Anti-SAA1 monoclonal antibody, clone mc1

Serum amyloid A (SAA) and 5100 (S100A8, S100A9 and S100A12) proteins were previously identified as biomarkers of interest for rheumatoid arthritis (RA). Among SAA family, two closely related isoforms (SAA-1 and SAA-2) are linked to the acute-phase of inflammation. They respectively exist under the form of three (alpha, beta, and gamma) and two (alpha and beta) allelic variants. We developed a single run quantitative method for these protein variants and investigated their clinical relevance in the context of RA. The method was developed and validated according to regulations before being applied on plasma coming from RA patients (n = 46), other related inflammatory pathologies (n = 116) and controls (n = 62). Depending on the activity score of RA, SAA1 isoforms (mainly of SAA1 alpha and SAA1 beta subtypes) were found to be differentially present in plasma revealing their dual role during the development of RA. In addition, the weight of SAA1 alpha in the total SAA response varied from 32 to 80% depending on the pathology studied. A negative correlation between SAA1 alpha and SAA1 beta was also highlighted for RA early-onset (r = -0.41). SAA2 and S100A8/S100A9 proteins were significantly overexpressed compared to control samples regardless of RA stage. The pathophysiological relevance of these quantitative and qualitative characteristics of the SAA response remains unknown. However, the significant negative correlation observed between SAA1 alpha and SAA1 beta levels in RA early-onset suggests the existence of still unknown regulatory mechanisms in these diseases.

Although the liver is the primary site of cytokine-mediated expression of acute-phase serum amyloid A (SAA) protein, extrahepatic production has also been reported. Besides its role in amyloidosis and lipid homeostasis during the acute-phase, SAA has recently been assumed to contribute to bone and cartilage destruction. However, expression of SAA in human osteogenic tissue has not been studied. Therefore, we first show that SAA 1 (coding for the major SAA isoform) but not SAA2 transcripts are expressed in human trabecular and cortical bone fractions and bone marrow. Next, we show expression of (i) IL-1, IL-6, and TNF receptor transcripts; (ii)the human homolog of SAA-activating factor-1 (SAF-1, a transcription factor involved in cytokine-mediated induction of SAA genes); and (iii) SAA 112 transcripts in non-differentiated and, to a higher extent, in osteoblast-like differentiated human mesenchymal stem cells. Third, we provide evidence that human osteoblast-like cells of tumor origin (MG-63 and SAOS-2) express SAF-1 under basal conditions. SAA1/2 transcripts are expressed under basal conditions (SAOS-2) and cytokine-mediated conditions (MG-63 and SAOS-2). RT-PCR, Western blot analysis, and immunofluorescence technique confirmed cytokine-mediated expression of SAA on RNA and protein level in osteosarcoma cell lines while SAA4, a protein of unknown function, is constitutively expressed in all osteogenic tissues investigated.