OA28 The use of ACE and sIL2-R in a large tertiary cohort of patients with multi-system sarcoidosis
Authors: Hughes Mark , Bechman Katie , Roy Ritika , Omar Mariam , Mehta Daksh , Nagra Deepak , Walsh Sarah , Birring Surinder S , Sado Daniel M , Brex Peter A , Galloway James 
Published: April 2024

Abstract

Background/Aims
Sarcoidosis is a systemic inflammatory disorder characterised by the formation of non-caseating granulomas, and can affect almost any organ, ranging from self-limiting to a chronic and progressive disease. There are no validated biomarkers that help establish diagnosis or monitor disease progression. Serum Angiotensin-Converting Enzyme (ACE) is used in clinical practice despite some studies reporting a poor reflection of disease activity. Soluble interleukin 2 receptor (sIL-2R) is being used with increasing frequency and may be a useful tool in establishing diagnosis and monitoring disease progression. Our objectives were to evaluate the use of ACE and sIL2-R in a large tertiary cohort of patients with multisystem sarcoidosis.

Methods
This was an observational cohort study. Patients with a confirmed diagnosis of sarcoidosis at King’s College Hospital between 2013 and 2023 were identified. Demographics, symptoms onset, clinical features, ACE, sIL2-R, high-resolution computed tomography (HRCT), Positron emission tomography-computed tomography (PET-CT), histology and immunomodulating therapy were extracted from electronic health records. Cross sectional correlations between ACE and sIL2-R was assessed by Spearman’s correlation coefficient (rs).

Results
Data were extracted for 196 individuals diagnosed with sarcoidosis. The mean age was 55 (SD 16) with a female and black predominance (table 1). A prior exposure risk of silica or dust was identified in 5 individuals. At diagnosis the most frequently reported organ involvement was lung (65%), eye (20%), musculoskeletal (13%) and skin (12%). Organ involvement on PET-CT was seen in 77%. 22% had interstitial lung disease (ILD) confirmed on HRCT and 3% had myocarditis on cardiac MRI. Steroids were commenced in 56%, with a mean dose of 19mg (SD 13mg). The mean duration of follow up was 7 years (IQR 2.9-14.4), 11% developed symptoms suggestive of new organ involvement, 7% had PET-CT evidence of new organ involvement, 4% had evidence of ILD progression and 14% underwent re-initiation or escalation of steroid therapy. 42% (n = 82) had results for both sIL2-R and ACE biomarkers. The median ACE was 55u/L (IQR 40-83) and sIL2-R 1781ng/L (IQR 1328-2436). 50% (41/82) had a sIL2-R &gt;1800ng/L and 59% (48/82) had an ACE &gt;50u/L. Interestingly, 32% (13/41) with a sIL2-R &gt;1800 had a normal ACE and 42% (20/41) with an ACE &gt;50 had a normal sIL2-R results. sIL2-R correlated with ACE (rs = 0.34, p = 0.0018). There was no significant difference in ACE levels in those taking ACE inhibitors (n = 9) compared to those (n = 73) not: 55u/L (IQR 41-83) versus 39u/L (IQR 30-65) p = 0.30.

Conclusion
sIL2-R significantly correlated with serum ACE, although the rs value is not particularly strong, suggesting other factors may be influencing the relationship. These biomarkers represent different aspects of the disease; serum ACE reflects granulomatous inflammation whilst sIL2-R implies immune system activation and T-cell involvement, which may explain our findings.

Disclosure
M. Hughes: None. K. Bechman: Honoraria; UCB, Viforpharma. Grants/research support; NIHR, Versus Arthritis/Pfizer. R. Roy: None. M. Omar: None. D. Mehta: None. D. Nagra: None. S. Walsh: None. S.S. Birring: None. D.M. Sado: None. P.A. Brex: None. J. Galloway: Honoraria; Abbvie, Biovitrum, Bristol Myers Squib (BMS), Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi, UCB.