For the last two decades, there had been remarkable advancement in understanding the role of complement regulatory proteins in autoimmune disorders and importance of complement inhibitors as therapeutics. Systemic lupus erythematosus is a prototype of systemic autoimmune disorders. The disease, though rare, is potentially fatal and afflicts women at their reproductive age. It is a complex disease with multiorgan involvement, and each patient presents with a different set of symptoms. The diagnosis is often difficult and is based on the diagnostic criteria set by the American Rheumatology Association. Presence of antinuclear antibodies and more specifically antidouble-stranded DNA indicates SLE. Since the disease is multifactorial and its phenotypes are highly heterogeneous, there is a need to identify multiple noninvasive biomarkers for SLE. Lack of validated biomarkers for SLE disease activity or response to treatment is a barrier to the efficient management of the disease, drug discovery, as well as development of new therapeutics. Recent studies with gene knockout mice have suggested that membrane-bound complement regulatory proteins (CRPs) may critically determine the sensitivity of host tissues to complement injury in autoimmune and inflammatory disorders. Case-controlled and followup studies carried out in our laboratory suggest an intimate relation between the level of DAF, MCP, CR1, and CD59 transcripts and the disease activity in SLE. Based on comparative evaluation of our data on these four membrane-bound complement regulatory proteins, we envisaged CR1 and MCP transcripts as putative noninvasive disease activity markers and the respective proteins as therapeutic targets for SLE. Following is a brief appraisal on membrane-bound complement regulatory proteins DAF, MCP, CR1, and CD59 as biomarkers and therapeutic targets for SLE.
[Show abstract][Hide abstract] ABSTRACT: Characterisation of proteins and whole proteomes can provide a foundation to our understanding of physiological and pathological states and biological diseases or disorders. Constant development of more reliable and accurate mass spectrometry (MS) instruments and techniques has allowed for better identification and quantification of the thousands of proteins involved in basic physiological processes. Therefore, MS-based proteomics has been widely applied to the analysis of biological samples and has greatly contributed to our understanding of protein functions, interactions, and dynamics, advancing our knowledge of cellular processes as well as the physiology and pathology of the human body. This review will discuss current proteomic approaches for protein identification and characterisation, including post-translational modification (PTM) analysis and quantitative proteomics as well as investigation of protein–protein interactions (PPIs).
Australian Journal of Chemistry 07/2013; 66(7). DOI:10.1071/CH13137 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The immune system has the challenging tasks to discriminate self from non-self, but also to discern harmless from harmful foreign antigens or entities and to attack and eliminate foreign threats. In the classical view the immune system can be divided into an innate and adaptive branch, where the innate immune system represents a quick first-line defense against pathogens, whereas the adaptive immune system is slower, but more diverse and sophisticated, able to memorize pathogens, and confer long-lasting immunity to the host. The innate immune system relies on recognition of evolutionarily conserved pathogen-associated molecular patterns (PAMPs) by
innate pattern recognition molecules and receptors (PRMs and PRRs), whereas the adaptive immune system is principally trained to recognize foreign molecules and to memorize them by highly adapted, specific receptor molecules.
Comparative Medicine: Anatomy and Physiology, 1 edited by Erika Jensen-Jarolim, 12/2013: chapter 13.1: pages 220-242; Springer., ISBN: ISBN 978-3-7091-1559-6 (ebook)
[Show abstract][Hide abstract] ABSTRACT: All organisms evolved mechanisms to protect themselves against pathogen invasion and hence possess an innate immune system. However, vertebrates have also evolved an additional strategy, the so-called adaptive immune system to further protect themselves against pathogens. In the classical view the immune system can
be divided into an innate and adaptive branch of immunity with distinct function. In contrast to innate defense mechanisms, which occur within minutes, the adaptive immunity is slower and usually needs 4–5 days from the primary encounter with the pathogen to be activated. One hallmark of adaptive immunity is the generation of immunological memory enabling the host to “remember” pathogens for years. As a consequence, the host can respond to a subsequent encounter stronger, very specifically and immediately. Another hallmark of the adaptive immune system is its high antigen-diversity. This is reached by the random a priori generation of a seemingly unlimited repertoire of antigen receptors with different specificities, in contrast to the innate immune cells with a limited number of pathogen recognition receptors.
Comparative Medicine: Anatomy and Physiology., 1 edited by Erika Jensen-Jarolim, 12/2013: chapter 13.2: pages 243-266; Springer., ISBN: ISBN 978-3-7091-1559-6
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