Antinuclear autoantibodies

Type III (immune complex related disease) reactions have been demonstrated by the presence of proteinuria and immune complex deposits in the kidneys of the Brown-Norway, Lewis, and PVG/C rat strains. However, susceptibility to the deposition and the subsequent lesions (glomerulamephritis) are often variable and dependent on the strain (Bigazzi, 1985). For example, despite the appearance of clinical signs and proteinuria, after two-months administration of mercuric chloride, detectable levels of circulating antinuclear autoantibodies can no longer be observed in the Brown-Norway strain (Bellon et al., 1982). By contrast, in PVG/C rats administered mercuric chloride, immune complex deposition and antinuclear autoantibodies are present for longer periods of time however, proteinurea is not observed (Weeping et al., 1978). 

A different type of immunoliposome was developed using antinuclear autoantibodies with nucleosome (NS)-restricted specificity [187], Anti-NS mAb 2C5 specifically recognizes human brain tumor cells. Evaluation of immunoliposomes 2C5-PEG-PC/Chol was carried out in nude mice bearing subcutaneous brain tumor (U-87 astrocytoma) and exhibited a threefold higher accumulation in the tumor in comparison to control (IgG-PEG liposomes). 

Chaldlam AR, Pabba S, Mongayt D, lakoubov LZ, Torchilin VP (2004) A single monoclonal antinuclear autoantibody with nucleosome-restricted specificity inhibits growth of diverse human tumors in nude mice. Cancer Ther 2 353-364... 

A number of studies have been performed to induce systemic immunosensitization and autoimmunity (i.e. autoantibody formation or autoreactive T cells) in mice, and, again, occurrence of disease appears to be strain dependent. Robinson et al. (1986) compared in one study a large number of MHC-defined mouse strains with respect to induction of antinuclear autoantibodies by mercury(II) chloride (subcutaneously, detected after 0.5-2 months), gold salts (intramuscularly, detected after 1-5 months), and D-penicillamine (orally, detected after 4.5-5 months) and reported that A.SW mice were high responders to all three chemicals. 

Antide stmcture 1408 Antiepileptic dmgs 58 Antigen-nanoparticle conjugate 1310 Antigen-presenting cell 191, 360 Antihemolytic factor Vlll, see fVlll Antihemophilia agents 454 Antinuclear autoantibodies, mononuclear 1371 Antiperinuclear factor 1192 Antisense RNA... 

Monestier, M., Novick, K.E., and Losman, M.J., D-penicillamine- and quinidine-induced antinuclear antibodies in A.SW (H-2s) mice Similarities with autoantibodies in spontaneous and heavy metal-induced autoimmunity. Eur. J. Immunol., 24, 723, 1994. 

The most common adverse reaction to etanercept is mild to moderate erythema, pain, or pruritus at the injection site (37%). Headaches and abdominal pain can also occur. New positive autoantibodies, such as antinuclear antibodies (ANA), anti-dsDNA antibodies, and anticardiolipin antibodies, can develop in patients treated with etanercept. Although there is so far no association between this and the development of autoimmune diseases or malignancies, long-term studies have yet to be done. Rare cases of pancytopenia may be associated with this drug. Although clinical trials showed no increased risk of infection with etanercept treatment, postmarketing reports of serious infections, sepsis, and associated fatalities exist. 

Injection site reactions characterized by mUd to moderate erythema, itching, burning, and/or pain occur in approximately one-third of patients but rarely necessitate drug discontinuation. The impact of etanercept on the host s response to new or chronic infections is not fully understood. Serious infections and sepsis, including fatalities, have been reported in patients treated with etanercept. Increased levels of autoantibodies, including antinuclear antibodies and anti-double-stranded DNA antibodies, have also been reported, but the clinical significance of this observation is unknown. 

Direct evidence that apoptotic cells can induce autoimmunity comes from experiments in which normal mice injected with syngeneic apoptotic thymocytes developed antinuclear, anticardiolipin, and anti-ssDNA antibodies. These mice suffered from immunoglobulin G deposition in the glomeruli several months after immunization (M16). How do apoptotic cells induce production of autoantibodies ... 

Activated partial thromboplastin time, anticardiolipin antibody,° antinuclear and other autoantibodies... 

