The effect of Rituximab on B cells in pediatric autoimmune rheumatic diseases

Objectives: This study examines how demographic factors and disease conditions affect B-cell depletion and regeneration after Rituximab (RTX) infusion in pediatric patients with rheumatic conditions.
Methods: We retrospectively reviewed 27 patients approved by the Institutional Review Board, all of whom received at least one RTX infusion, analyzing 99 lymphocyte subunits. Inclusion: patients under 18 at their first RTX infusion, diagnosed with pediatric rheumatologist-confirmed autoimmune diseases. B-cell depletion was defined as a CD19 positive B Cells (CD19+) count below 10 cells/μL, assessed at 6- and 12-months post-RTX infusion. Complete regeneration was defined as CD19+ ≥170 cells/μL using adolescent norms.
Results: Most patients had connective tissue disorders (CTD); Systemic Lupus Erythematosus, Sjögren's Disease, Systemic Sclerosis; n=17; 63%), followed by vasculitis (n=5; 18.5%), juvenile dermatomyositis (n=4; 14.8%), and miscellaneous conditions (n=1; 3.7%). Among patients with CTD, 4 out of 12 (33%) had B-cell depletion at 6 months. At 12 months, 3 out of 6 (50%) achieved CD19+ counts ≥10 cells/μL, while 5 out of 6 (83%) did not reach normal levels of CD19+ (≥170 cells/μL). No significant correlation existed between immunosuppressants (mycophenolate mofetil, methotrexate, azathioprine, cyclosporine, cyclophosphamide) and CD19+≥10 cells/μL at 6 or 12 months. However, hydroxychloroquine significantly differed for persistent depletion at 12 months.
Conclusion: This study demonstrates that demographic factors and disease conditions influence B-cell depletion and regeneration in pediatric patients treated with RTX for rheumatic conditions. The findings highlight the variability in response to RTX and suggest that factors such as hydroxychloroquine use may impact long-term B-cell levels.

Rituximab'ýn pediatrik otoimmün romatizmal hastalýklarda B hücreleri üzerindeki etkisi

Amaçlar: Bu çalýþma, romatizmal rahatsýzlýðý olan pediatrik hastalarda Rituksimab (RTX) infüzyonu sonrasý demografik faktörlerin ve hastalýk koþullarýnýn B hücresi tükenmesini ve rejenerasyonunu nasýl etkilediðini incelemektedir.
Yöntemler: Kurumsal Ýnceleme Kurulu tarafýndan onaylanan ve en az bir RTX infüzyonu yapýlan 27 hastayý retrospektif olarak inceledik ve 99 lenfosit alt birimini analiz ettik. Dahil edilen: Pediatrik romatolog tarafýndan doðrulanmýþ otoimmün hastalýklar teþhisi konan ilk RTX infüzyonunda 18 yaþýn altýndaki hastalar. B hücresi tükenmesi, RTX infüzyonundan 6 ve 12 ay sonra deðerlendirilen 10 hücre / µl'nin altýnda bir CD19 pozitif B Hücresi (CD19 +) sayýsý olarak tanýmlandý. Tam rejenerasyon, adolesan normlarý kullanýlarak CD19+ ≥170 hücre/ µL olarak tanýmlandý.
Bulgular: Hastalarýn çoðunda bað dokusu bozukluklarý (BDB); Sistemik Lupus Eritematozus, Sjögren Hastalýðý, Sistemik Skleroz; n=17;% 63), ardýndan vaskülit (n=5;% 18.5), juvenil dermatomiyozit (n=4;% 14.8) ve çeþitli durumlar (n=1; 3.7%). CTD içinde 12'sinden 4'ü (% 33) 6 ayda tükendi. 12 Ayda 6'nýn 3'ü (% 50) CD19 + ≥10 hücre / µL gösterirken, 6'nýn 5'i (% 83) normal CD19 + seviyelerine (≥170 hücre / µL) ulaþmadý. Ýmmünosupresanlar (mikofenolat mofetil, metotreksat, azatioprin, siklosporin, siklofosfamid) ile 6 veya 12 ayda CD19 + ≥10 hücre / µL arasýnda anlamlý bir iliþki yoktu. Bununla birlikte, hidroksiklorokin, 12 ayda kalýcý tükenme için önemli ölçüde farklýydý.
Sonuç: Bu çalýþma, romatizmal tanýlarla RTX ile tedavi edilen pediatrik hastalarda demografik faktörlerin ve hastalýk koþullarýnýn B hücresi tükenmesini ve yenilenmesini etkilediðini göstermektedir. Bulgular, RTX'e yanýttaki deðiþkenliði vurgulamaktadýr ve hidroksiklorokin kullanýmý gibi faktörlerin uzun vadeli B hücresi seviyelerini etkileyebileceðini göstermektedir. (NCI-2024-7-9)