Date: Monday, November 8, 2021
Session Type: Abstract Session
Session Time: 4:15PM-4:30PM
Background/Purpose: Relapsing polychondritis (RP) is an inflammatory disorder that affects cartilage of ears, nose, joints, and respiratory tract. The inflammation often spreads to eyes, cardiovascular system, inner ears, skin, and CNS. Previous studies of RP disclosed that mononuclear cells migrated into the perichondral tissues and adjacent chondrocytes produced matrix metalloproteinase (MMP)-3. We found that serum MMP3 concentrations were significantly higher in RP patients, especially in patients with respiratory involvement, than healthy individuals (HI). In the current study, we investigate whether serum MMP3 associate with inflammatory cytokine mRNA expressions of peripheral blood mononuclear cells (PBMC) in RP patients with a focus on the incidence and severity of the complications.
Methods: We obtained sera and PBMC from 30 RP patients and age and gender matched 14 HI. We divided the patients into two subgroups, that is, those with airway involvement (respiratory subgroup, 16 patients) and those without airway involvement (non-respiratory subgroup, 14 patients). We measured mRNA expressions of IL1β, IL6, TNFα, and MMP3, in freshly isolated, 6-hour-cultured, and 24-hour-cultured PBMC. We collected time series data of serum MMP3 and cytokine gene expressions from 6 RP patients (follow-up, mean ± sem., 34 ± 7.0 months) and 6 HI (45 ± 0.2 months).
Results: Inflammatory cytokine mRNA expressions of freshly isolated PBMC were significantly lower in RP patients than those in HI. IL1β and MMP3 mRNA expressions of 24-hour-cultured PBMC were significantly higher in RP patients than those in HI. Serum MMP3 increased significantly in respiratory subgroup compared with those in non-respiratory subgroup. Serum MMP3 and mRNA expressions of IL1β and IL6 showed positive linear correlations in 6-hour- and 24-hour-cultured PBMC of respiratory subgroup, but not those in non-respiratory subgroup. Linear correlations were found between serum MMP3 and PBMC MMP3 mRNA in both respiratory and non-respiratory subgroups. A linear correlation was observed between serum MMP3 and RPDAI in non-respiratory subgroup but not in respiratory subgroup. The time series study suggests that serum MMP3 and IL1β mRNA expressions of 6-hour-cultured PBMC were higher in RP patients than those in HI at least for several years (39 ± 3.7 months).
Conclusion: It is possible that IL1β has a potential to induce efficiently immune responses of RP cartilaginous tissues in the airway tract using MMP3. RPDAI may be more sensitive for the evaluation of disease status in non-respiratory subgroup than that in respiratory subgroup. RP PBMC may have a characteristic for persisting their dysregulated immune responses for a long time.
To cite this abstract in AMA style:Shimizu J, Wakisaka S, Suzuki T, Suzuki N. IL1β mRNA Expressions in Peripheral Blood Mononuclear Cells Increase and May Associate with Cartilage Damage of the Respiratory Tract Probably Through Matrix metalloproteinase-3 Production in Patients with Relapsing Polychondritis [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/il1%ce%b2-mrna-expressions-in-peripheral-blood-mononuclear-cells-increase-and-may-associate-with-cartilage-damage-of-the-respiratory-tract-probably-through-matrix-metalloproteinase-3-production-in-pat/. Accessed September 25, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/il1%ce%b2-mrna-expressions-in-peripheral-blood-mononuclear-cells-increase-and-may-associate-with-cartilage-damage-of-the-respiratory-tract-probably-through-matrix-metalloproteinase-3-production-in-pat/