CD19-BCMA CART Cell Therapy for Refractory SLE-LN, SSc, and pSS-PAH

This is a single-center, open-label, non-randomized, single-arm clinical trial. Patients with refractory lupus neritis (SLE-LN), systemic sclerosis (SSc), primary Sjogren syndrome combined with pulmonary artery hypertension (pSS-PAH) and other autoimmune diseases (AID) receive CD19-BCMA CAR T cell therapy. Phase I (Dose-Escalation/Dose-De-escalation Phase)：The primary objective is to prospectively assess the safety of CD19-BCMA CAR T cell therapy in patients with SLE-LN, SSc, pSS-PAH and other autoimmune diseases (AID).Phase I (Dose-Escalation/Dose-De-escalation Phase)：Primary Endpoint: Safety, tolerability, and determination of the optimal biological dose (OBD) and the Phase II recommended dose (RP2D) in patients with SLE-LN, SSc, pSS-PAH, and other autoimmune diseases (AID).Phase II (Dose-Expansion Phase):Overall remission rate (ORR) \[Time Frame: 90,180 Days\]

Inclusion Criteria 1. Refractory Lupus Nephritis（LN）: Patients who meet all the following requirements can be enrolled in the group. Definition: Failure to achieve induction remission after 3 to 6 months of treatment with at least one immunosuppressive agent (including glucocorticoids, cyclophosphamide \[CTX\], tacrolimus, mycophenolate mofetil, and cyclosporine), accompanied by no reduction (or worsening) in proteinuria or persistent positive autoantibodies. Diagnostic criteria : According to the 2019 American College of Rheumatology (ACR) criteria, and confirmed by renal biopsy in accordance with the 2018 International Society of Nephrology (ISN)/Renal Pathology Society (RPS) criteria (Appendix 3), were diagnosed with active, proliferative lupus nephritis (LN), including Class III or IV \[excluding Class III (C), IV-S (C), and IV-G (C)\], or combined Class III/IV with Class V. 1. Male or female, aged 10-65 years; 2. Meeting the 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria for Systemic Lupus Erythematosus (Appendix 4); 3. The ANA result is positive which means ANA titer≥ 1:80 (based on the equivalent detection results by Hep-2 immunofluorescence assay or enzyme immune assay), and/or according to the detection results from center laboratory, during the screening visit,the anti dsDNA serum antibody test is positive (based on ELISA assay, ≥30 IU/mL); 4. B cell CD19+ expression, and stop using immunosuppressant more than one week. 5. The lymphocyte count in the subject's blood routine \>0.5×109/L, and no contraindications for cell collection; 6. No serious allergic constitution; 7. ECOG score: 0-2: 8. Expected survival ≥90 days: Subjects and/or their guardian can understand and sign the informed consent form. 2\. SSc: Patients who meet all the following requirements can be enrolled in the group. 1. Patients or their legal representatives sign the informed consent form; 2. Male or female, aged 18-65 years. 3. According to the SSc classification criteria proposed by American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR), chose the highest score under the same condition. If the score ≥9, it can be classified SSc. (Appendix 5) 4. Satisfy a sufficient condition: the skin on the fingers of both hands is thickened and extend to the proximal end of metacarpophalangeal joint; 5. The lymphocyte count in the subject's blood routine \>0.5×109/L, and no contraindications for cell collection. 3\. pSS-PAH: Patients who meet all the following requirements can be enrolled in the group. 1. Patients or their legal representatives sign the informed consent form; 2. Male or female, aged 18-65 years; 3. Refractory connective tissue disease (PAH)patients: a) Satisfy the 2002 AECG or 2016 ACR/2016 EULAR classification criteria, can be diagnosed as pSS (Appendix 6); b) Confirmed by Right heart catheterization, satisfy the diagnose criteria of PAH: mPAP at rest ≥20mmHg; PAWP≤15mmHg; PVR at rest\>2WUs. 4. Low-risk patients whose PAH do not reach the risk stratification. The patients should meet: WHO cardiac function grading I-II; 6 minutes walking distance\>440 m; BNP\