B cell infiltration in systemic sclerosis–associated interstitial lung disease

Background: Interstitial lung disease in systemic sclerosis (SSc-ILD) is one of the most severe complications of systemic sclerosis (SSc) and is the main cause of mortality. In this study, we aimed to explore the key genes in SSc-ILD and analyze the relationship between key genes and immune cell infiltration as well as the key genes relevant to the hallmarks of cancer.Methods: Weighted gene co-expression network analysis (WGCNA) algorithm was implemented to explore hub genes in SSc-ILD samples from the Gene Expression Omnibus (GEO) database. Logistic regression analysis was performed to screen and verify the key gene related to SSc-ILD. CIBERSORT algorithms were utilized to analyze immune cell infiltration. Moreover, the correlation between the key genes and genes relevant to cancer was also evaluated. Furthermore, non-coding RNAs (ncRNAs) linking to PTGS2 were also explored.Results: In this study, we first performed WGCNA analysis for three GEO databases to find the potential hub genes in SSc-ILD. Subsequently, we determined PTGS2 was the key gene in SSC-ILD. Furthermore, in CIBERSORT analyses, PTGS2 were tightly correlated with immune cells such as regulatory T cells (Tregs) and was negatively correlated with CD20 expression. Moreover, PTGS2 was associated with tumor growth. Then, MALAT1, NEAT1, NORAD, XIST identified might be the most potential upstream lncRNAs, and LIMS1 and RANBP2 might be the two most potential upstream circRNAs.Conclusion: Collectively, our findings elucidated that ncRNAs-mediated downregulation of PTGS2, as a key gene in SSc-ILD, was positively related to the occurrence of SSc-ILD and abnormal immunocyte infiltration. It could be a promising factor for SSc-ILD progression to malignancy.

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POS0858 POTENTIAL EFFICACY PREDICTORS OF ANTI-B-CELL THERAPY IN THE PATIENTS WITH SYSTEMIC SCLEROSIS ASSOCIATED WITH INTERSTITIAL LUNG DISEASE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2313 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 683.2-684

Author(s):

O. Koneva ◽

L. P. Ananyeva ◽

L. Garzanova ◽

O. Desinova ◽

O. Ovsyannikova ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Correlation Analysis ◽

Cell Therapy ◽

Lung Disease ◽

B Cell ◽

Disease Duration ◽

Potential Efficacy ◽

Group A ◽

Group B

Background:Rituximab (RTM) is considered as a promising therapeutic agent for treatment of With Interstitial Lung Disease (ILD) in the patients with systemic sclerosis (SSc). However, the limited number of RTM-treated patients, considerably varying dose regimens, cumulative doses and observation periods, lack of data on potential predictors of RTM therapy response do not allow univocal conclusions on RTM efficacy or definitive recommendations on RTM use in the patients with SSc.Objectives:The study of potential efficacy predictors of anti-B-cell therapy in the patients with SSc associated with ILD.Methods:90 patients with SSc-ILD verified by multispiral computed tomography were enrolled to the study and received RTM therapy for 12-42 months at cumulative dose 2.9±1.1 grams (disease duration 5.9±4.8 years, diffused/limited SSc 1.3/1, average age 47 ± 13.6 years, females 83%). All patients received low or moderate dose glucocorticoids. 45 patients received RTM in addition to immunosuppressive therapy (cyclophosphamide and mycophenolate mofetil) because of inadequate efficacy of immunosuppressants. After evaluation of FVC trends in the patients receiving RTM the overall study population was divided into two patient groups for the analysis: group A (n=35) comprised the patients with ≥10% FVC increase (disease duration 6.1±5.8 years, diffused/limited SSc 1,3/1, average age 50±12 years, females 86%, cumulative RTM dose 3.2±1.24 grams), and group B (n=11) comprised the patients with ≥5% FVC decrease (disease duration 5.2±4, diffused/limited SSc 0.8/1, average age 43±16, females 72%, cumulative RTM dose 2.5±0.99 grams). Subsequently correlation analysis was made to clarify the association between delta FVC and a number of clinical (age, gender, duration and form of SSc, modified skin count, presence of gastroesophageal reflux, mPAP, SSc activity (EScSG, points), cumulative RTM dose, immunosuppressive therapy) and laboratory parameters (ESR, ANA-НЕР-2, a-Scl-70, CRP, B cell count).Results:In the overall patient population RTM therapy was associated with significant FVC increase from 77.0±19.9 % to 84.7±20.9% (р=0.000000), with median FVC increment 6.6% [0;14.1].In group A FVC increased from 75.3±19.9 to 94.3±20.4) (р=0.000000), with median FVC increment 16.3 [12.6; 24.7].In group B FVC decreased from 82.5 ±23.2 to 72,3±19.4 (р=0,000176), with median FVC decrement 10.4% [-13.4; -6].Correlation analysis in groups A and B showed significant association of between delta FVC and the patient age (R=0.36), cumulative RTM dose (R=0.34) and EScSG during the last examination (1.2±.,0 and 3.1±1.4 in groups A and B, respectively; R=-0.42).No significant correlation between delta FVC and any other tested parameters was found.Conclusion:Therefore, older patients who received the cumulative rituximab dose more than 3 grams with suppressed SSc activity achieved greater FVC increase at the background of therapy. These data allow to consider the above parameters as potential predictors of response to anti-B-cell therapy in the patients with SSc-ILD.Disclosure of Interests:None declared

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