Biomarkers of interstitial lung disease associated with primary Sjögren's syndrome

Abstract

Objectives The aim of this study was to investigate serum biomarkers linked to primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD). Methods 69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs). Results Among consecutively enrolled patients with pSS, the presence of pSS–ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS–ILD group (ILA 2 + ILA 3) than in the pSS–no-ILD and pSS–indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p < 0.05 for all variables). A binary logistic regression model revealed that disease duration and KL-6 levels were associated with the presence of pSS–ILD (p < 0.05). Complementary least absolute shrinkage and selection operator (LASSO) modeling showed that age, KL-6, and TNF-α effectively differentiated pSS–ILD (ILA 2 + ILA3) from pSS without ILD (ILA 0 + ILA 1), with an area under the curve (AUC) of 0.883 (p value < 0.0001). Conclusions Patient age, disease duration, and serum levels of both KL-6 and TNFα were the most discriminating factors associated with the presence of ILD in our pSS patients. Higher levels of CRP, IgM, eotaxin, TGFα, and TNFα should also prompt the search for occult as well as clinically evident lung involvement based on statistically significant univariate associations with pSS–ILD. Clinical trial registration None.

Interstitial Lung Disease and Pulmonary Damage in Primary Sjögren’s Syndrome: A Systematic Review and Meta-Analysis

“…Eleven studies had a prospective design, and among them four were conducted in Greece [ 17 , 18 , 19 , 20 ], three in Sweden [ 21 , 22 , 23 ], one in Spain [ 24 ], one in the Netherlands [ 25 ], two in Italy [ 26 , 27 ], and one in China [ 28 ]. Nineteen studies had a retrospective design, and among them ten were conducted in China [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ], three in Turkey [ 38 , 39 , 40 ], two in France [ 41 , 42 ], one in Italy [ 26 ], one in the Netherlands [ 43 ], one in Japan [ 44 ], one in Spain [ 45 ], and one in Germany [ 46 ]. Many of them referred to pSS patients fulfilling the revised criteria proposed by the American–European Consensus Group [ 47 ].…”

“…Many of them referred to pSS patients fulfilling the revised criteria proposed by the American–European Consensus Group [ 47 ]. In 23 studies out of the 30 included HRCT was performed to investigate lung involvement [ 19 , 20 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. The main characteristics of the selected studies are reported in Table 1 .…”

“…By this strategy, our results show a pooled pSS-ILD prevalence of 23% (95% CI: 16–30), which is higher than the prevalence reported in another study, which showed a pooled prevalence of 13% (95% CI: 9–19) [ 49 ]. Compared to this previous meta-analysis, performed more than 5 years ago, we found nine new papers published in recent years exploring the pSS-ILD prevalence [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 45 , 46 ]. These data confirm, on one hand, that pSS-ILD is an emerging hot topic, and on the other hand the need for “refreshing” previous metanalyses considering the relatively fast increase of knowledge in the field of autoimmune diseases.…”

“… Forest plots depicting the pooled prevalence estimate for ILD in Sjogren patients with subgroup analyses for HRCT. Diamonds indicate the overall summary estimates, and width of the diamonds represents the 95% confidence interval (CI); boxes indicate the weight of individual studies in the pooled results [ 17 , 18 , 19 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. …”

Immune-mediated lung diseases: A narrative review

“…Patients with SS can manifest significant BAL lymphocytosis, but this was not proven to be an early sign of severe lung fibrosis (70). Type II pneumocytes in patients with ILD produce a mucin-like glycoprotein called KL-6 (71). The serum level of KL-6 correlates significantly with ILD prognosis and disease severity as defined by HRCT and is considered a potentially useful diagnostic marker for detecting asymptomatic SS-ILD patients (71)(72)(73).…”