Lupus nephritislnIt is one of the manifestations of severe organ damage in systemic lupus erythematosus (SLE), and an important cause of disability and death, and its pathogenesis is related to immune abnormalities such as immune cells, cytokines, and immune complex deposition. In recent decades, scholars have conducted a number of clinical trials using mesenchymal stem cells (MSCs) for the most refractory autoimmune diseases, including SLE, with encouraging results.
Amin et al. published a clinical trial on LN in Current Research in Translational Medicine, which showed that the study used MSCS of allogeneic fat**, and the disease activity score of patients was greatly improved 6 months after transplantation.
The phase I clinical trial included a total of 9 adult patients (8 females and 1 male) with refractory LN, aged 19 to 36 years and with a disease duration of 3 to 12 years. According to the ISN RPS classification, the LN grade of the patients was as follows: 3 cases of IV-S(A C), 3 cases of IV-G(A C), 2 cases of IV-G(A), and 1 case of grade III(A).
Transplantation protocol:Prior to MSCS infusion, patients received 10 mg of chlorpheniramine maleate and 200 mg of hydrocortisone intravenously, and 500 mg of acetaminophen orally to control potential allergic and febrile reactions, followed by an intravenous infusion of 2 million kg of AD-MSCs (all donors were siblings).
Results: Changes in urine protein:One week after the intervention, the urine protein level decreased significantly;At 1 month, this parameter reached the lowest record;At the following follow-up, the urine protein level gradually increased, but this parameter was still significantly lower than baseline;At the last 2 follow-ups, the median 24-hour proteinuria was consistently below baseline (Figure 2).
Post-transplant reactions:1 week after transplantation, 3 patients (33.)3% had a complete response (CR), and 3 patients (33.)3%);One month after transplantation, the cumulative incidence of PR increased to 444%, the CR rate remains the same;From the 3rd month to the end of our assessment, the PR and CR rates gradually decreased to 111% (Figure 3).
SLE Disease Activity Index 2000 (sledai-2kAt 1 week post-transplant, sledai-2k was 10 (8-16);At 1 month, sledai-2k was 8 (2 12);At 3 months, sledai-2k was 6 (2 16);At 6 months, sledai-2k was 6(0 12);At 12 months, there was a slight increase of SLEDAI-2K to 8 compared to the previous visit, but it was still significantly below baseline (16 for SLEDAI-2K), as shown in Table 1.
Glomerular filtration rate (EGFR).Seven patients were found to have abnormal EGFR at baseline, and this parameter improved significantly within 3 months after MSCS transplantation, but the EGFR decreased slightly at the last 2 follow-ups (Figure 2).
dsdnawithHypocomplementemiaAnti-dsDNA levels were elevated in 5 patients at baseline and decreased significantly in the first week after transplantation, and this continued only until the first month after transplantation (Figure 2). The incidence of hypocomplementemia has increased from 66 at baseline7% down to 22 at the last follow-up2%。
Security:There were no anaphylaxis after MSCS transplantation, 1 patient developed transient hypertension after infusion, recovered after conventional treatment, no other acute or chronic adverse reactions were observed, and the overall survival rate at 12 months after transplantation was 100%.
Summary:Previous studies have shown that allogeneic AD-MSC transplantation has a good safety profile and is effective in reducing urine protein excretion and disease activity, but the transplant effect gradually wanes over time, which may be due to the fact that a single dose of AD-MSCs is not sufficient to maintain long-term remission in refractory LN, so multiple infusions may be required.
References:
1】wenyan cui , yunfei tian , guangliang huang , xinhui zhang, feigao li, xiuju liu. clinical research progress of novel biologics for the treatment of lupus nephritis. doi: 10.1007/s10238-023-01143-9.
2】amin ranjbar, halimeh hassanzadeh, faezeh jahandoust, raheleh miri,hamid reza bidkhori, seyed mostafa monz**i, nasser sanjar-mouss**i,maryam m. matin, zhaleh shariati-sarabi. allogeneic adipose-derived mesenchymal stromal cell transplantation for refractory lupus nephritis: results of a phase i clinical trial.