Naturally occurring antibodies against serum amyloid A reduce IL-6 release from peripheral blood mononuclear cells

作者：Kuret Tadeja; Lakota Katja; Mali Polonca; Cucnik Sasa; Praprotnik Sonja; Tomsic Matija; Sodin Semrl Snezna^*

来源：PLos One, 2018, 13(4): e0195346.

DOI：10.1371/journal.pone.0195346

Serum amyloid A (SAA) is a sensitive inflammatory marker rapidly increased in response to infection, injury or trauma during the acute phase. Resolution of the acute phase and SAA reduction are well documented, however the exact mechanism remains elusive. Two inducible SAA proteins, SAA1 and SAA2, with their variants could contribute to systemic inflammation. While unconjugated human variant SAA1 alpha is already commercially available, the variants of SAA2 are not. Antibodies against SAA have been identified in apparently healthy blood donors (HBDs) in smaller, preliminary studies. So, our objective was to detect antiSAA and anti-SAA1 alpha autoantibodies in the sera of 300 HBDs using ELISA, characterize their specificity and avidity. Additionally, we aimed to determine the presence of anti-SAA and anti-SAA1 alpha autoantibodies in intravenous immunoglobulin (IVIg) preparations and examine their effects on released IL-6 from SAA/SAA1 alpha-treated peripheral blood mononuclear cells (PBMCs). Autoantibodies against SAA and SAA1 alpha had a median (IQR) absorbance OD (A(450)) of 0.655 (0.262-1.293) and 0.493 (0.284-0.713), respectively. Both antiSAA and anti-SAA1 alpha exhibited heterogeneous to high avidity and reached peak levels between 41-50 years, then diminished with age in the oldest group (51-67 years). Women consistently exhibited significantly higher levels than men. Good positive correlation was observed between anti-SAA and anti-SAA1 alpha. Both anti-SAA and anti-SAA1 alpha were detected in IVIg, their fractions subsequently isolated, and shown to decrease IL-6 protein levels released from SAA/SAA1 alpha-treated PBMCs. In conclusion, naturally occurring antibodies against SAA and anti-SAA1 alpha could play a physiological role in down-regulating their antigen and proinflammatory cytokines leading to the resolution of the acute phase and could be an important therapeutic option in patients with chronic inflammatory diseases.

• 出版日期2018-4-4