ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 74

DNA Methylation of the Dual Specificity Protein Phosphatase 22 (DUSP22) Gene Promoter in Plasma of Patients with Seropositive and Seronegative RA

Milena Rodriguez Alvarez1, Lissette Delgado-Cruzata2, Edgardo Guzman3, Wallis Tavarez3, Alorah Bliese2, Tagir Sabirov3, Maria-Jose Jimenez3, Carmen A Oviedo Hilario3, Manuel E. Acosta4, Maria Albarracin2, Carl Cirilli2, Zuleika Parra3, Cristabel Robles Hidalgo3, Christopher Mesa3, Dominyka Bitinaite3, Sabeeda Kadavath3, Ibrahim El Husseini3, Grace Thomas3, Augustas Kavaliauskas3, Kioumars Bolourian Kashi3, Michael Gebeyehu3, Dave Samip3, Pawan Suri3, Menachem Gold3 and Shante Hinson3, 1Rheumatology, SUNY Downstate, Brooklyn, NY, 2Sciences, John Jay College, City University of New York, New York, NY, 3Lincoln Medical and Mental Health Center, Bronx, NY, 4Barry University, Miami, FL

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords:

Session Information

Date: Sunday, October 21, 2018

Title: Rheumatoid Arthritis – Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

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

Background/Purpose:

The Dual specificity protein phosphatase 22 (DUSP22) gene is aberrantly methylated in mononuclear cells in RA, and it has been associated with erosive disease. Increased serum IL-6 and phosphorylated STAT3 levels, which are negatively regulated by DUSP22, have been found in T cells of patients with anticitrullinated peptide autoantibody (ACPA)-negative RA. Pathogenic mechanisms underlying different serotypes in RA are poorly understood. Here, we aim to determine whether plasma nuclear circulating cell-free DNA (ccfDNA) can be used to study DNA methylation of DUSP22 and whether it is associated with serotype and other clinical features of RA.

 

Methods:

This is an exploratory study in which we recruited 21 patients who satisfied the ACR criteria for RA. They were further classified in 14 seropositive (ACPA+ and/or RF+), and 7 seronegative patients (ACPA- and RF-). DNA was extracted from isolated plasma, bisulfite converted and pyrosequenced to determine DNA methylation levels in the promoter region of DUSP22. Statistical analysis was carried out to determine whether DUSP22 DNA methylation in plasma correlated with serotype, index disease activity (CDAI), Simple Erosive Narrowing Score (SENS), Visual Analogue Scale (VAS), neuropathic pain (ID pain), Toronto Clinical Neuropathy Score (TCNS), Neuropathy Symptom Score (NSS), treatment (DMARDs, anti-TNF alpha), and disease duration. Variables were also analyzed by serotype status and the groups were compared using non-parametric tests.

 

Results:

Hypomethylation of the DUSP22 promoter was correlated with an increase in SENS (p=0.02), and NSS (p=0.03) in all RA patients. We found that DUSP22 DNA methylation did not vary for the different treatment groups. While no statistically significant difference was determined in the DNA methylation of DUSP22 between seronegative and seropositive patients, hypomethylation of DUSP22 in seropositives was negatively and significantly correlated with years of disease (p=0.002), SENS (p=0.04), and NSS (p=0.002).  We also found seronegative there was only significantly correlated with NSS (p=0.017).

Conclusion:

While our study has a small samples size, it is the first study to demonstrate that DNA methylation can be measured in ccfDNA of RA patients. We also found that hypomethylation of DUSP22 was correlated with erosive disease, disease duration and neuropathic pain in seropositive patients, and only with neuropathic symptoms in seronegative patients.

  ACPA – and RF-RA ACPA+ and/or RF +RA p-value
Demographics
No. men 2 2 –
No. women 5 12 –
Men age (years) 57.3±6.4 59.0±14.0  
Women age (years) 61.0±8.3 56.7±13.1  
Hispanic 6 12 –
African American 1 2 –
Treatment
DMARDs 6 9 –
Biologics+/-DMARDs 1 5 –
Clinical Characteristics
% ACPA+ 0 94.4% –
% RF+ 0 84.2% –
Disease duration (years) 8.6±14.8 12.1±9.8 0.05
CRP 1.94±3.65 0.78±0.98 0.77
WBC 7.4±2.2 6.8±2.0 0.48
CDAI 20.6±6.7 14.4±10.3 0.11
VAS 3.0±2.7 6.7±1.1 0.01
NSS 5.3±3.4 2.6±2.5 0.04
ID PAIN 4.3±1.4 2.0±1.6 0.008
TCNS 7.7±2.2 4.1±4.0 0.04
SENS 10.6±9.5 25.1±21.8 0.26
DUSP22 DNA methylation (%) 42.5±11.2 37.6±18.7 0.45
Rheumatoid arthritis treatment and DNA methylation of the DUSP22 promoter
    DMARDs   Biologicals   p-value
% DUSP22 meth 39.7 ± 16.8 38.7 ± 16.7  0.851
Pearson correlation with DUSP22 DNA methylation without considering serotype status
  % DUSP22 meth p-value
Disease duration -0.43 0.15
CRP -0.09 0.69
WBC -0.14 0.54
CDAI -0.27 0.25
VAS -0.08 0.72
NSS -0.48* 0.03
ID PAIN -0.22 0.3
TCNS -0.15 0.52
SENS -0.51* 0.02
Pearson correlation with DUSP22 DNA methylation considering serotype status
  ACPA – and RF-RA ACPA+ and/or RF +RA
Disease duration -0.03 -0.94*
CRP -0.47 0.14
WBC -.0.18 -0.19
CDAI -0.46 -0.30
VAS -0.25 -0.18
NSS -0.80* -0.76*
ID PAIN -0.7 -0.29
TCNS -0.37 -0.26
SENS 0.18 -0.58*
*p≤0.05
Disclosure: M. Rodriguez Alvarez, None; L. Delgado-Cruzata, None; E. Guzman, None; W. Tavarez, None; A. Bliese, None; T. Sabirov, None; M. J. Jimenez, None; C. A. Oviedo Hilario, None; M. E. Acosta, None; M. Albarracin, None; C. Cirilli, None; Z. Parra, None; C. Robles Hidalgo, None; C. Mesa, None; D. Bitinaite, None; S. Kadavath, None; I. El Husseini, None; G. Thomas, None; A. Kavaliauskas, None; K. Bolourian Kashi, None; M. Gebeyehu, None; D. Samip, None; P. Suri, None; M. Gold, None; S. Hinson, None.

To cite this abstract in AMA style:

Rodriguez Alvarez M, Delgado-Cruzata L, Guzman E, Tavarez W, Bliese A, Sabirov T, Jimenez MJ, Oviedo Hilario CA, Acosta ME, Albarracin M, Cirilli C, Parra Z, Robles Hidalgo C, Mesa C, Bitinaite D, Kadavath S, El Husseini I, Thomas G, Kavaliauskas A, Bolourian Kashi K, Gebeyehu M, Samip D, Suri P, Gold M, Hinson S. DNA Methylation of the Dual Specificity Protein Phosphatase 22 (DUSP22) Gene Promoter in Plasma of Patients with Seropositive and Seronegative RA [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/dna-methylation-of-the-dual-specificity-protein-phosphatase-22-dusp22-gene-promoter-in-plasma-of-patients-with-seropositive-and-seronegative-ra/. Accessed .

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