The Protective Effect of HLA-DRB1*13 Alleles during Specific Phases in the Development of ACPA-Positive RA

J. van Heemst¹, A.H. Hensvold², X. Jiang², H. van Steenbergen¹, L. Klareskog², T. W. J. Huizinga¹, A.H.M. van der Helm- van Mil¹, A.I. Catrina², René E. M. Toes¹, K. Lundberg² and Diane van der Woude¹, ¹Leiden University Medical Center, Leiden, Netherlands, ²Karolinska Institute, Stockholm, Sweden

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ACPA, human leukocyte antigens (HLA), pathogenesis and risk, rheumatoid arthritis

Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster II

Session Type: ACR Poster Session B

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

Background/Purpose: HLA-DRB1*13 alleles are associated with protection from anti-citrullinated protein antibody (ACPA-)positive rheumatoid arthritis (RA). It is however unknown at which phase of disease development (seroconversion, ACPA maturation, disease onset or outcome) these alleles are most important. We therefore examined the effect of HLA-DRB1*13 on: ACPA-presence (:systemic autoimmunity associated with RA) in individuals with and without RA, on ACPA characteristics and on clinical outcome measures.

Methods: The effect of HLA-DRB1*13 on ACPA-presence in subjects with or without RA was assessed in the Swedish twin registry (n=10748). ACPA characteristics were studied in ACPA-positive RA patients from the Swedish Epidemiological Investigation of RA (EIRA, n=1224) and the Dutch Leiden Early Arthritis Clinic (EAC, n=441). Disease activity at inclusion and disease outcome (DMARD-free sustained remission and radiographic progression) was assessed in RA patients from the EAC.

Results: HLA-DRB1*13 is associated with protection from ACPA-positive RA (prevalence 16% versus 28% in ACPA-negative RA), but not with significant protection from ACPA in individuals without RA (prevalence: 22%, p-value 0.09). HLA-DRB1*13 is associated with lower ACPA-levels (EIRA: 447 U/ml versus 691 U/ml, p-value: 0,0002) and decreased citrullinated epitope recognition (EIRA: p< 0.0001). No association between HLA-DRB1*13 and disease activity or outcome was found.

Conclusion: These data indicate that HLA-DRB1*13 mainly affects the onset of ACPA-positive RA in ACPA-positive non-RA individuals. In RA, HLA-DRB1*13 influences ACPA characteristics, but not the disease course. This implies that therapeutic strategies aimed at emulating the HLA-DBR1*13 protective effect may be most effective in ACPA-positive healthy individuals at risk for RA.

Disclosure: J. van Heemst, None; A. H. Hensvold, None; X. Jiang, None; H. van Steenbergen, None; L. Klareskog, None; T. W. J. Huizinga, None; A. H. M. van der Helm- van Mil, None; A. I. Catrina, None; R. E. M. Toes, None; K. Lundberg, None; D. van der Woude, None.

To cite this abstract in AMA style:

van Heemst J, Hensvold AH, Jiang X, van Steenbergen H, Klareskog L, Huizinga TWJ, van der Helm- van Mil AHM, Catrina AI, Toes REM, Lundberg K, van der Woude D. The Protective Effect of HLA-DRB1*13 Alleles during Specific Phases in the Development of ACPA-Positive RA [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-protective-effect-of-hla-drb113-alleles-during-specific-phases-in-the-development-of-acpa-positive-ra/. Accessed .

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