Article
Serum progranulin antibodies in RA patients associated with severe course of disease
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Published: | September 12, 2014 |
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Background: Serum autoantibodies such as rheumatoid factor (RF) or anti-cyclic-citrullinated autoantibodies (ACCP) have been proved to have prognostic relevance for rheumatoid arthritis (RA) and its course of disease. Progranulin-autoantibodies (PGRN-Abs) have been detected in sera of patients suffering from rheumatologic disorders such as psoriatic arthritis, large vessel vasculitis, and crohn`s disease. Here we have conducted a study to evaluate the prevalence of PGRN-Abs and its possible impact on course of disease in a representative cohort of RA patients
Methods: From 1/2012 till 12/2013 sera of 307 RA patients were collected and analyzied for PGRN-Abs with ELISA (as previously published [1]) due toa prospective, blinded, non-randomized study design. 56 RA patients recieved serial serum blood checks for serum PRGN-Abs in intervals of 3 to 6 months.114RA patients out of 307 have been treated by TNFa-inhibitor (TNFi). All RA patients fullfilled the ACR-criteria of 1987 and the the revised diagnosis critera from 2011 for RA, 45 RA patients have been newly diagnosed for RA during the study period. From all RA patients clinical characteristics concerning age, gender, HAQ, DAS28, treatment history including TNFi-failure, radiological joint imaging, and RF/ACCP-status were availiable.
Results: The frequency of PRGN-Abs in RA patients was 26.6%. Figure 1 [Fig. 1] shows significantly higher prevalence of PRGN-Abs in RA patients with erosive joint disease (§ p=0.026) and higher Larsen score ($ p=0.032) as well as in patients with positive RF-IgM (*p=0.0001), but not for ACCP. RA patients (n=114) with TNFi-failure (defined as discontinuation the TNFi within 6 months due to missing efficacy) were tested significantly more frequent for PRGN-Abs vs. TNFi-responders (TNFi+, #p=0.001). DAS28 (3.87 vs. 3.48, p=0.041) but not HAQ values were significantly higher in PRGN-Abs positive patients. The stratification into disease duration of RA has documented no significant difference (96.7 vs. 99.2 months, p=0.86). Serial serum checks of PRGN-Abs in all 56 RA patients showed no influence of PRGN-Abs due to treatment modality (data not shown).
Conclusion: The presence of PRGN-Abs showed a clear association with more severe course of RA disease. The PRGN-Abs associated TNFi-failure seems to reflect the proinflammatory situation, butthe phenomenonhas to be confirmed in a larger cohort.
References
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- Thurner L, Zaks M, Preuss KD, Fadle N, Regitz E, Ong MF, Pfreundschuh M, Assmann G. Progranulin antibodies entertain a proinflammatory environment in a subgroup of patients with psoriatic arthritis. Arthritis Res Ther. 2013;15(6):R211. DOI: 10.1186/ar4406