Evidently, ANA (first described by G.J. Friou et al. in 1957) belong to the natural autoantibodies which are continuously stimulated by a still unknown mechanism (possibly a persisting agent) in certain diseases. However, this antibody phenomenon is inconsistent and neither organ- nor disease-specific. ANA can be visualized by immunofluorescence in cryostat tissue sections of the rat liver and rat kidney as a homogeneous (s. fig. 5.10), speckled (s. fig. 5.11), circular or nuclear fluorescence pattern. This allows conclusions to be drawn as to the specificity of antinuclear antibodies and in some cases as to the nature of the underlying disease as well. 

Treatment with sulfasalazine was associated with lupus-Uke symptoms and systemic lupus eiythematosus-related autoantibody production in 10% of patients with early rheumatoid arthritis risk factors included a systemic lupus eiythematosus-related HLA haplotype, increased serum interleukin-10 concentrations, and a speckled pattern of antinuclear antibodies (96). 

Although patients treated with etanercept commonly develop new antinuclear antibodies or anti-double-stranded DNA antibodies, there were no reports of cutaneous or systemic lupus erythematosus in early clinical trials. However, since then, at least eight cases have been reported, including five patients with a lupus-like syndrome, two with acute discoid lupus, and one with subacute cutaneous lupus erythematosus (26-29). All were women and they developed their first symptoms 6 weeks to 14 months after the first injection of etanercept. Antinuclear and/or anti-DNA antibodies were positive in most of them. Etanercept was withdrawn in all patients with features of systemic lupus erythematosus, and the symptoms resolved within 2-8 weeks. The skin lesions also improved with local glucocorticoids, despite continued etanercept treatment in two patients with discoid lupus or subacute cutaneous lupus erythematosus. This suggests that etanercept-induced autoantibodies are sometimes associated with clinical autoimmune disease. 

After taking sodium aurothiomalate for 10 months (cumulative dose 550 mg) a 12-year-old girl with severe exudative polyarthritis developed pericarditis, high titers of antinuclear antibodies, and antibodies to native double-stranded DNA (70). After withdrawal her sjmiptoms rapidly disappeared and did not recur after a follow-up period of 5 years. The titers of autoantibodies fell to normal within 1 year. 

Collectively, several antibodies (mostly antinuclear, antithyroid, parietal cell, liver/kidney microsome, and smooth muscle antibodies, and rheumatoid factor) can be detected before interferon alfa treatment in about one-third of patients. Increased titers or the occurrence of various autoantibodies were observed in 4-30% of previously autoantibody-negative patients (21,156). These autoantibodies do not affect the response to... 

Seven patients (17-22 years old) developed sjmptoms of arthralgia and arthritis after having taken minocycline 50-100 mg bd for 6-36 months for acne vulgaris (47). Increased titers of perinuclear ANCA were detected in all seven, five had fluorescent antinuclear antibodies, two had antihistone autoantibodies, and one had anticardiohpin antibodies. Symptoms resolved in five patients on withdrawal the other two were treated with corticosteroids and also achieved remissions. 

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). 

Nancey S, Blanvillain E, Parmentier B, Flourie B, Bayet C, Bienvenu J, Fabien N Infliximab treatment does not induce organ-specific or nonorgan-specific autoantibodies other than antinuclear and anti-double-stranded DNA autoantibodies in Crohn s disease, Inflamm Bowel Dis 2005,11 986-991... 

Based on experimental studies it has been suggested that sihcates may stimulate lymphocytes via a T-cell receptor Vp-specific T-cell activation pathway resulting in the production of autoantibodies or autoimmune diseases [94, 98, 99]. In this context it must be noted that not only ANCA s but also other autoantibodies such as antinuclear antibodies and rheumatoid factors frequently occur in workers heavily exposed to silicon-containing compounds [68, 77]. 

Parietal cell, thyroid, and antinuclear antibodies have been reported to be increased in lithium-treated patients (145-147). Autoantibodies directed at pituitary functions have also been demonstrated in lithium-treated patients and this may reflect modulation by lithium of pituitary and hypothalamic centers (148, 149). Tissue-specific autoantibodies such as these may or may not be related to autoimmune disease lithium may, in any case, modulate preexisting autoimmune processes rather than induce them (150). 

AIH is associated with the presence of liver- and nonliver-related autoantibodies m plasma. These are helpful in diagnosis, but are not likely to be the cause of liver injury. The most important antibodies for diagnosis include antinuclear antibody (ANA), antismooth muscle antibody (ASMA), and antiliver-kidney microsomal antigen type 1 (LKMi). A variety of other autoantibodies are found frequently in AIH, some of which are found in other disorders. A summary of the most common autoantibodies, their associations, and their molecular targets (when known) is given... 

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