Background/Purpose: Both traumatic injury/hemorrhagic shock (T/HS) and rheumatoid arthritis (RA) are inflammatory diseases that are major sources of morbidity worldwide. We hypothesize that RA modifies T/HS-induced dynamic inflammatory networks, and that anti-inflammatory therapy for RA may modify T/HS-induced inflammation and outcomes. Accordingly, we sought to compare a prolonged time course of post-injury inflammatory mediators and outcomes in T/HS patients with or without RA.

Methods: From a cohort of 472 blunt trauma survivors studied following IRB approval, 12 patients diagnosed with seropositive RA according to 2010 ACR criteria (8 males and 4 females; age: 65±4; ISS: 17±1, receiving Methotrexate and tumor necrosis factor-a [TNF-a]-inhibitors) were matched with 12 non-RA control patients (8 males and 4 females; age: 68±4, ISS: 17±2).  Serial blood samples were obtained from all patients (3 samples within the first 24 h and then daily from days 1 to 7 post-injury). Twenty-three plasma inflammatory mediators were assayed using Luminex™, along with NO₂^–/NO₃^– assayed using nitrate reductase, respectively. Statistically significant differences (P < 0.05) between both groups were determined using the two-way analysis of variance (ANOVA) followed by the Holm-Sidak post hoc test. In silico Dynamic Bayesian Network (DBN) inference was utilized to infer causal relationships among inflammatory mediators based on probabilistic measures. Human genomic DNA was isolated and amplified for known TNF-α, IL-6, IL-10, and IFN-γ single nucleotide polymorphisms (SNPs) using PCR, along with TLR4 (Asp299Gly and Thr300I1e) SNPs using gel-DNA sequencing.

Results: There was no statistical difference in the ICU length of stay, total length of stay, days on mechanical ventilation, and Marshall score (a measure of organ dysfunction) in RA vs. non-RA patients. Plasma levels of TNF-α, IL-6, IL-10, IL-17, MIG, MIP-1β, and NO₂^–/NO₃^–were significantly elevated within the 24 h in the RA group and up to day 7 when compared to the non-RA group.  In contrast, plasma IP-10 and MCP-1 levels were significantly lower in the RA group within the first 24 h when compared to controls. DBN suggested that the inflammatory response in RA trauma patients is mainly driven by MIG, whereas MCP-1 drives the inflammatory response via forward-positive loops with IP-10 and MIG in non-RA patients. The incidence of all of the measured SNPs was not significantly different between trauma patients with or without RA.

Conclusion: To our knowledge, this is the first pilot study that characterizes the inflammatory response in RA patients following blunt trauma. Our analysis suggested that different cytokine patterns emerge, particularly in the early events post-injury, in RA patients independent of the injury severity score on admission. Network analysis points to MIG as a key driver of this process. Larger cohorts are needed to clarify the role that T/HS plays in RA disease activity and therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/dynamics-of-the-inflammatory-response-in-rheumatoid-arthritis-patients-following-traumatic-injury-insights-from-in-vivoin-silico-and-single-nucleotide-polymorphism-studies/