Date: Sunday, November 5, 2017
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  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
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.
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.
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 January 17, 2022.
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