An Clinical Study of YTS109 Cell Injection in Subjects With Recurrent/Refractory Autoimmune Disease

Inclusion Criteria:

1. Age ranges from 18 to 65 years old (including threshold), regardless of gender.

2. Positive expression of CD19 on peripheral blood B cells determined by flowcytometry.

3. The functions of important organs meet the following requirements:

4. Bone marrow hematopoietic function needs to meet: Neutrophil count ≥1×109/L;Hemoglobin ≥60g/L;

5. Liver function: ALT≤3×ULN; AST≤3×ULN; TBIL≤1.5×ULN;

6. Renal function: creatinine clearance (CrCl) ≥30 ml/minute;

7. Coagulation function: International standardized ratio (INR) ≤1.5×ULN,prothrombin time (PT) ≤1.5×ULN;

8. Heart function: good hemodynamic stability;

9. Female subjects with fertility and male subjects whose partners are women ofchildbearing age are required to use medically approved contraception or abstinenceduring the study treatment period and at least 6 months after the end ofthe studytreatment period; Female subjects of childbearing age tested negative for serum HCGwithin 7 days before enrollment in the study and were not in lactation.

10. Voluntarily participate in this clinical study, sign an informed consent form, havegood compliance, and cooperate with follow-up.

Specific inclusion criteria:

Recurrent refractory systemic lupus erythematosus

1. Complies with the classification standards of the 2019 European Union AgainstRheumatology/American Society of Rheumatology (EULAR/ACR) SLE;

2. Disease activity score SELENA SLEDAI≥6 with at least one Injima Lupus AssessmentGroup Index (BILAG-2004) category A (severe presentation) or two Category B (moderate presentation) organ scores, or both; Or disease activity score SELENASLEDAI score ≥8;

3. Definition of relapse refractory: conventional treatment remains ineffective formore than 6 months or disease activity occurs again after remission. Conventionaltreatment is defined as the use of glucocorticoids and cyclophosphamide, and any ofthe following immunomodulators: antimalarials, azathioprine, mortemycophanate,methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics includingrituximab, belimumab and telitacicept.

Recurrent refractory sjogren's syndrome

1. Meet the 2002 AECG criteria for primary Sjogren's syndrome or the 2016 ACR/EULARclassification criteria;

2. Disease activity ESSDAI≥6;

3. Positive anti-SSA /Ro antibody;

4. Definition of relapse refractory: conventional treatment remains ineffective formore than 6 months or disease activity occurs again after remission. Conventionaltreatment is defined as the use of glucocorticoids and cyclophosphamide, and any ofthe following immunomodulators: antimalarials, azathioprine, mortemycophanate,methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics includingrituximab, belimumab and telitacicept.

Relapsing refractory/progressive diffuse systemic sclerosis

1. Meet the 2013 ACR classification criteria for systemic sclerosis;

2. Positive antibodies related to systemic sclerosis;

3. Diffuse sclerosis of the skin or active interstitial pneumonia (HRCT suggests groundglass exudation);

4. Definition of relapse refractory: conventional treatment remains ineffective formore than 6 months or disease activity occurs again after remission. Conventionaltreatment is defined as the use of glucocorticoids and cyclophosphamide, and any ofthe following immunomodulators: antimalarials, azathioprine, mortemycophanate,methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics includingrituximab, belimumab and telitacicept

5. Definition of progression: rapid skin progression (mRSS increase >25%); Orprogression of lung disease (a 10% reduction in FVC, or a more than 5% reduction inFVC with a 15% reduction in DLCO).

6. Note: Articles 4 and 5 satisfy one or the other.

Recurrent refractory/progressive inflammatory myopathy:

1. Meet the 2017 EULAR/ACR classification criteria for inflammatory myopathy (includingDM, PM, ASS and NM);

2. Positive myositis antibody;

3. Patients with muscle involvement had an MMT-8 score of less than 142 and abnormalfindings on at least two of the following five core measures (PhGA, PtGA,extra-muscular disease activity score ≥2; HAQ total score ≥0.25; Muscle enzymelevels were 1.5 times the upper limit of the normal range); Or MMT-8≥142 with activeinterstitial lung disease (HRCT suggests ground glass exudation);

4. Definition of relapse refractory: conventional treatment remains ineffective formore than 6 months or disease activity occurs again after remission. Conventionaltreatment is defined as the use of glucocorticoids and cyclophosphamide, and any ofthe following immunomodulators: antimalarials, azathioprine, mortemycophanate,methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics includingrituximab, belimumab and telitacicept

5. Definition of progressive: myositis aggravation or rapid progression of interstitialpneumonia.

Note: Clauses 4 and 5 satisfy one or the other.

Recurrent/refractory ANCA-associated vasculitis:

1. Meet the 2022ACR/EULAR diagnostic criteria for ANCA vasculitis, includingmicroscopic polyvasculitis, granulomatous polyvasculitis, and eosinophilicgranulomatous polyvasculitis.

2. Anca-associated antibody positive (MPO-ANCA or PR3-ANCA positive);

3. Birmingham vasculitis activity score (BVAS) ≥15 points (total 63 points), indicatingvasculitis disease activity;

4. Definition of relapse refractory: conventional treatment remains ineffective formore than 6 months or disease activity occurs again after remission. Conventionaltreatment is defined as the use of glucocorticoids and cyclophosphamide, and any ofthe following immunomodulators: antimalarials, azathioprine, mortemycophanate,methotrexate, leflunomide, tacrolimus, cyclosporine, and biologics includingrituximab, belimumab and telitacicept.

Recurrent refractory/catastrophic antiphospholipid syndrome:

1. Meet the diagnostic criteria for primary antiphospholipid syndrome as revised inSydney 2006;

2. Positive titers of phospholipid antibodies (IgG/IgM of LA, B2GP1 or acL, more thantwo positive tests within 12 weeks);

3. Definition of relapse resistance: standard therapy with warfarin anticoagulant orreplacement vitamin K antagonists (i.e., maintenance of the INR required fortreatment) or with standard therapeutic dose of low molecular weight heparin (LMWH),as well as treatment of recurrent thrombosis with past hormones andcyclophosphamide;

4. Catastrophic antiphospholipid syndrome needs to meet the following four criteria: (1) involvement of three or more organs, systems and/or tissues; (2) Symptoms appearwithin 1 week; (3) Histologically confirmed obstruction of small blood vessels in atleast one organ or tissue; (4) aPL was positive.

Note: Clauses 3 and 4 satisfy one or the other.

Exclusion Criteria:

1. People with severe drug allergy or allergic constitution;

2. the presence or suspicion of fungal, bacterial, viral or other infections thatcannot be controlled or require treatment;

3. Subjects with central nervous system disorders (excluding pre-existing epilepsy,psychosis, organic encephalopathy syndrome, cerebrovascular accident, encephalitis,central nervous system vasculitis as a result of the disease);

4. Patients with cardiac dysfunction;

5. Subjects with congenital immunoglobulin deficiency;

6. History of malignant tumor in recent five years;

7. Subjects with end-stage renal failure;

8. Subjects with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb)positive and peripheral blood HBV DNA titer higher than the upper limit ofdetection; Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNApositive; Human immunodeficiency virus (HIV) antibody positive; Syphilis positive;

9. Mental illness and severe cognitive impairment;

10. Participants who had participated in other clinical trials within 3 months beforeenrollment;

11. The duration of use of immunosuppressants that have therapeutic effects on thedisease before enrollment was within five half-lives or biologics within four weeks;

12. A woman who is pregnant or planning to become pregnant;

13. The investigators believe that there are also subjects who could not be included inthe study for other reasons.