Autoantibodies to the hPOP1 and Rpp25/38 Components of the Th/to Complex Identify a Subgroup of Systemic Sclerosis (SSc) Associated Interstitial Lung Disease (ILD) and Antibodies to hPOP1 Are Associated with Reduced Survival

Jennifer G Walker¹, Mandana Nikpour², Molla Huq³, Karen Patterson¹, Peter Roberts-Thomson⁴, Susanna Proudman⁵, Wendy Stevens⁶, Susan Lester⁷, Maureen Rischmueller⁸, Jane Zochling⁹, Joanne Sahhar¹⁰, Peter Nash¹¹, Janet Roddy¹², Catherine Hill¹³, Marie Hudson¹⁴, Murray Baron¹⁵, Janet E. Pope¹⁶, Maureen D. Mayes¹⁷, Shervin Assassi¹⁸, Michael Mahler¹⁹ and Marvin J. Fritzler²⁰, ¹Flinders University of South Australia, Adelaide, Australia, ²Melbourne University, Melbourne, Australia, ³Department of Medicine (Rheumatology), Melbourne University, Melbourne, Australia, ⁴Immunology, Flinders University of South Australia, Adelaide, Australia, ⁵University of Adelaide, Adelaide, Australia, ⁶Rheumatology, St. Vincent’s Hospital, Melbourne, Australia, ⁷Queen Elizabeth Hospital, Adelaide, Australia, ⁸Medicine, University of Adelaide, Adelaide, Australia, ⁹Menzies Institute for Medical Research, Tasmania, Hobart, Australia, ¹⁰Department of Rheumatology, Monash Medical Centre, Melbourne, Australia, ¹¹University of Queensland, Brisbane, Australia, ¹²Royal Perth Hospital, Perth, Australia, ¹³Medicine, The University of Adelaide, Adelaide, Australia, ¹⁴Division of Rheumatology, Jewish General Hospital, Lady David Institute for Medical Research, Montreal, QC, Canada, ¹⁵Medicine, McGill University, Quebec, Montreal, QC, Canada, ¹⁶Department of Medicine, Division of Rheumatology, University of Western Ontario, St Joseph's Health Care, London, ON, Canada, ¹⁷Internal Medicine/Rheumatology, University of Texas Health Science Center at Houston, Houston, TX, ¹⁸University of Texas McGovern Medical School, Houston, TX, ¹⁹Research and Development, Inova Diagnostics, San Diego, CA, ²⁰Medicine, University of Calgary, Calgary, AB, Canada

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Autoantibodies and scleroderma

Session Information

Date: Sunday, November 5, 2017

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Clinical Aspects and Therapeutics I

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: The clinical associations of anti-Th/To antibodies (Abs) are not fully established, and until recently immunoprecipitation (IP) was the only reliable assay. Using IP, anti-Th/To Abs are mostly detected in SSc but other reported associations include ILD. Our objective was to examine clinical correlates of anti-Th/To Abs targeted against three different proteins associated with the Th/To autoantigen complex in SSc. We used a commercially available hPOP1 immunoblot and a recently described Rpp25 and Rpp38 chemiluminescence assay in a multinational cohort of SSc.

Methods: Cross sectional retrospective study including 1312 patients from the Australian Scleroderma Cohort study (ASCS), Canadian Scleroderma Research Group (CSRG) and the Genetics versus Environment in Scleroderma Outcome Study (GENISOS). Demographic and clinical variables were harmonized and sera tested for anti-Th/To Abs using hPOP1 (EUROLINE, Eurimmun, Lubeck, Germany) and Rpp25/38 (QUANTA Flash Assay, Inova Diagnostics Inc, San Diego, CA). Rpp25/38 was defined as positive if either one or both autoantibodies were present. ILD was determined by high resolution CT chest (HRCT) or a published algorithm [1] which allows diagnosis of ILD by chest X-ray showing increased interstitial markings or fibrosis and/or physician reported “velcro-like crackles” when HRCT is not available. Descriptive statistics summarise baseline demographic and clinical variables and Kaplan Meier analyses were used to assess survival

