Procainamide‐induced serologic changes in asymptomatic patients

Molina, Javier; Dubois, Edmund L.; BILITCH, MICHAEL; Bland, Stephen L.; Friou, George J.

doi:10.1002/art.1780120608

Cited by 49 publications

(8 citation statements)

References 15 publications

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“…The production of various autoantibodies indicative of a state of autoimmunity has been observed commonly in patients treated with procainamide (PA)' for cardiac arrhythmia (1)(2)(3)(4)(5)(6). Prospective studies have revealed that PA may induce antinuclear antibodies in 50-83% of individuals, and that 12-29% of PA-treated patients develop a syndrome resembling systemic lupus erythematosus (SLE) (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

“…The development of autoimmunity induced by PA is influenced by factors that affect the serum level of this agent. These include dosage (2), duration of administration (8), and rate of acetylation of the parent drug (11). Thus, individuals who are slow acetylators maintain higher serum levels of PA and develop antinuclear antibodies sooner than those who are fast acetylators (11).…”

Section: Introductionmentioning

confidence: 99%

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Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro.

Ochi¹,

Goldings²,

Lipsky³

et al. 1983

J. Clin. Invest.

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A B S T R A C T Procainamide (PA) induces the production of a number of autoantibodies in a high proportion of treated individuals and in some a syndrome closely resembling systemic lupus erythematosus. The mechanism underlying this action of PA is unclear. To examine the possibility that PA might induce autoantibody formation by altering normal immunoregulatory mechanisms, the action of this drug on an in vitro model of antibody formation in man was examined. PA was found to augment the generation of immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (PBM) in response to pokeweed mitogen but had no effect on pokeweed mitogen-induced tritiated thymidine incorporation. When purified populations of B and T cells were used, PA enhanced the generation of ISC in B-cell cultures supported by untreated T cells but not by T cells treated with mitomycin C. These results indicate that PA augmented B-cell responses by inhibiting suppressor T-cell activity and not by augmenting helper T-cell or B-cell function. N-Acetyl-procainamide had no effect on the generation of ISC in this system.The effect of PA on concanavalin A (Con A)-induced suppressor cell activity was also examined to determine whether PA altered the generation or expression of suppressor T-cell function. PBM were cultured with 30 Aig/ ml of Con A for 48 h to generate suppressor cells. When these were co-cultured with fresh PBM, the number of ISC generated was decreased by 58.1±3.4% (mean ±SEM, n = 6). Cells that had been similarly incubated without Con A were not inhibitory. The addition of PA to the Con A-stimulated cultures inhibited the generation of suppressor cells as indicated by the fact that the response of fresh cells co-cultured with the Con A-stimulated cells was diminished by only 27.2±4.3%. In this system too, N-acetyl-procaimamide had no effect. By contrast, adding PA only to the co-culture of Con A-

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro.

Ochi¹,

Goldings²,

Lipsky³

et al. 1983

J. Clin. Invest.

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“…Anti-dDNA is often found (3,22), but its relationship to the clinical manifestations have not been established. Data concerning the presence of anti-nDNA are conflicting (3,13,22,27).…”

mentioning

confidence: 99%

Anti‐DNA antibody in procainmide‐induced lupus erythematosus. Determination using DNA fractionated by methylated albumin‐kieselguhr chromatography

Winfield

Davis

1974

Arthritis & Rheumatism

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Both putatively native(n) commercial calf thymus DNA and I4C labeled human KB DNA contained significant amounts of denatured DNA (dDNA) as determined by methylated albumin-kieselguhr chromatography. The proportion of dDNA in these preparations was sufficient to cause confusion regarding the antigenic specificity of anti-DNA antibody when unfractionated DNA was used in either the counterimmunoelectrophoresis or the Farr assays for anti-DNA antibody. Serum from patients with systemic lupus erythematosus contained both anti-nDNA and anti-dDNA antibodies. About 50 % of patients with symptomatic procainamide-induced lupus (PLE) exhibited anti-dDNA; none had anti-nDNA. Procainamide treated patients with a positive ANF who did not have symptomatic PLE had neither anti-dDNA nor anti-nDNA. Considerable data sumort the concept & Ithat native DNA (nDNA) and anti-nDNA antibody are of primary pathogenetic im-

