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Abstract Number: 2136

Association of HLA-DQA1*05 with the Presence of Interstitial Lung Disease Independent of Autoantibody Status in Caucasian Patients with Polymyositis and Dermatomyositis

Adam Schiffenbauer1, Sara Faghihi-Kashani2, Terrance P. O'Hanlon1, Willy Flegel3, Sharon Adams3, Ira N. Targoff4, Chester V. Oddis5,6, Rohit Aggarwal7,8, Lisa G Rider1, Steven R. Ytterberg9, Lisa Christopher-Stine10, Sonye K. Danoff11, Paul F. Dellaripa12,13, Ejaz Shamim14, Andrew Mammen15 and Frederick W Miller16, 1Environmental Autoimmunity Group, NIEHS, NIH, Bethesda, MD, 2Environmental Autoimmunity Group, National Institute of Environmental Health, Bethesda, MD, 3Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, 4VA Medical Center, University of Oklahoma Health Sciences Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, 5Rheumatology/Clinical Immunology, Unviersity of Pittsburgh/University of Pittsburgh Medical Center, Pittsburgh, PA, 6Rheum/Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, 7Pediatria II, Reumatologia, PRINTO, Istituto Giannina Gaslini, Genoa, Italy, 8Department of Medicine / Rheumtology, University of Pittsburgh Medical Center, Pittsburgh, PA, 9Rheumatology, Mayo Clinic, Rochester, MN, 10Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 11Medicine/Pulmonary, Johns Hopkins University, Baltimore, MD, 12Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, 13Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA, 149. Department of Neurology, Mid-Atlantic Permanente Research Institute, Kaiser Permanente, Rockville, MD, 15Muscle Diseases Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health, Bethesda, MD, 16Clinical Research Branch / Environmental Autoimmunity Group, NIH, Bethesda, MD

Meeting: ACR/ARHP Annual Meeting 2017

Date of first publication: September 18, 2017

Keywords: , , ,

Session Information

Date: Tuesday, November 7, 2017

Title: Muscle Biology, Myositis and Myopathies Poster

Session Type: ACR Poster Session C

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

Background/Purpose:

Interstitial lung disease (ILD) is a frequent complication and a major contributor to mortality and morbidity in polymyositis and dermatomyositis (PM/DM). Prior studies have linked the presence of anti-synthetase autoantibodies (ASA) and part of the HLA 8.1 ancestral haplotype (AH8.1) to ILD in PM/DM patients. This study aimed to evaluate the contribution of HLA-DQA1*05 to the presence of ILD in Caucasian PM/DM independent of ASA.

Methods:

A total of 82 Caucasian patients with adult-onset PM/DM per Bohan and Peter criteria and with HLA class I (A, B and C) and class II (DRB1 and DQA1) evaluated by sequence-specific oligonucleotide probe hybridization and priming techniques or sequencing methods were included. ILD status was determined by retrospective chart review based on imaging results, lung biopsy, and/or pulmonary function tests. ASA were determined by standard immunoprecipitation methods. AH8.1 was defined as the presence of HLA-A*01, B*08, C*07, DRB1*0301, and DQA1*05. Pearson chi-square (or Fischer exact when appropriate), multiple logistic regression tests and forward stepwise logistic methods were applied. P < 0.05 was considered statistically significant.

Results:

Overall, 27 (33%) had ILD, 29 (35%) were positive for ASA and 29 (35%) carried the AH8.1. ILD was associated with ASA (OR=8.0, 95%CI: 2.83-22.58, P<0.001) and with the AH8.1 (OR=3.66, 95%CI: 1.38-9.67, P=0.009) as expected.  Of the five AH8.1 alleles, HLA-DQA1*05 was the only locus significantly associated with ILD after adjusting for the presence of ASA (OR=5.95, 95%CI: 1.47-24.05, P=0.012). This association remained significant after adjusting for the presence of the other alleles of the AH8.1 and ASA status (OR=12.31, 95% CI: 1.81-83.81, P=0.010). Chi squared tables, categorizing the cohort based on the presence or absence of each AH 8.1 allele, were used to assess the independent effect of HLA-DQA1*05 on risk of ILD conditioned on ASA status and the frequency of ILD was higher in DQA1*05 carriers, however, due to limited power, not all comparisons met statistical significance. Additionally, forward stepwise logistic analysis, while keeping ASA in the model regardless of step, showed that DQA1*05 was the only HLA allele that remained in the best fit model for risk of ILD (OR=5.95, 95% CI: 1.47-24.05, P=0.012). Figure 1 shows the risk of ILD in Caucasian PM and DM patients based on the ASA and DQA1*05 status.  

Conclusion:

HLA-DQA1*05 is associated with an increased risk of ILD in Caucasian PM and DM patients, independent of ASA and other AH8.1 alleles, implying that HLA-DQA1*05 impacts the risk of ILD independently from ASA in Caucasian PM/DM. Thus, HLA-DQA1*05 may be a useful screening test for evaluating the risk of ILD in ASA negative PM/DM patients and may have diagnostic, prognostic and pathogenic implications for myositis-associated ILD that should be further assessed in additional cohorts.

Disclosure: A. Schiffenbauer, None; S. Faghihi-Kashani, None; T. P. O'Hanlon, None; W. Flegel, None; S. Adams, None; I. N. Targoff, None; C. V. Oddis, None; R. Aggarwal, Pfizer Inc, 2,Bristol-Myers Squibb, 2,Mallinckrodt, 2,Genentech and Biogen IDEC Inc., 2,Momenta, 2,Bristol-Myers Squibb, 5,Octapharma, 5,Mallinckrodt, 5; L. G. Rider, None; S. R. Ytterberg, None; L. Christopher-Stine, OptionCare, 5,Mallinckrodt, 5,Inova Diagnostics, Inc., 7; S. K. Danoff, None; P. F. Dellaripa, Genentech and Biogen IDEC Inc., 9,Up to date, 7; E. Shamim, None; A. Mammen, None; F. W. Miller, None.

To cite this abstract in AMA style:

Schiffenbauer A, Faghihi-Kashani S, O'Hanlon TP, Flegel W, Adams S, Targoff IN, Oddis CV, Aggarwal R, Rider LG, Ytterberg SR, Christopher-Stine L, Danoff SK, Dellaripa PF, Shamim E, Mammen A, Miller FW. Association of HLA-DQA1*05 with the Presence of Interstitial Lung Disease Independent of Autoantibody Status in Caucasian Patients with Polymyositis and Dermatomyositis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/association-of-hla-dqa105-with-the-presence-of-interstitial-lung-disease-independent-of-autoantibody-status-in-caucasian-patients-with-polymyositis-and-dermatomyositis/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-hla-dqa105-with-the-presence-of-interstitial-lung-disease-independent-of-autoantibody-status-in-caucasian-patients-with-polymyositis-and-dermatomyositis/