Kittikorn Wangriatisak1, Chokchai Thanadetsuntorn2, Thamonwan Krittayapoositpot1, Chaniya Leepiyasakulchai1, Thanitta Suangtamai2, Pintip Ngamjanyaporn2, Ladawan Khowawisetsut3,4, Prasong Khaenam5, Chavachol Setthaudom6, Prapaporn Pisitkun7,8, Patchanee Chootong9. 1. Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, 999 Phutthamonthon Sai 4 Road, Salaya, Nakhonpathom, 73170, Thailand. 2. Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road, Ratchathewi, Bangkok, 10400, Thailand. 3. Department of Parasitology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 4. Center of Excellence for Microparticle and Exosome in Diseases, Department of Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 5. Center of Standardization and Product Validation, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand. 6. Immunology Laboratory, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 7. Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road, Ratchathewi, Bangkok, 10400, Thailand. prapaporn.pis@mahidol.ac.th. 8. Translational Medicine Program, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. prapaporn.pis@mahidol.ac.th. 9. Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, 999 Phutthamonthon Sai 4 Road, Salaya, Nakhonpathom, 73170, Thailand. pchooton@gmail.com.
Abstract
BACKGROUND: Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. METHODS: Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients' peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. RESULTS: The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. CONCLUSION: Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.
BACKGROUND: Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. METHODS: Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLEpatients' peripheral blood. Clinical disease activities were assessed in SLEpatients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. RESULTS: The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLEpatients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. CONCLUSION: Our study demonstrated an expansion of aNAV B cells in SLEpatients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.
Entities:
Keywords:
Activated naïve B cell; DNA autoreactive B cell; Disease activity; Systemic lupus erythematosus
Authors: Carolina Hurtado; Diego Fernando Rojas-Gualdrón; Rodrigo Urrego; Kevin Cashman; Elsa María Vásquez-Trespalacios; Juan Camilo Díaz-Coronado; Mauricio Rojas; Scott Jenks; Gloria Vásquez; Ignacio Sanz Journal: Front Med (Lausanne) Date: 2022-09-06