Results:

Patients had median (interquartile range) age at disease onset 46.3y (18.6) and disease duration 5.1y (11.4) at recruitment. hPOP1 was positive in 2.4% and Rpp25/38 was positive in 4.5% patients. Notably hPOP1 and Rpp25/38 identified overlapping patient populations (p<0.001). Median age of disease onset for hPOP1 patients was 48.9y (23.3) and for Rpp25/38 patients was 48.8y (17.3).

hPOP1 was associated with ILD on HRCT chest (OR:5.16; p=0.02) but not ILD by algorithm (OR:1.19; p= 0.642). hPOP1 was negatively associated with centromere Abs (CENP) (OR:0.24, p=0.018) and positively associated with PM75/100 (OR: 3.07, p=0.01) ,and Ro52/TRIM21 (OR: 3.18, p=0.002). hPOP1 was not associated with Scl-70 (p=0.089).

Fifty patients (4.0%) were Rpp25 positive and 14 patients (1.1%) Rpp38 positive with strong correlation between the two (p <0.001; rho=0.72). Rpp25/38 was associated with ILD detected by HRCT (OR:3.04; p=0.009) and by algorithm (OR: 2.01 p=0.01). Rpp25/38 was negatively associated with CENP (OR: 0.08, p<0.001) and Scl-70 (OR: 0.19, p=0.020).

Survival was reduced in hPOP1 positive patients (p<0.001), especially when ILD was present. Rpp25/38 and hPOP1 positivity was not associated with pulmonary hypertension nor other disease manifestations.

Conclusion:

In a large multinational SSc cohort autoantibodies to the hPOP1 and Rpp25/38 components of Th/To were found infrequently and appeared to identify two ILD populations. hPOP1 positivity was associated with ILD on HRCT chest and reduced survival while Rpp25/38 positivity was associated with ILD on HRCT and by clinical algorithm and testing may therefore identify those with differing lung involvement.

1. Arthritis Care Res (Hoboken), 2012. 64(4): p. 519-24.

Disclosure: J. G. Walker, None; M. Nikpour, I have received, either directly, or indirectly through close research collaborations, research support from the following companies: Actelion, GSK, Pfizer, BMS, UCB, Astra Zeneca, Janssen., 2,I have presented for UCB as a speaker. I have consulted for Eli Lilly., 5; M. Huq, None; K. Patterson, None; P. Roberts-Thomson, None; S. Proudman, Actelion Pharmaceuticals US, 2,GlaxoSmithKline, 2; W. Stevens, None; S. Lester, None; M. Rischmueller, None; J. Zochling, None; J. Sahhar, None; P. Nash, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 5,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 8,AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, 2; J. Roddy, None; C. Hill, None; M. Hudson, None; M. Baron, None; J. E. Pope, AbbVie, Amgen, Bayer, BMS, Celtrion, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, UCB, 5,Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, 2; M. D. Mayes, None; S. Assassi, Bayer Healthcare, 2,Biogen Idec, 2,Reata, 5,Boehringer Ingelheim, 5; M. Mahler, Inova Diagnostics, Inc., 3; M. J. Fritzler, Inova Diagnostics, Inc., 5.

To cite this abstract in AMA style:

Walker JG, Nikpour M, Huq M, Patterson K, Roberts-Thomson P, Proudman S, Stevens W, Lester S, Rischmueller M, Zochling J, Sahhar J, Nash P, Roddy J, Hill C, Hudson M, Baron M, Pope JE, Mayes MD, Assassi S, Mahler M, Fritzler MJ. Autoantibodies to the hPOP1 and Rpp25/38 Components of the Th/to Complex Identify a Subgroup of Systemic Sclerosis (SSc) Associated Interstitial Lung Disease (ILD) and Antibodies to hPOP1 Are Associated with Reduced Survival [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/autoantibodies-to-the-hpop1-and-rpp2538-components-of-the-thto-complex-identify-a-subgroup-of-systemic-sclerosis-ssc-associated-interstitial-lung-disease-ild-and-antibodies-to-hpop1-are-associat/. Accessed .

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