Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Pituitary Tumor-Transforming 1 Interacting Protein (PTTG1IP) Is a Novel Target for Autoantibodies in RA
Rodrigues, Hanna Maciejewska, Karouzakis, Emmanuel, Hemmatazad, Hossein, Gay, Renate E., Michel, Beat A., Neidhart, Michel, Gay, Steffen
The identification of novel autoantigens in RA is important for a better understanding of specific disease mechanisms as well as for diagnostic purposes. Pituitary tumor-transforming 1 interacting protein (PTTG1IP) is a co-activator of transcription and is regulated by Runx2, the major regulator of bone morphogenesis.
A modified serological analysis of recombinant cDNA expression libraries (SEREX) using cDNA derived from RA synovium was used for the identification of novel autoantigens. For screening of peptides reactive with autoantibodies synovial fluid from a RA patient was used. An ELISA was established and used to assess the levels of the identified anti-PTTG1IP autoantibodies in synovial fluids and sera from RA (n=30 and 33) and osteoarthritis (OA) (n=14 and 38) patients and in the sera of healthy individuals (n=37). The expression of PTTG1IP was analysed in RA (n=5) and OA (n=4) synovial tissues by Western blot and immunohistochemistry.
PTTG1IP was detected among 18 other novel autoantigenes by the SEREX method. The levels of PTTG1IP reactive autoantibodies were present in 53% (AU range 0275, mean ± SEM 43 ± 8) of synovial fluids from RA patients and differed significantly from OA patients (p<0.05). Only 7% of synovial fluids from OA patients were positive for anti-PTTG1IP autoantibodies (AU range 018, mean 2 ± 1). Most interestingly, anti-PTTG1IP autoantibodies were detected in 43% of synovial fluids from rheumatoid factor (RF) negative RA patients (AU range 035, mean 12 ± 5) and in 40% of anti-citrulinated antibodies (anti-CCP) negative RA patients (AU range 035, mean 12 ± 6). The levels of anti-PTTG1IP autoantibodies in sera of RA patients were significantly higher compared to OA (324 ± 49 vs 80 ± 17, p<0.01) while did not differ significantly from the healthy controls (235 ± 33). PTTG1IP protein was expressed to a similar extent in both RA and OA synovial tissues as assessed by Western blot (RA 125 ± 20 AU vs OA 100 ± 40 AU) and confirmed by immunohistochemistry.
Anti-PTTG1IP autoantibodies are also present in the RF- as well as anti-CCP-negative synovial fluids, and therefore, represent a novel promising candidate for defining a specific subset of RA patients. Since PTTG1IP has been suggested to play a role in osteoblast differentiation, and autoantibodies against PTTG1IP were detected at increased levels in RA patients, it might be speculated that these autoantibodies may interfere with osteoblast differentiation and attempted repair processes in the affected joints.
To cite this abstract, please use the following information:
Rodrigues, Hanna Maciejewska, Karouzakis, Emmanuel, Hemmatazad, Hossein, Gay, Renate E., Michel, Beat A., Neidhart, Michel, et al; Pituitary Tumor-Transforming 1 Interacting Protein (PTTG1IP) Is a Novel Target for Autoantibodies in RA [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1988