The fully blown disease of human progressive systemic sclerosis (PSS, scleroderma) is serologically associated with the emergence of several types of autoantibodies, some of them regarded as more specific for scleroderma (e.g. Scl-70, anti-centromere) and some common also to other connective tissue diseases (e.g. anti-ssDNA). Since most patients suffering from PSS are not under medical control until clinical manifestations are fully established, only scarce data are available on the dynamics and clinical significance of autoantibodies in the very early stages of this systemic fibrotic disease. The University of California at Davis line 200 (UCD 200) of chickens spontaneously develop a PSS-like disorder with an acute inflammatory stage around 60 days after hatching, leading to fibrosis with fast progression. In order to address a possible correlation between the occurrence and titer of autoantibodies and the initial disease activity, we have chronologically investigated the presence and titer of autoantibodies directed against several human nuclear antigens in this animal strain. In UCD-200 chickens, we found a progressive increase in autoantibodies to histones, to ssDNA and--to a lesser degree--dsDNA with peaks at the age of 60 and 120 days, to poly(I) and poly(G) with a peak at 120 days and an elevation in anti-cardiolipin antibodies. Total immunoglobulin concentrations, anti-Ro, anti-La and anti-Sm showed no significant differences as compared to negative results in healthy normal controls. Our data reveal parallels in the antinuclear antibody (ANA) spectrum between UCD-200 chickens and human autoimmune collagen diseases, but do not reflect the typical ANA spectrum found in the foudroyant form of diffuse scleroderma.(ABSTRACT TRUNCATED AT 250 WORDS)
"The University of California at Davis (UCD) 200/206 chicken model  is an important animal model for vascular changes in SSc. Unlike some animal models, the UCD chicken lines spontaneously develop an inherited scleroderma-like disease exhibiting the entire spectrum of SSc, including vascular occlusion, severe perivascular lymphocytic infiltration of the skin and viscera, fibrosis of skin and internal organs, auto-antibodies against nuclear antigens, anticardiolipin antibodies, anti-endothelial cell antibodies (AECAs), rheumatoid factors and distal polyarthritis [64-66]. "
[Show abstract][Hide abstract] ABSTRACT: Angiogenesis is important in the pathogenesis of systemic inflammatory rheumatic diseases, a family of related disorders that includes rheumatoid arthritis and systemic sclerosis. Rheumatoid arthritis is the rheumatic disease in which the role of angiogenesis has been studied most extensively. However, whereas rheumatoid arthritis is characterized by excessive angiogenesis, the situation is not as clear cut in other rheumatic diseases. For example, systemic sclerosis is characterized by reduced capillary density with insufficient angiogenic responses. Results with angiogenesis inhibitors are controversial, and there is--in parallel--a wide range of upregulated angiogenic factors such as vascular endothelial growth factor. Dysregulation of angiogenesis in systemic sclerosis is accompanied by other pathogenic processes, including fibrosis, autoimmunity and vasculopathy. Animal models with at least partial features of the vasculopathy observed in systemic sclerosis include wound healing models, graft versus host disease models and, in particular, the University of California at Davis line 200 chicken model of systemic sclerosis.
"Early in life, the majority of UCD-200 and 206 sera is positive for anti-cytoplasmic antibody staining on HEp-2 cells, and 60% have detectable rheumatoid factor by the age of 6 month. No reactivity has been observed against Scl-70, RNA, SS-A/Ro, SS-B/La or Sm using test kits destined for diagnostic use in humans (Haynes and Gershwin, 1984; Gruschwitz et al., 1993). It is not known if these autoantibodies have any pathophysiological function or are merely epiphenomena. "
[Show abstract][Hide abstract] ABSTRACT: Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible anymore. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models--albeit rare--reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present chapter describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and -206) with a scleroderma-like disease, and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome.
Advances in Immunology 02/2006; 92:71-117. DOI:10.1016/S0065-2776(06)92002-1 · 5.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many important lessons have been learned from studies of autoimmune diseases in chicken models. It is now quite clear that both cellular and humoral immune responses are important in developing the final picture of autoimmune disease. In the case of the amelanosis of Smyth line (SL) chickens, antibody appears to play the primary role, whereas the sclerosis of University of California/Davis line-200 (UCD-200) birds is mainly mediated by T cells. Chronic thyroiditis of the OS chicken is due to both humoral and cellular effector mechanisms. The Obese strain (OS) chicken is particularly valuable for studies of genetics. Multiple genetic factors converge in producing maximal susceptibility to the development of autoimmune thyroiditis. They include MHC genes responsible for immune recognition; genes affecting thymus development, critical for regulation of the immune response; and genes that control thyroid function, influencing the vulnerability of the target organ to autoimmune attack. The importance of environmental factors, such as dietary iodine, is also strongly supported by studies in the OS chicken. Thus, the birds have provided valuable clues to our understanding of human autoimmune disorders in the past and are expected to do so in the future.
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