Background/Purpose: The lung disease associated with systemic JIA (SJIA-LD) remains poorly understood. Measurement of cytokine levels in bronchoalveolar lavage fluid (BALF) may offer insights into disease pathogenesis, activity, and progression. However, there is currently limited data on the bronchoalveolar inflammatory environment in children with SJIA-LD. The purpose of the study was to measure levels of proinflammatory cytokines and chemokines in BALF from patients with SJIA-LD.

Methods: Children with SJIA-LD were included in the study at the time of diagnostic bronchoscopy as part of routine clinical care. As controls we included patients undergoing routine bronchoscopy for tracheostomy surveillance or other known inflammatory diseases, including SJIA without LD, autoimmune alveolar proteinosis, IBD with lung disease, and lymphoma. Children from the control group were divided into inflammatory (IC, n=9) and non-inflammatory (NIC, n=7) controls based on underlying disease. Interleukin-6, 8 and 18, S100A8/9, S100A12, CD25, CCL25, CCL17, CCL11, MMP7 and CXCL-9 were measured by ELISA or Multiplex.

Results: BALF samples were obtained from 14 patients with SJIA-LD (mean age 7.4±1.98 years and disease duration 4.4±0.9 years) and 16 patients without SJIA-LD (mean age 8.6±0.24 years). Seven (50%) SJIA-LD patients required O2 support intermittently or continuously and one patient required BiPAP. Serial samples were obtained for two patients before and after whole lung lavage and BMT, respectively.BALF levels of IL-18, CD-25, CCL-11 and MMP-7 were significantly elevated in patients with SJIA-LD compared to controls, while CXCL-9 was significantly higher in controls and IL-6 and IL-8 were significantly higher in the NIC group (Table 1). Levels of CD-25, CXCL-9, CCL-11 and CCL-17 were undetectable in most patients from both groups, but detection of CD25 (χ2=2.16, p= 0.0027) occurred more often in SJIA-LD. Linear regression analysis didn’t show the relationship between BALF IL-18 level and disease duration (p=0.15), oxygen requirement (p=0.11), dose of Anakinra (p=0.4) or plasma levels of ferritin (p=0.9), CXCL-9 (p=0.6) and IL-18 (p=0.9). However, there was a direct relation with daily prednisone dose (p=0.03, CI 13.93 to 230.1) and number of immunosuppressive medications (p=0.0015, CI 288.6 to 935.9).Of the 3 SJIA-LD patients who underwent BMT, we observed a higher BALF/plasma IL-18 ratio compared to other patients, although this was not significant (176±99 vs 34±16.5 (p=0.1)).For two SJIA-LD patients with serial samples, the changes of cytokine profile for one during disease flare-up and after therapeutic WLL are shown in Table 2, and before and after bone marrow transplant are in Table 3.

Conclusion: Patients with SJIA-LD showed a distinct BALF cytokine profile, with elevated IL-18, MMP-7, and CCL-11 but lower levels of other cytokines. These profiles also vary with flares and management, including WLL and BMT. Further prospective work is needed to determine the relationship with disease course and treatments.

IL-6 – interleukin 6, IL-8 – interleukin 8, IL-18 – interleukin 18, CCL-11 (Eotaxin-1) – C-C motif chemokine ligand 11, CCL17 (TARC) – C-C motif chemokine ligand 17, CCL25 – C-C motif chemokine ligand 25, MMP-7 – matrix metalloproteinase 7, CXCL9 – C-X-C motif chemokine ligand 9

*- group with a significantly higher level of marker compared to control overall and/or control subgroups (p < 0.05)

** – significantly higher level compared to non-inflammatory control group (p < 0.0001)

^ – significantly higher level compared to the main group (p < 0.05)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/analysis-of-bronchoalveolar-fluid-cytokine-profile-as-a-way-to-understand-the-lung-disease-associated-with-systemic-juvenile-idiopathic-arthritis/