autoantibodies (45). Newly generated T cells were detected in all the subjects. Although there was no overall quantitative difference between the sjmp-tomatic and asymptomatic patients, there was a correlation between the level of T cell receptor rearrangement excision circles in peripheral lymphocytes and serum IgG antichromatin antibody activity in patients with drug-induced lupus. These results support the hypothesis that the thymus is important in the genesis of drug-induced lupus-like syndrome and that the production of autoreac-tive T cells starts in the thymus when procainamide hydroxylamine alters T cell tolerance. 

The antinuclear antibody is positive in virtually all cases and the ESR is often raised. Antihistone antibodies are also present in most cases. The prevalence of serum autoantibodies to high-mobility group (HMG) proteins in the serum of patients with drug-induced lupus-like syndrome varies from protein to protein 67% for HMG-14 and/or HMG-17 compared with 21% for HMG-1 and/or HMG-2. Procainamide-induced lupus is also associated with antibodies to the H2A-H2B dimer (55,56). 

Burlingame RW, Rubin RL. Drug-induced anti-histone autoantibodies display two patterns of reactivity with substructures of chromatin. J Chn Invest 1991 88(2) 680-90. 

Despite a good overall safety profile, anti-TNF antibodies can induce a number of adverse effects, including autoimmunity and infections. A trial in the treatment of Crohn s disease noted infusion reactions, transient increased of anti-dsDNA antibodies, and serum sickness-like delayed hypersensitivity with retreatment. Induction of human-antichimeric-antibodies was suggested as the cause of some of the infusion reactions [90]. A prospective study in 35 patients with Crohn s disease showed induction of ANA and anti-dsDNA autoantibodies in 53% and 35% of infliximab-treated patients [91]. A single patient showed clinical features consistent with drug-induced lupus, including the presence of ANA and anti-dsDNA autoantibodies, which quickly resolved after discontinuation of infliximab. Reports on renal adverse effects of anti-TNF antibodies are very rare. Saint Marcoux described the occurrence of crescentic GN in as few as 2 patients out of a cohort of 39 patients, treated with an anti-TNF antibody for rheumatoid arthritis [92]. A case report by Chin et al. [93] described the case of a 29-year-old Australia-born Vietnamese who presented with nephrotic syndrome. A renal biopsy showed membranous nephropathy. Symptoms attenuated after discontinuation of infliximab therapy. 

Beane PH, Bourdi M. Autoantibodies against cytochrome P450 in drug-induced autoimmune hepatitis. Ann NY Acad Sci 1993 685 641-645. 

Autoimmune haemolytic anaemia (AIHA). Acquired haemolytic anaemia mediated by autoantibodies against antigens on the organism s own red cell membrane. Autoimmune haemolytic anaemia may be idiopathic, secondary to lymphoproliferative, autoimmune (e.g. systemic lupus erythematosus), or chronic inflammatory disorders, postinfectious or drug-induced. See also -anaemia, cold autoantibody type, warm autoantibody type, -drug-induced immune haemolytic anaemia. 

Rubin RL (1992) Autoantibody specificity in drug-induced lupus and neutrophil-mediated metabolism of lupus-inducing drugs. Clin Biochem, 25(3) 223-234. 

LeCluyse EL, Alexandre E, Hamilton GA, Viollon-Abadie C, Coon DJ, Jolley S, Richert L (2005) Isolation and culture of primary human hepatocytes. Methods Mol Biol 290 207-229 Lecoeur S, Andre C, Beaune PH (1996) Tienilic acid-induced autoimmune hepatitis anti-liver and-kidney microsomal type 2 autoantibodies recognize a three-site conformational epitope on cytochrome P4502C9. Mol Pharmacol 50 326-333 Lee WM (2003) Drug-induced hepatotoxicity. N Engl J Med 349 474-485 Lee WM, Senior JR (2005) Recognizing drug-induced liver injury ctnrent problems, possible solutions. Toxicol Pathol 33 155-164... 

Drug-induced autoantibodies behave serologically like those seen in patients with autoimmune hemolytic disease not associated with drug exposure. Red cell eluates often react preferentially with certain antigens of the Rh system (Salama et al. 1991). Unfortunately, there is no way to confirm that a pharmacologic agent was the trigger for the autoantibody in a particular patient. 

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