Author/Editor     Kuret, Tadeja; Lakota, Katja; Mali, Polonca; Čučnik, Saša; Praprotnik, Sonja; Tomšič, Matija; Sodin-Šemrl, Snežna
Title     Naturally occurring antibodies against serum amyloid A reduce IL-6 release from peripheral blood mononuclear cells
Type     članek
Vol. and No.     Letnik 13, št. 4
Publication year     2018
Volume     str. 1-20
ISSN     1932-6203 - PloS one
Language     eng
Abstract     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 anti- SAA 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 anti- SAA 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 physiologica l role in down-regu lating their antigen and proinflammat ory cytokines leading to the resolution of the acute phase and could be an important therapeutic option in patients with chronic inflammatory diseases.
Keywords     serum amyloid A
mononuclear cells
peripheral blood
serumski amiloid A
mononuklearne celice
periferna kri