Background/Purpose : Interstitial pneumonia (IP) is one of the most critical complications in rheumatoid arthritis (RA). Severe IP is developed in zymosan-treated SKG mice, and this IP is completely blocked by neutralization of granulocyte macrophage colony-stimulating factor (GM-CSF) (Shiomi A, et al. J Immunol. 2014;15;193(2):849-59). GM-CSF induces expression of soluble vascular endothelial growth factor (VEGF) receptor-1 from human monocytes (Eubank TD, et al. Immunity. 2004;21(6):831-42). Here we aimed to explore the associations between IP and biomarkers including GM-CSF, VEGF, and circulating monocyte count in biologic-naive patients with RA.

Methods : Consecutive biologic-naive patients with RA were enrolled in our prospective cohort study at the timing of initiating biologics. Our cohort started in February 2010, and the patients were analysed as of April 2012. Before initiating biologics, we evaluated chest X-rays for all of the patients, and if IP was suspected, a chest computed tomographic (CT) scan was taken. At the enrollment of our cohort we assessed variables including the patients’ characteristics (sex, age, disease duration, prednisolone dose, methotrexate dose, Clinical Disease Activity Index, Health Assessment Questionnaire-Disability Index) and blood biomarkers (GM-CSF [pg/mL], VEGF [pg/mL], TNF-α [pg/mL], Interleukin(IL)-6 [pg/mL], IL-17 [pg/mL], osteopontin [ng/mL], C-reactive protein [mg/dL], white blood cell count [/μL], neutrophil count [/μL], and monocyte count [/μL]) to extract factors associated with CT scan-proven IP using univariate analyses. The extracted factors were entered into a multivariate logistic regression model to obtain factors associated with IP.

Results : A total of 127 patients (108 females and 19 males) were included in our study. The mean age and disease duration of the patients were 56.2±12.9 years and 6.7±7.7 years, respectively. CT scan-proven IP was noted in 17 patients. Prednisolone was used in 33 patients and methotrexate was used in 110. In the univariate analyses, sex, age, prednisolone dose, methotrexate dose, GM-CSF, VEGF, and monocyte count were significantly associated with IP (P<0.05). In the multivariate analyses, age (OR 1.081, 95% CI 1.010-1.174), methotrexate dose (OR 0.820, 95% CI 0.686-0.970), and monocyte count (OR 1.005, 95% CI 1.001-1.010) were identified as factors associated with IP.

Conclusion : The large number of circulating monocytes as well as advanced age and low methotrexate dose is significantly associated with IP in biologic-naive patients with RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/circulating-monocyte-count-is-significantly-associated-with-interstitial-pneumonia-in-biologic-naive-patients-with-rheumatoid-arthritis-a-single-center-prospective-cohort-study-keio-first-bio-cohort/