Autoantibody production

Mizoguchi, A., Mizoguchi, E., Chiba, C., Spiekermann, G.M., Tonegawa, S., Nagler-Anderson, C. and Bhan, A.K. (1996) Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease. Journal of Experimental Medicine 183, 847-856. 

D. Etanercept is a recombinant fusion protein consisting of two TNF receptor domains linked to one IgG Fc molecule. It binds to soluble TNF-a and TNF-(3 and forms inactive complexes. It does not directly affect cAMP phosphodiesterase, leukotriene synthesis, or autoantibody production. 

The autoantibody production in autoimmune diseases may be attributed to the inability of Treg cells to control their synthesis. In an autoimmune model, T cells regulate the mechanisms through which B cells that were autoreactive to selfantigens do not produce autoantibodies, suggesting a role for suppressor T cells. The administration of irradiation, thymocytes, lymph nodes or spleen cells inhibits the production of autoantibodies, which is attributed to the suppressor T cells. 

SLE is the prototype systemic autoimmune disease, with a hallmark of autoantibody production. The mechanism leading to loss of self-tolerance and production of autoantibodies is discussed in Section 2. 

Just as with murine models, knowledge of the genetics of human lupus also provides hints concerning the mechanism of autoantibody production in SLE. This will be discussed in Section 2. 

Direct evidence of DNA as an antigen source to drive autoantibody production was derived from experiments using combined DNA-protein as an immunogen to immunize mice. The mice immunized with the DNA-peptide complex produce anti-dsDNA antibodies with pathogenic properties (D7). 

Mechanism of ANTi-dsDNA, Anti-Ro/SSA, and ANTi-La/SSB Autoantibody Production in Patients with SLE... 

C4. Casciola-Rosen, L., and Rosen, A., Ultraviolet light-induced keratinocyte apoptosis A potential mechanism for the induction of skin lesions and autoantibody production in LE. Lupus 6, 175—... 

Wardemann, H., S. Yurasov, A. Schaefer, J. W. Young, E. Meffre, and M. C. Nussenzweig. 2003. Predominant autoantibody production by early human B cell precursors. Science 301 1374-1377. 

Serum IL-6 levels are usually very low or not measurable prior to middle age. However, subsequent IL-6 dysregulation results in increased production such that it is readily measurable in older persons even in the absence of inflammation. It has been suggested that dysregulation of IL-6 gene expression may be related to increased autoantibody production and the presence of benign paraproteinemia, both of which are commonly present in the elderly (Rl). Moreover, increased IL-6 levels may be responsible for the age-associated development of malignant B-cell tumors. In addition, Ershler (E4) noted that increased IL-6 has been associated with alteration of amyloid precursor protein, as is present in Alzheimer s disease, and stimulation of postmenopausal bone resorption. IL-6 has also been implicated in multiple myeloma, lymphoma, rheumatoid arthritis, Castleman s disease, and cardiac myxoma (E4). 

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 infliximab has been associated with autoantibody production, it is not known whether it contributed to hypercoagulability in this patient. 

Bagenstose, L.M., P. Salgame and M. Monesteir. IL-12 down-regulates autoantibody production in mercury-induced autoimmunity. J. Immunol. 160 1612-1617, 1998. 

The etiology of abnormal autoantibody production and development of SLE is still unknown. Genetic, environmental, and hormonal factors all may play arole in loss of self tolerance and expression of disease. A popular theory is that autoimmune disease such as SLE develops in genetically susceptible individuals after exposure to a triggering agent, possibly something in the environment. ... 

Garratty G, Arndt P, Prince HE, Schtilman lA. The effect of methyldopa and procainamide on suppressor cell autoantibody production. Br J Haematol 1993 84 310. 

Peng SL, Szabo SJ, Glimcher LH. T-bet regulates IgG class switching and pathogenic autoantibody production. Proc Natl Acad Sci USA. 2002 99 5545-5550. 

The heterogeneity of most of the systemic but also organ-specific autoimmune diseases is an additional important factor that complicates genetic analyses. Careful disease classification is necessary, and differentiation of subgroups according to clinical presentation, autoantibody production, ethnic background, as well as environmental exposures may be helpful. The risk associated with one genetic risk factor for an autoimmune disease may be... 

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