This information is very important in understanding lupus and ai symptoms and diseases and why certain ones cluster together. I think this info will ultimately lead to many effective treatments and prevention. Testing for these agents and the development of anti-interferons and anti-tnf and anti-il2 (anticytokines) are already being developed and in some cases, you are on one. This article discusses cytokines and I personally believe that some of us just naturally have higher levels of some rather than others and if this could be detected early, disease could be prevented. People with high levels of certain cytokines may or may not develop anti ds-dna but can still have a form of autoimmune disease, though harder to pinpoint. In these cases, people were given cytokines for treatment of other conditions and this report tracks the changes that happened to them so docs can better know how to treat their patients.
INDUCTION OF AUTOIMMUNE PHENOMENA
Treatment with biologic agents has been associated with exacerbation and triggering of autoimmune conditions. Autoimmune phenomena may present as asymptomatic autoantibody production or overt autoimmune conditions.
TNF-α is a potent proinflammatory cytokine elaborated by mononuclear cells (19). It increases secretion of other pro-inflammatory mediators, induces expression of cell adhesion molecules, and stimulates production of proteolytic enzymes (20). TNF-α has been shown to play an important role in the pathogenesis of several inflammatory and autoimmune diseases. ...
Interferons play an important role in host resistance to viral infections acting through different mechanisms such as stimulation of natural killer (NK) cell activity and T-cell mediated immunity, cytokine synthesis, and activation of macrophages (53). Interferons were used to treat persistent viral infections such as hepatitis B and C (54,55) and several hematologic and solid malignancies such as hairy cell leukemia, chronic myeloid leukemia (CML), multiple myeloma and indolent lymphoma (56-59), carcinoid tumors, and breast cancer (60,61)....
Autoimmune phenomena have been recorded frequently following treatment with IFN-α. The most common autoimmune side effect seems to be the appearance of anti-thyroid antibodies and clinically overt and sometimes permanent thyroid disease (62). ...
IFN-β, used in the in treatment of multiple sclerosis (MS), binds to type I interferon receptor, and exerts anti-viral, anti-tumor, and anti-inflammatory activity.
IFN-g is produced by NK cells and binds to type II interferon receptor. It is less effective than IFN-α at inducing NK cells and has less potent anti-viral and anti-tumor activities. However, IFN-g is the most potent inducer of macrophage activation and MHC class II molecules (110). IFN-g stimulates immunoglobulin secretion by B cells and promotes T-cell differentiation towards Th1 type....
IFN-g has been reported to be effective in preventing serious infections in patients with chronic granulomatous disease. It has been also used as an adjuvant with the antimicrobial treatment of intracellular infections such as Leprosy (111). Efficacy of IFN-g has also been evaluated in patients with RA, based on the observations of low levels of IFN-g in the RA environment. Yet, a multi-center, double-blind, placebo-controlled study showed no therapeutic benefit of IFN-g over placebo (112). ......
Seitz et al (114) reported induction of ANA in 2 of 6 RA patients treated with IFN-g. In this study, high dose of IFN-g was used as compared with other surveys. The titers of ANA decreased on reduction of dosage. Two reports of life-threatening SLE during IFN-g therapy were published (115,116). Three additional patients who were treated with combination of IFN-g and IFN-α for myeloproliferative disorders developed SLE. IFN-g was shown to play a role in the pathogenesis of SLE in animal models. Administration of IFN-g accelerates the rate of progression to glomerulonephritis in lupus-prone (NZBXNZW)F1 mice and is prevented by treatment with anti-IFN-g antibodies (117). Transgenic mice that over-express IFN-g in the epidermis produce antibodies to dsDNA (118). Elevated serum levels of IFN-g were reported in patients with SLE (119). On the other hand, IFN-g has been shown to play an important role in inducing CTL activity and preventing lupus-like disease in an animal model of GVHD (42). IFN-g has complex and seemingly contradictory actions as immunostimulator and immunosuppressor depending on the type and the stage of immune response. ...
Therapeutic use of various cytokines is constantly expanding. Side effects of cytokine therapy may include triggering and exacerbation of immune and autoimmune conditions, which may evolve into overt autoimmune disorders. Although uncommon, these disorders may be life threatening. Autoimmune manifestations associated with cytokine therapy seem to be more common in the patients with pre-existing tendency to autoimmunity. Clinicians should be aware of potential autoimmune adverse effects of cytokine therapy, and patients who are prone to develop these side effects should be detected. Although it is not clear whether all patients treated with cytokines should be routinely screened for the presence of autoantibodies, clinical follow-up regarding signs and symptoms of autoimmune disorders is recommended. Further studies are needed to clarify the mechanisms involved in development of autoimmune phenomena that occur in the course of cytokine therapies.
Table 1: Autoimmune manifestations of anti-TNF-α therapyAutoantibodiesANA (28)Anti-dsDNA (22,28)Anti-chromatin (28)Anti-histone (30)Anti-Sm (30)Anti-RNP (30)Anti-cardiolipin (43)Clinical manifestationsSLE (28,30,31)Demyelinating disorders (44)Discoid lupus (48)Necrotizing vasculitis (49)Accelerated nodulosis (50)Bullous skin lesions (51))Nephrotic syndrome (52)
Table 2: Autoimmune manifestations associated with IFN-α therapyAutoantibodies Anti-thyroid antibody (62-65)ANA (60)Anti-dsDNA antibody (66)Anti-parietal cell antibody (62)Clinical manifestationsSLE (64,65,67-70)Polyarthropathies (72)Seronegative arthropathies (73-76)Thrombocytopenia (77)Haemolytic anemia (65)Insulin dependent diabetes mellitus (78,79)Vasculitis (80)Vasculitic neuropathy (86)Psoriasis (81)Hemophilia (82)Thrombotic microangiopathy (83-85)Membranous glomerulonephritis (65)Autoimmune hepatitis (64)Vitiligo (63,65)Polymyositis (65,66)
Table 3: Autoimmune manifestations associated with IL-2 therapyThyroid dysfunction (122,123)Arthritis (126,127)Myositis (127,128)Systemic sclerosis (129)Pemphigus vulgaris (132)Vitiligo (133)Carpal tunnel syndrome (134)