Personalized medicine in sarcoidosis: unravelling biomarkers for targeted care

Francesqui, Joel; Marrades, Pau; Sellares, Jacobo

doi:10.1097/mcp.0000000000000985

Cited by 6 publications

(3 citation statements)

References 48 publications

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“…They include angiotensin-converting enzyme (ACE), soluble interleukin-2 receptor (sIL2R), chitotriosidase (CTO), neopterin, CCL18, hypercalcemia, and hypercalciuria. [56][57][58] The use of corticosteroids, however, is postulated to be a risk factor for sarcoidosis relapse. [28] The process of granuloma formation in sarcoidosis has been conjectured to play an important role in clearing the triggering antigen.…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Risk Factors of Relapse in Pulmonary Sarcoidosis: A Systematic Review and Meta-analysis

Hashim,

Tripathy,

Nath

et al. 2023

Preprint

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Background and Aim: Relapses in pulmonary sarcoidosis (PS) adversely affect the clinical management and prognosis of the disease, but there is a paucity of data on their incidence and risks. We aimed to systemically review and meta-analyze the available studies for evaluating the pooled weighted incidence and risk factors for relapse in the disease. Methods: We systematically searched electronic databases, including PubMed, Google Scholar, Scopus and Embase, and performed a manual search to collect eligible studies published until 31 October 2023. The prevalence and risk factors for relapse of PS were analyzed by a random effect model using proportions with 95% confidence intervals (CIs). Results: Of the 1402 records retrieved, 26 studies met the inclusion criteria. All these studies were from tertiary centers. Mean age of the relapse groups was 45.94 years (SD 10.87). The prevalence of relapse in sarcoidosis (843 relapses in 2698 sarcoidosis subjects) varied from 11–67%, with a pooled prevalence of 0.34 [95% CI, 0.28–0.40]. Relapses were more common in blacks than in white individuals [0.72 (0.65–0.79) vs [0.27 (0.20–0.34), p = 0.00]. There were no significant differences in subgroups based on age, sex, location, or type of study. Although not reaching statistically significance, the number of relapses were higher in the female as compared to males [Risk difference 0.05(95% CI: -0.01-0.11, p = 0.09)]. Conclusion: Our study shows a pooled incidence of PS relapse of 34%, suggesting a regular follow-up of the patients for early detection of relapse and improved prognosis of the disease.

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Section: Discussionmentioning

confidence: 99%

Prevalence and Risk Factors of Relapse in Pulmonary Sarcoidosis: A Systematic Review and Meta-analysis

Hashim,

Tripathy,

Nath

et al. 2023

Preprint

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“…Serum biomarkers are also potentially useful in treatment assessment [101]. Angiotensinconverting enzyme does modestly correlate with parenchymal burden in the lung.…”

Section: Biomarkers In the Management Of Therapymentioning

confidence: 99%

Treatment of Granulomatous Inflammation in Pulmonary Sarcoidosis

Gerke

2024

JCM

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The management of pulmonary sarcoidosis is a complex interplay of disease characteristics, the impact of medications, and patient preferences. Foremost, it is important to weigh the risk of anti-granulomatous treatment with the benefits of lung preservation and improvement in quality of life. Because of its high spontaneous resolution rate, pulmonary sarcoidosis should only be treated in cases of significant symptoms due to granulomatous inflammation, lung function decline, or substantial inflammation on imaging that can lead to irreversible fibrosis. The longstanding basis of treatment has historically been corticosteroid therapy for the control of granulomatous inflammation. However, several corticosteroid-sparing options have increasing evidence for use in refractory disease, inability to taper steroids to an acceptable dose, or in those with toxicity to corticosteroids. Treatment of sarcoidosis should be individualized for each patient due to the heterogeneity of the clinical course, comorbid conditions, response to therapy, and tolerance of medication side effects.

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“…Estimating the response to glucocorticoids can be challenging and prolonged prednisone use can have significant toxicity and side effects [ 2 – 4 ]. There is an unmet need to develop biomarkers that predict therapeutic response [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Increased proportions of circulating PD-1+ CD4+ memory T cells and PD-1+ regulatory T cells associate with good response to prednisone in pulmonary sarcoidosis

Miedema,

de Jong,

Kahlmann

et al. 2024

Respir Res

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Background The treatment response to corticosteroids in patients with sarcoidosis is highly variable. CD4+ T cells are central in sarcoid pathogenesis and their phenotype in peripheral blood (PB) associates with disease course. We hypothesized that the phenotype of circulating T cells in patients with sarcoidosis may correlate with the response to prednisone treatment. Therefore, we aimed to correlate frequencies and phenotypes of circulating T cells at baseline with the pulmonary function response at 3 and 12 months during prednisone treatment in patients with pulmonary sarcoidosis. Methods We used multi-color flow cytometry to quantify activation marker expression on PB T cell populations in 22 treatment-naïve patients and 21 healthy controls (HCs). Pulmonary function tests at baseline, 3 and 12 months were used to measure treatment effect. Results Patients with sarcoidosis showed an absolute forced vital capacity (FVC) increase of 14.2% predicted (± 10.6, p < 0.0001) between baseline and 3 months. Good response to prednisone (defined as absolute FVC increase of ≥ 10% predicted) was observed in 12 patients. CD4+ memory T cells and regulatory T cells from patients with sarcoidosis displayed an aberrant phenotype at baseline, compared to HCs. Good responders at 3 months had significantly increased baseline proportions of PD-1+CD4+ memory T cells and PD-1+ regulatory T cells, compared to poor responders and HCs. Moreover, decreased fractions of CD25+ cells and increased fractions of PD-1+ cells within the CD4+ memory T cell population correlated with ≥ 10% FVC increase at 12 months. During treatment, the aberrantly activated phenotype of memory and regulatory T cells reversed. Conclusions Increased proportions of circulating PD-1+CD4+ memory T cells and PD-1+ regulatory T cells and decreased proportions of CD25+CD4+ memory T cells associate with good FVC response to prednisone in pulmonary sarcoidosis, representing promising new blood biomarkers for prednisone efficacy. Trial registration NL44805.078.13

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Personalized medicine in sarcoidosis: unravelling biomarkers for targeted care

Cited by 6 publications

References 48 publications

Prevalence and Risk Factors of Relapse in Pulmonary Sarcoidosis: A Systematic Review and Meta-analysis

Prevalence and Risk Factors of Relapse in Pulmonary Sarcoidosis: A Systematic Review and Meta-analysis

Treatment of Granulomatous Inflammation in Pulmonary Sarcoidosis

Increased proportions of circulating PD-1+ CD4+ memory T cells and PD-1+ regulatory T cells associate with good response to prednisone in pulmonary sarcoidosis

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