Certain elevated biomarkers aid in diagnosis of systemic sclerosis-related ILD
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Key takeaways:
- Three biomarkers elevated in blood and/or bronchoalveolar lavage fluid were identified in patients with systemic sclerosis-related ILD.
- Several biomarkers observed in this review need more evidence.
For diagnosing systemic sclerosis-related ILD, Krebs von den Lungen-6, surfactant protein-D and interleukin-8 in blood/bronchoalveolar lavage fluid samples were found to be “reliable biomarkers,” according to results published in Thorax.
“Systemic sclerosis (SSc) is a rare but severe auto-immune disease that is poorly understood,” Bettina C. Schock, PhD, lecturer at The Wellcome-Wolfson Institute for Experimental Medicine at Queen’s University Belfast, told Healio. “As a complication, approximately 30% to 40% of patients develop clinically significant lung fibrosis (SSc-ILD) and of these, 40% die within 10 years of diagnosis.”
In a systematic review and meta-analysis, Schock and colleagues analyzed 38 studies — 36 observational and two investigational — published from January 2000 to September 2021 with a focus on biomarkers in peripheral blood or bronchoalveolar lavage fluid (BALF) samples from adults with SSc-ILD to find evidence of reliable markers in these samples that support a SSc-ILD diagnosis. All included studies evaluated patients with SSc-ILD against patients identified as healthy.
Through a 10-point checklist conducted in qualitative review, researchers concluded that the selected studies had an overall low risk for bias.
In the review, Schock and colleagues found 43 significant mediators in peripheral blood samples and 15 in BALF samples. Compared with control patients, patients with SSc-ILD had elevated levels of 38 markers in blood samples. Additionally, patients with SSc-ILD had higher levels of all 15 BALF mediators than controls; however, 14 of these markers only appeared in one study.
When assessing blood and BALF together for similar biomarkers, researchers observed increased measures of CCL2, interleukin (IL)-8, IL-10, human epididymis protein (HE4), alpha-defensin (HNP1) and MMP-9.
Biomarkers Krebs von den Lungen-6 (KL-6; 8 studies), surfactant protein-D (SP-D; 6 studies) and IL-8 (3 studies) were assessed in meta-analysis since they each appeared in more than two studies, narrowing down the total number of studies to 13 for this analysis.
For blood IL-8 levels, researchers looked at three studies (87 patients with SSc-ILD; 124 control patients), and for BALF IL-8 levels, they factored in two additional independent studies (55 patients with SSc-ILD; 15 controls).
In both peripheral blood and BALF samples, researchers found a relationship between higher IL-8 levels and SSc-ILD (overall standardized mean difference [SMD], 0.88; 95% CI, 0.61-1.15). They also assessed estimates of blood and BALF separately and observed comparable SMD (blood, 0.87; 95% CI, 0.43-1.3; BALF, 0.75; 95% CI, 0.16-1.34).
After excluding two studies in sensitivity analysis, researchers found no shift in the direction of the estimate or in heterogeneity (I2 = 0%).
For SP-D, researchers evaluated peripheral blood data from 154 patients with SSc-ILD and 198 control patients and found that patients with SSc-ILD had increased SP-D levels (SMD, 1.91; 95% CI, 1.41-2.41) than controls. By excluding one study, the heterogeneity of 66% from the main analysis went down to 0% and no change was found in the direction of the estimate.
Lastly, among the KL-6 blood data from 331 patients with SSc-ILD and 189 control patients, researchers found higher KL-6 in patients with SSc-ILD (SMD, 1.66; 95% CI, 1.17-2.14). By excluding one study that contributed to the high heterogeneity in the main analysis (74%), heterogeneity went down to 0% and the estimate remained in the same direction.
“Our subsequent meta-analysis provided robust evidence that high IL-8 in blood and BALF, and higher blood SP-D and KL-6 were associated with SSc-ILD, supporting earlier disease management suggestions and potential theranostics,” Schock told Healio.
“These results and additional mediators described in blood and BALF provide us with an excellent starting point to perform further studies to monitor disease progression in patients with SSc and to investigate novel pharmacological targets for SSc-ILD,” Schock added. “The everyday clinician will then have new tools to monitor disease progression and pharmaceutical intervention, ultimately helping this group of patients.”
For more information:
Bettina C. Schock, can be reached at b.schock@qub.ac.uk.