Inclusion Criteria:
Participants must meet all the following criteria to be eligible for enrollment:
1. Age: ≥ 5 years old.
2. Diagnosis: Diagnosed with systemic lupus erythematosus (SLE) based on the 2019 EULAR/ACR classification criteria.
3. Positive Antibody: At least one of the following antibodies positive within 12 months before screening or during the screening period:
* Antinuclear antibody (ANA) ≥ 1:80.
* Anti-double-stranded DNA (anti-dsDNA) antibody above the upper limit of normal (ULN).
* Anti-Smith (Anti-Sm) antibody above the ULN.
4. Treatment Resistance: Inadequate response to at least three of the following:
* Oral corticosteroids (OCS),
* Antimalarials,
* Conventional immunosuppressants (e.g., cyclophosphamide, mycophenolate mofetil, azathioprine, methotrexate, cyclosporine, tacrolimus, sirolimus, leflunomide),
* Biologics (e.g., TULIP-2, belimumab, rituximab). At least one treatment must involve immunosuppressants or biologics.
5. SLEDAI-2000 Score: ≥ 6 based on the SLEDAI-2000 scoring system.
6. Stable Standard Treatment: Currently receiving one or more of the following treatments at a stable dose:
* OCS (e.g., prednisone acetate or equivalent) at a stable dose for ≥7 days prior to initiation;
* Antimalarials: Dose stable for at least 7 days prior to the first dose.
* Conventional immunosuppressants: Stable dose for at least 4 weeks before screening and throughout the study.
7. Laboratory Parameters:
* Absolute lymphocyte count (ALC) ≥ 0.5 × 10⁹/L.
* Peripheral CD19+ B cell count ≥ 25 cells/μL.
* Absolute neutrophil count (ANC) ≥ 0.5 × 10⁹/L.
* Hemoglobin ≥ 80 g/L.
* Platelet count ≥ 75 × 10⁹/L \*.
* Left ventricular ejection fraction (LVEF) ≥ 55% with no significant ECG abnormalities.
* Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m².
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN; total bilirubin ≤ 2 × ULN.
* No severe pulmonary lesions, SpO₂ ≥ 92%.
8. Contraception: Female participants of childbearing potential must have a negative urine pregnancy test and agree to use effective contraception during the study and for 1 year after infusion.
9. Informed Consent: The participant and their legal guardian must provide written informed consent, demonstrating understanding of the study objectives and willingness.
* Note: For SLE patients with thrombocytopenia below the inclusion threshold due to immune-related causes, and without active bleeding, investigators may use clinical discretion to determine eligibility.
Exclusion Criteria:
Participants meeting any of the following criteria will be excluded:
1. Central nervous system disease: active or unstable lupus-related neuropsychiatric disease within 60 days, including epilepsy, confusion, cerebrovascular events, etc.;
2. Acute severe nephritis: renal replacement therapy within 3 months before the screening period or ongoing, or significant kidney disease that, in the opinion of the investigator, may occur and lead to the need for high-dose glucocorticoid (prednisone dose ≥ 2 mg/kg/d or equivalent of other hormones), cyclophosphamide or escalated MMF treatment within the first 3 months of the study;
3. Severe antiphospholipid syndrome within 12 months before or during screening；
4. Congenital heart disease or a history of acute myocardial infarction within 6 months before screening, or severe arrhythmia (including polymorphic ventricular tachycardia, ventricular tachycardia, etc.); or combined with moderate to large pericardial effusion, severe myocarditis, etc.; or unstable vital signs, patients who need blood pressure-raising drugs to maintain blood pressure;
5. Suffering from other diseases that require long-term administration of glucocorticoids or immunosuppressive agents;
6. Having active infections or uncontrollable infections that require systemic treatment within one week before screening;
7. Having received solid organ transplantation or hematopoietic stem cell transplantation within three months before screening; or having grade 2 or higher acute graft-versus-host disease (GVHD) within two weeks before screening;
8. History of severe recurrent or chronic infections, especially recurrent or chronic infections associated with respiratory problems.
9. Immunoglobulin G levels below the lower limit (5-8 years: \<4.5 g/L, 9 years and older: \<6.0 g/L);
10. History of hepatitis B virus (HBV) infection or positive serology indicating current or past HBV infection. Human immunodeficiency virus (HIV; positive HIV antibody test) and active hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid \[RNA\]). Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection;
11. A history of tuberculosis or active tuberculosis; or latent tuberculosis treated before the baseline; or subjects with an indeterminate test result who screened positive for PPD or T-spot can be retested, but if the repeat test is also indeterminate, they are excluded;
12. Had a history of macrophage activation syndrome within 1 month prior to screening;
13. Had received any anti-CD19 or anti-CD20 therapy, such as rituximab, obinutuzumab, ocrelizumab, or ofatumumab, within 3 months prior to screening or during screening;
14. Received a JAK inhibitor, Bruton tyrosine kinase (BTK) inhibitor, or tyrosine kinase 2 (TYK2) inhibitor, such as baricitinib, tofacitinib, upadacitinib, filgotinib, ibrutinib, or zanubrutinib and Fenebrutinib, during screening;
15. Treatment with cyclophosphamide or a biologic agent within 4 weeks prior to enrollment, including but not limited to adalimumab, etanercept, golimumab, infliximab, Infliximab), Belimumab, Ustekinumab, Anifrolumab, Secukinumab, or Atacicept;
16. Intolerance or contraindication to the investigational therapy, including a history of severe allergies or allergic reactions to monoclonal antibodies, or a known hypersensitivity to any of the ingredients in belimumab injection;
17. Live vaccine within 4 weeks prior to screening;
18. Positive blood pregnancy test;
19. Patients with known malignant diseases such as tumors before screening;
20. Patients who have participated in other clinical trials within 3 months prior to enrollment;
21. Patients with depression or suicidal tendencies;
22. Other situations where the investigator believes the patient is not suitable for participation in the study.
