Artikel
Urinary CD4+T-helper cells are a potential biomarker for renal involvement in Sjögren Syndrome
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Autoren
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Simon Melderis
- University Medical Center Hamburg-Eppendorf, III, Department of Medicine, Hamburg; Hamburg Center for Kidney Health, Hamburg
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Oliver M. Steinmetz
- University Medical Center Hamburg-Eppendorf, III, Department of Medicine, Hamburg; Hamburg Center for Kidney Health, Hamburg
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Laura-Isabell Ehnold
- University Medical Center Hamburg-Eppendorf, III, Department of Medicine, Hamburg; Hamburg Center for Kidney Health, Hamburg
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Viona Laas
- University Medical Center Hamburg-Eppendorf, III, Department of Medicine, Hamburg; Hamburg Center for Kidney Health, Hamburg
| Veröffentlicht: | 30. August 2023 |
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Gliederung
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Introduction: Kidney involvement in Sjögren Syndrome (SjS), usually in the form of interstitial nephritis (IN), causes significant morbidity and mortality. Repeat kidney biopsies are currently the gold standard for diagnosis and monitoring of treatment response, since non-invasive biomarkers are completely lacking. Our aim was thus to evaluate the specific cellular composition of urinary leukocytes as a potential marker for diagnosis and disease activity during follow up.
Methods: We established a multicolor flow cytometry (FC) panel to measure and differentiate urinary leukocyte populations. FC of fresh urinary leukocytes was performed in a collective of SjS-patients from our outpatient department with biopsy proven IN (SjS-IN) at the time of diagnosis versus healthy controls (HC). To further substantiate our approach, leukocyturia was longitudinally followed up for 240 days in a selected SJS-IN patient. In addition, treatment effects on leukocyturia were quantified in a collective of SjS-IN patients at the time of remission. Results from urinary FC were compared to standard laboratory parameters such as serum creatinine (SC), proteinuria (uPCR) and rheumatoid factor (RF).
Results: Eight different leukocyte populations could be identified in 13 HC and 9 SjS-IN patients. Of these, urinary CD4+ T-helper cells (uCD4+Th) were best able to differentiate between the groups. Both, relative and absolute numbers of uCD4+Th were significantly increased in SiS-IN. The abundance of other urinary leukocyte subtypes did not differ between the groups. In the longitudinal analysis of a selected patient, uCD4+Th were present at low levels, 200 days before establishing the diagnosis of SjS-IN. A significant rise was observed over time, simultaneously with worsening renal function (SC & uPCR) and rise in serological markers (RF). Following induction therapy with prednisolone and mycophenolat mofetil (MMF), a rapid and profound reduction in uCD4+Th could be seen, which preceded the fall in SC, uPCR and RF. In line with this observation, a cohort of 5 patients with biopsy proven SjS-IN showed a significant reduction in uCD4+Th after successful induction of remission.
Conclusion: 1) CD4+Th might be of pathophysiological relevance in SJS-IN. 2) Urinary CD4+Th are a potential non-invasive biomarker for renal disease activity.
Disclosure: No conflics of interest.
