Could antibodies against Serum Amyloid A function as physiological regulators in humans?

Abstract

The natural structuring of the immune system is responsible for the functional physiological state of the body. The development of natural autoantibodies involved in homeostasis relies on the ability to distinguish between exposed/masked and altered/non-altered self antigens. The objectives of this article were to address the relationships between antigen and autoantibodies against serum amyloid A (SAA), define SAA protein concentrations in 219 blood donor (BD) sera and determine their autoantibody levels and search for possible clinical associations with autoimmune and thrombotic diseases. Just recently, an increasing number of reports have indicated significantly decreased levels of autoantibodies against pro-inflammatory molecules, such as anti-TNF-alpha, anti-IL-6, or anti-CRP found in diseased conditions, as compared to healthy donors, or even to less severe disease conditions. In accord with this line of thought, our data indicate a predominant presence of anti-SAA autoantibodies in healthy BDs (above 95% as tested by the immunoblot analysis, n = 41). Using ELISA, high levels of anti-SAA antibodies were confirmed with a median OD = 0.996 for the BD group (n = 219). This suggests that anti-SAA antibodies might have a physiological role in homeostasis and/or the innate immune system and could actually be a part of the natural antibody repertoire. Significantly, lower median levels were found in patients with arterial thrombosis. Based on 219 BD sera, we could establish a new median value of 20 μg/ml for SAA antigen and a cut-off value of 114.7 μg/ml (97.5th percentile). Significantly, higher concentrations of SAA were observed for antiphospholipid syndrome, rheumatoid arthritic, and SLE patients.

Keywords::

• Natural autoantibodies
• serum amyloid A
• acute phase
• anti-SAA antibodies
• homeostasis

Acknowledgments

We would like to especially thank Prof. Ernst Malle from the Medical University of Graz, Austria, for the generous contribution of anti-SAA antibodies developed against eight synthetic peptides of SAA. We gratefully acknowledge the work of Ms. Dalida Vizjak for her excellent technical contribution. Support for this study was obtained from funding provided by the Ministry of Higher Education, Science and Technology, Slovenia (#P3-0314 to B.R.), the Austrian Ministry of Science and Research (GEN-AU project BIN to G.G.T.), and the European Commission (MC-IRG #28414 to S.S-S.). This work was supported by the Ministry of High Education, Science, and Technology of Slovenia, (#P3 0314 to B.R.), the Austrian Ministry of Science and Research (GEN-AU project BIN to G.G.T.) and the European Commission (#028414 MC-IRG to S.S.-S.).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.