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Changes in lung immune cells related to clinical outcome during treatment with infliximab for sarcoidosis
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  • Susanna Kullberg,
  • Natalia Rivera,
  • Muntasir Abo Al Hayja,
  • Johan Grunewald,
  • Anders Eklund
Susanna Kullberg
Karolinska University Hospital
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Natalia Rivera
Karolinska Institutet
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Muntasir Abo Al Hayja
Karolinska Institutet
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Johan Grunewald
Karolinska University Hospital
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Anders Eklund
Karolinska University Hospital
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Abstract

Background: Pulmonary sarcoidosis is characterized by an exaggerated CD4+ T-cell response and formation of non-necrotizing granulomas. Tumour necrosis factor α (TNF-α) is regarded as crucial for granuloma formation and TNF-α inhibitors offer a 3rd line treatment option for patients not responding to conventional treatment. However, not all patients benefit from treatment, and an optimal dose and treatment duration have not been established. Insight into the influence of TNF-α inhibitors on lung immune cells may provide clues to what drives inflammation in sarcoidosis and improve our understanding of treatment outcomes. Objectives: To evaluate effects of treatment with the TNF- α inhibitor infliximab on lung immune cells and clinical features of the patients. Methods: Thirteen patients with sarcoidosis refractory to conventional treatment were assessed with bronchoalveolar lavage (BAL), spirometry and CT scan in close adjacent to start of infliximab treatment. These investigations were repeated after six months of treatment. Results: Treatment with TNF- α inhibitor infliximab was well tolerated with no adverse events, except for one patient who developed a probable adverse event with liver toxicity. Ten patients were classified as responders, having a reduced CD4/CD8 ratio, a decreased percentage of CD4+ T-cells expressing the activation marker CD69 and number of mast cells (p<0.05 for all). The percentage of T regulatory cells (Tregs), defined as FoxP3+ CD4+ T-cells decreased in most patients. Conclusions: Six months of infliximab treatment in patients with sarcoidosis led to signs of decreased CD4+ T-cell alveolitis and decreased mastocytosis in the lungs of responders.

Peer review status:ACCEPTED

03 Mar 2020Submitted to Clinical & Experimental Immunology
04 Mar 2020Submission Checks Completed
04 Mar 2020Assigned to Editor
06 Mar 2020Reviewer(s) Assigned
17 Mar 2020Review(s) Completed, Editorial Evaluation Pending
17 Mar 2020Editorial Decision: Revise Major
25 Mar 20201st Revision Received
26 Mar 2020Reviewer(s) Assigned
30 Mar 2020Review(s) Completed, Editorial Evaluation Pending
30 Mar 2020Editorial Decision: Accept