1,721,066 research outputs found
Something old, something new: biomarkers in rheumatoid arthritis
No full textThe detection of RA in its early stages is often challenging, and the measurement of ACPA levels is crucial. Given the specificity of ACPA for RA, a positive result in any assay has a high predictive value for diagnosis; 40% positivity has been reported using the cyclic citrullinated peptide (CCP) assay and similar or slightly lower percentages by other assays. Unfortunately, with all the assays now available, the frequency of a positive result is lower in early RA — when treatment would be most efficacious — than in later disease. A small increment in the frequency of positive results may be obtained by conducting parallel assays using different citrullinated substrates. In fact, the overlap of the CCP assay with the other tests for ACPA is not complete: sera that are anti-CCP-negative, but positive for antiviral citrullinated peptide, anticitrullinated fibrinogen, or anti-modified citrullinated vimentin antibodies do exist, and have been reported in 2%–7% of tested RA populations.
In the future, the diagnosis of RA could benefit greatly from the gathering of information through the assaying of many variables simultaneously — for example, a cluster of biomarkers associated with genotyping — leading to the more accurate prediction of disease outcome and to more effective, individualized treatment
Multiple Autoantibody Cross-reactivity in Connective Tissue Diseases
No full textNo abstract availabl
IgG subclass profile of anti citrullinated peptide antibodies specific for EBV- and histone-derived citrullinated peptides
No full textNo abstract availabl
Autoantibodies and nephritis: different roads may lead to Rome
No full textOur understanding of antibody-mediated renal damage has not changed drastically in recent years. However, within this framework a lot of new data emerged to change our way of looking at old diseases. For example, APSGN, which in the past has been regarded as a typical CIC-mediated disease, may also show ICs formed in situ. In Goodpasture's syndrome, once considered to be the classical model of autoantibody-mediated disease, it is now realized that nephritogenic T cells play an important role. Complement, formerly thought to be a pathogenic factor in nephritis, is now believed to be crucial for the protection of immune-mediated renal injury. At the same time, components of the fibrinolytic system play a role as autoantibody targets in renal damage, and a disregulation of this pathway may be a mechanism in different renal diseases. Furthermore, new hypotheses are emerging to explain how the immune system interacts with the external world. One of them suggests that a great deal more is involved than the mere discrimination between self and nonself: the immune system is able to handle all elements, even endogenous ones, that pose a potential danger to the host (Matzinger, 1994). Thus, tissues themselves play a central role: when healthy, they may induce tolerance and when distressed, they may stimulate immunity. In this view, autoimmunity can be regarded as a defect in the cross-talk between the immune system and the body tissues, a perspective that opens up fascinating new avenues for research on the mechanisms that regulate the expression of renal antigens in health and disease
Peptidylarginine deiminase 4 and citrullination in health and disease
No full textDeimination is catalyzed by a family of calcium binding enzymes, called peptidylarginine deiminases (PADs). Among these, the PAD4 isoform has been more extensively studied for its role in some autoimmune diseases. PAD4 is localized in the cytoplasm of monocytes, T and B cells, neutrophils, eosinophils and NK cells and can move to the nucleus upon cell activation. PAD4 plays a physiological role in gene regulation via citrullination of histones. In rheumatoid arthritis (RA), PAD4 contributes to the generation of ACPA specific substrates and is itself a target of autoantibodies; alleles of the PADI4 gene confer susceptibility to RA in Asians but not in Caucasians. In multiple sclerosis, extensive deimination of brain proteins is observed in active lesions, but no role for the PADI4 gene in susceptibility to MS has been so far described
The immune response to citrullinated antigens in autoimmune diseases
No full textPost-translational modifications of proteins occur very frequently. One of these modifications, citrullination, is the result of arginine deimination operated by an enzyme, peptidylarginine deiminase (PAD), whose activity is under strict genetic control. Serum antibodies reactive with citrullinated proteins/peptides are a very sensitive and specific marker for rheumatoid arthritis. Genes encoding for PAD enzymes have been investigated in RA: the PADI4 gene confers susceptibility to RA in Japanese patients, but not in Caucasians
Anti-citrullinated protein antibodies (ACPA) and antibodies to exogenous antigens in follow-up study of rheumatoid arthritis patients
No full textAbstract not availabl
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