Lupus, autoimmune-induced

Many skin disorders are associated with at least one of the characteristics of inflammation, oxidative stress, hyperproliferation, hypodifferentiation, infection, apoptosis, and autoimmune reactions. GTPs are uniquely positioned to antagonize these conditions with anti-inflammatory, antioxidant, antimicrobial, prodifferentiation, anti-apoptosis, and inhibition of autoantigen properties. Thus, many skin conditions, including autoimmune-induced lupus and psoriasis, wounds created by trauma or infections, damage induced by environmental factors such as UVB, and seborrheic dermatitis (dandruff), could be treated or managed by topical application of GTPs. 

Minocycline is associated with a relatively high incidence of hepatotoxicity. In many cases it is quite distinct from minocycline-induced lupus, occurs earlier in the course of treatment (about 1 month), and the mechanism is unknown [62], However, in some cases the liver toxicity merges with the lupus-like syndrome, occurring after about a year of therapy, and is associated with ANA. This form is indistinguishable from idiopathic autoimmune hepatitis [63], and antibodies against Cyp 3A6 and Cyp 2C4 have been reported [64], Diclofenac has also been reported to cause hepatitis with autoimmune features such as ANA [65],... 

An important animal model of lupus is the lpr mouse. It was discovered that the abnormality leading to autoimmunity in this model is a defect in the gene coding for Fas protein and this leads to impaired apoptosis [103], This, in turn, leads to lymphade-nopathy and prevents elimination of autoimmune T cells, thus interfering with tolerance. Minocycline inhibits apoptosis, and it has been postulated that this contributes to the mechanism of minocycline-induced lupus [104],... 

Kretz-Rommel, A., Duncan, S.R., and Rubin, R.L., Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus, J. Clin. Invest., 99,1888, 1997. 

The dog is a species that is frequently used in toxicity studies. However, there are few reports in the open literature on dog studies with respect to chemical- or drug-induced hypersensitivity reactions or autoimmune effects, and those that are available lack consistency. For instance, procainamide has been shown to induce lupus-like symptoms (mainly an increase of ANA) in one study [63], but not in another study with younger dogs [64], Similar discrepancies have been observed for hydralazine-induced effects in dogs [5],... 

Aucoin, D.P. Propylthiouriacil-induced immune mediated disease syndrome in The cat A novel model for a drug-induced lupus-like disease, in Autoimmunity and toxicology. Immune disregulation induced by drugs and chemicals. Kammuller, M.E., Bloksma, N. and Seinen, W., eds., Elsevier, Amsterdam, 1989, chap. 12. 

This case is the first report of drug-induced lupus-like syndrome concomitant with severe autoimmune hepatitis in a genetically predisposed patient (23). 

Graziadei IW. Drug-induced lupus-like syndrome associated with severe autoimmune hepatitis. Lupus 2003 12 409-12. 

Sarzi-Puttini P, Atzeni E, Capsoni F, et al. Drug-induced lupus erythematosus. Autoimmunity 2005 38 507-518. 

Yung RL, Quddus J,ChrispCE, Johnson KJ, Richardson BC Mechanisms of drug-induced lupus I. ClonesTh2 cells modified with DNA methylation inhibitors n vitro cause autoimmunity in vivoJ. Immunol. 1995 154 3025-3035. 

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. 

Sarzi-Puttini P, Atzeni F,Capsoni F, Fubrano E, Doria A Drug-induced lupus erythematosus, Autoimmunity 2005,38 507-518 Vielhauer V, Mayadas TN Functions of TNF and its receptors in renal disease distinct roles in inflammatory tissue injury and immune regulation, Semin Nephrol 2007,27 286-308... 

Rowley Monestier (2005) reviewed mechanisms of the induction of autoimmunity by the heavy metal mercury in the rat and mouse. In contrast to the rat autoimmune model, in the mouse model for autoimmunity induced by mercury, the autoantibody response is specifically targeted towards nucleolar antigens and is associated with induction of antifibrillarin autoantibodies. Second, exposure to low doses of mercury can dramatically worsen the development of autoimmune responses in lupus mouse models. A third difference is the nature of the interaction of heavy metals such as mercury with thiol groups and the role of this affinity in the availability of certain thiol-containing molecules for immature cells. 

Procainamide, widely used in the treatment of ventricular and supraventricular arrhythmias in the past, recently had its use restricted to short-term treatments due to the induction of autoimmunity and the development of drug-induced lupus (Ayer et al., 1993 Kretz-Rommel Rubin, 1999). It has been suggested that procainamide-induced autoimmunity is characterized predominantly by an antihistone and anti-denatured DNA immune response (Rubin et al., 1986 Rubin, 1992 Mongey Hess, 2001). Mechanistic studies have revealed that procainamide is a competitive DNMT inhibitor of some, but not all, nuclear methyltransferase activity (Scheinbart et al., 1991 Richardson, 2003). 

Kuroda et al. (2004) reported autoimmunity induced by adjuvant hydrocarbon oil components of some human and veterinary vaccines. This study showed that an injection of certain adjuvant hydrocarbon oils (pristane, incomplete Freund s adjuvant, or squa-lene) induced lupus-related autoantibodies to nuclear ribonucleo-proteins (nRNP)/Sm and Su in non-immune Balb/c mice. 

Aucoin DP (1989) Propylthiouracil-induced immune mediated disease syndrome in the cat a novel model fora drug-induced lupus-like disease. In Kammuller ME, Bloksma N, Seinen W eds. Autoimmunity and toxicology immune disregulation induced by drugs and chemicals. Amsterdam, Elsevier, pp 309-320. 

Other adverse effects are caused by immunological reactions, of which the drug-induced lupus syndrome is the most common. Hydralazine also can result in an illness that resembles serum sickness, hemolytic anemia, vasculitis, and rapidly progressive glomerulonephritis the mechanism of these autoimmune reactions is unknown. The drug-induced lupus syndrome usually occurs after at least 6 months of continuous treatment with hydralazine, and its incidence is related to dose, sex,... 

Odobasic, D., Muljadi, R. C., O Sullivan, K. M., etal. (2015). Suppression of autoimmunity and renal disease in pristane-induced lupus by myeloperoxidase. Arthritis and Rheumatism, 67(7), 1868-1880. 

Katz U, Zandman-Goddard G. Drug-induced lupus an update. Autoimmun Rev 2010 10(1) 46-50. 

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