case_images: PMC11825476_01
case_images: (A) CT scan before the thoracoscopic lung biopsy and steroid initiation, showing massive bilateral areas of airless lung tissue, more prominent in the lower lobes, located in both central and peripheral areas. (B) CT scan after 2 weeks of treatment with high doses of steroids.
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case_images: PMC11825476_01_fimmu-15-1523256-g001.jpg
case_images: f1
case_images: At the age of 27, respiratory failure occurred after another attempt at steroid cancelation, accompanied by subtotal lung damage observed on CT scans ( Figure 1A ). Optimal response was observed on high-steroid doses ( Figure 1B ) with slow de-escalation to low-dose regimen.
case_images: Assessment of phosphorylation of intracellular protein STAT1 after stimulation by IFNgamma in monocytes of the patient and healthy donor. The histogram displays the analysis of the STAT1 protein phosphorylation, with the stimulation time in minutes (15, 60, and 120 min) on the left and the mean fluorescence intensity on the right. The non-stimulated sample is noted as NON STIM, the red color shows the phosphorylation points of the patient before the therapy (A1), the blue color shows after 1 year of the JAK inhibitor therapy course (A2), and the gray color shows a control sample from a conditionally healthy person (B). To determine the kinetics of phosphorylation, we compared the fluorescence intensity of the samples stimulated during different time intervals with an unstimulated sample. The in-house references showed the enhanced phosphorylation of the STAT1 protein in the patient before therapy with a maximum value of 60 min. After the course of therapy, the result complied with the reference values and was comparable with the protein phosphorylation in a conditionally healthy person.
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case_images: PMC11825476_01_fimmu-15-1523256-g002.jpg
case_images: f2
case_images: In our case, the STAT1 phosphorylation assay also demonstrated hyperactivation of the STAT1 pathway ( Figure 2 ). Nevertheless, evaluation of STAT1 phosphorylation a year after JAK inhibitor initiation showed results comparable with protein phosphorylation in a conditionally healthy person ( Figure 2 ).
case_images: CT scans: (A) at the beginning of ruxolitinib treatment (started from the dose of 15 mg/day then escalated to 30 mg/day) and steroid tapering (from the dose of 12 mg/day of methylprednisolone to complete withdrawal); (B) after 3 months of ruxolitinib treatment and straight after complete steroid discontinuation; (C, D) 9 and 16 months since ruxolitinib initiation (which is 6 and 13 months of monotherapy with ruxolitinib correspondingly, 30 mg per day). (A, B) Reduced pneumatization of the lung tissue in the basal sections, with no dynamics in the areas of hypostatic changes between (C, D) improved pneumatization in the basal sections, with less prominent reticular changes. Shown below are the lung function tests in time correlation with CT scan performance. FVC, forced vital capacity; FEV1, forced expiratory volume in 1 s; VC, vital capacity; PEF, peak expiratory flow.
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case_images: PMC11825476_01_fimmu-15-1523256-g003.jpg
case_images: f3
case_images: Finally, the steroids were completely canceled after 3 months ( Figures 3A, B ). Pneumatization in the basal sections of the lungs was improved and reticular changes became less prominent ( Figure 3C ). At the 16-month checkpoint, all the symptoms were still under control ( Figure 3D ).