ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1573

In Vivo Phosphorylation of p38 in Monocytes Is Enhanced in Patients with Axial Spondyloarthritis (axSpA) at the Time of Diagnosis

Antti Kuuliala1,2, Krista Kuuliala1,3, Riitta Koivuniemi2,4, Mari Hämäläinen5, Eeva Moilanen6, Hannu Kautiainen7, Heikki Repo1,3 and Marjatta Leirisalo-Repo2,4, 1Bacteriology and Immunology, University of Helsinki, Helsinki, Finland, 2Rheumatology, Helsinki University Hospital, Helsinki, Finland, 3Helsinki University Hospital, Helsinki, Finland, 4Rheumatology, University of Helsinki, Helsinki, Finland, 5The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland, 6The Immunopharmacology Research Group, Faculty of Medicine and Life Sciences, University of Tampere and Tampere University Hospital, Tampere, Finland, Tampere, Finland, 7Unit of Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Monday, November 6, 2017

Title: Spondyloarthropathies and Psoriatic Arthritis – Pathogenesis, Etiology Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Host response to microbes is considered to contribute to the pathogenesis to axSpA and other HLA-B27 associated diseases. The p38 MAP kinase pathway plays an important role in the resistance of bacterial replication in HLA-B27 expressing human monocytic U937 cells (Sahlberg AS et al: Arthritis Rheum 2007;56:2652). This prompted us to study the phosphorylation of the MAP kinases p38, extracellular signal-regulated kinase (ERK)1/2 and c-Jun-N-terminal kinase (JNK) in patients with axSpA.

Methods: The study comprised 20 patients [10 men, 10 women, mean age 31.1 years (range 22-48), 19/20 patients HLA-B27 positive, time from first period of back pain mean 5.9 years (range 0.3-16), mean BASDAI 4.4 (SD 1.7)] referred to rheumatology unit for diagnostic workup due to back pain. Radiological sacroiliitis was observed in 1/18 patients, and inflammation in sacroiliac joints by MRI was observed in 17/20 patients. The patients were diagnosed to have axSpA fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria. We included 26 patients [7 men, 19 women, mean age 49 years, range 19-79, mean DAS28 4.0 (SD 1.3)] with early untreated RA fulfilling the 2010 ACR/EULAR classification criteria as a disease control group, and 18 adult volunteers (9 men, 9 women, mean age 39 years, range 25-70) as healthy controls. Whole blood phosphospecific flow cytometry was used to reveal phosphorylation of p38, ERK1/2 and JNK in nonstimulated monocytes, and in monocytes stimulated by E. coli-derived lipopolysaccharides (LPS), whole cells of E. coli or lipoteichoic acid (LTA). Fluorescence histograms for monocyte pERK1/2-PE-CF594, pJNK-AlexaFluor647 and pp38-PE-Cy7 were created and fluorescence intensities were expressed as relative fluorescence units (RFU). Phosphorylation capability of MAP kinases was determined by fold-increase, i.e. the ratio of RFU of the stimulated sample to the nonstimulated one. Significance of difference between axSpA and RA patients and healthy subjects was tested by ANCOVA, adjusted for high sensitivity (hs)CRP levels.

Results: Basal phosphorylation level of p38 in axSpA monocytes was significantly higher than that in healthy subjects’ monocytes (P=0.009), while the difference between RA and healthy subjects was not statistically significant. The respective phosphorylation levels of ERK1/2 and JNK did not differ significantly between the 3 subject groups. The fold-increases of p38 phosphorylation in axSpA monocytes upon LPS or E.coli stimulation were significantly lower than those in healthy subjects’ monocytes (P=0.004 and 0.002, respectively), while the respective differences between RA and healthy subjects were not statistically significant. The p38 RFU values of the stimulated monocytes did not differ significantly between the 3 subject groups. The fold-increases of ERK1/2 and JNK phosphorylation did not differ significantly between the 3 subject groups.

Conclusion: Enhanced monocyte baseline phosphorylation of p38 suggests in vivo preactivation of monocytes in patients at the time of diagnosis of axSpA.

Disclosure: A. Kuuliala, None; K. Kuuliala, None; R. Koivuniemi, None; M. Hämäläinen, None; E. Moilanen, None; H. Kautiainen, None; H. Repo, None; M. Leirisalo-Repo, None.

To cite this abstract in AMA style:

Kuuliala A, Kuuliala K, Koivuniemi R, Hämäläinen M, Moilanen E, Kautiainen H, Repo H, Leirisalo-Repo M. In Vivo Phosphorylation of p38 in Monocytes Is Enhanced in Patients with Axial Spondyloarthritis (axSpA) at the Time of Diagnosis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/in-vivo-phosphorylation-of-p38-in-monocytes-is-enhanced-in-patients-with-axial-spondyloarthritis-axspa-at-the-time-of-diagnosis/. Accessed .

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