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“…A Possible Explanation for Drug-induced Autoimmunity HARRY G. BLUESTEIN, DOUG REDELMAN, and NATHAN J. ZVAIFLER Procainamide therapy has been associated with a lupus erythematosus (LE) like illness. At least 50% of patients who take the drug for a long time develop antinuclear antibodies and approximately 10% of these develop the complete clinical syndrome (1)(2)(3). There has been considerable speculation about the pathogenesis of the drug-induced disease.…”

Section: Procainamide-lymphocyte Reactionsmentioning

confidence: 99%

Procainamide‐lymphocyte reactions. a possible explanation for drug‐induced autoimmunity

Bluestein

Redelman

Zvaifler

1981

Arthritis & Rheumatism

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Procainamide therapy has been associated with a lupus erythematosus (LE) like illness. At least 50% of patients who take the drug for a long time develop antinuclear antibodies and approximately 10% of these develop the complete clinical syndrome (1-3). There has been considerable speculation about the pathogenesis of the drug-induced disease. Most theories implicate drugnucleoprotein interactions, which result in the induction of antinuclear antibodies, but these explanations do not account for other autoantibodies often present in a patient with drug-induced lupus.The autoimmune phenomena of idiopathic lupus have been attributed to impaired immune regulation (4). To determine if similar mechanisms operate in the drug-induced syndrome, we looked for evidence of procainamide-induced lymphocyte abnormalities and found that many individuals taking the drug develop antibodies to cell surface antigens on normal lymphocytes. The frequency with which these antilymphocyte (ALA) antibodies develop and their concentration in the circulation are significantly increased in those patients with the procainamide-induced lupus syndrome. When the drug is discontinued, the antilymphocyte activity diminishes rapidly, in parallel with clinical improvement. We also found that procainamide alters the in vitro proliferative response of normal human lym- phocytes to mitogenic and antigenic stimulation. Taken together, these findings raise the possibility that procainamide induces the autoimmune lupus-like syndrome by its direct interaction with lymphocyte membranes. Clinical observationsSeventeen patients were identified as having procainamide-induced lupus as evidenced by a history of continued procainamide therapy, the development of new symptoms compatible with lupus, a serum antinuclear antibody titer of 1 : 10 or greater, and resolution of symptoms after discontinuation of the drug. The patients ranged in age from 49 to 83 years and 15 were male. The average total procainamide dose per patient in those with the drug-induced lupus syndrome was 695 gm, ranging from 60 to 1320.The clinical features of the procainamide-induced syndrome in our 17 patients included rheumatic complaints (arthralgia, diffuse myalgia, and arthritis) in 16; pleurisy or chest pain in 12; fever and weight loss in 7; and skin rash, mental confusion or headache, and Raynaud's phenomenon in 3 patients each. All subjects had a positive antinuclear antibody test, most with titers of 1 : 320 or greater. Serum antibodies to native doublestranded DNA (Farr technique) were not detected in any samples. Other immunologic abnormalities included positive direct and indirect Coombs tests, total leukocyte counts of less than 3000/mm3, and mild depressions in C3 or C4. A surprising finding was a circulating anticoagulant in 3 patients and an unexplained prolonged partial thromboplastin time (PTT) in another.

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Procainamide‐induced serologic changes in asymptomatic patients

Cited by 49 publications

References 15 publications

Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro.

Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro.

Anti‐DNA antibody in procainmide‐induced lupus erythematosus. Determination using DNA fractionated by methylated albumin‐kieselguhr chromatography

Procainamide‐lymphocyte reactions. a possible explanation for drug‐induced autoimmunity

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