Systemic lupus erythematosus (SLE)

SLE is a chronic autoimmune disease in which the immune system attacks the body's own cells, forming immune complexes and damaging tissues. It predominantly affects women of reproductive age (9:1 ratio). Clinical presentation is extremely variable: from mild forms limited to skin and joint involvement to severe systemic variants with lupus nephritis, CNS involvement, and serositis. Standard therapy — glucocorticoids, hydroxychloroquine, methotrexate, azathioprine, mycophenolate mofetil, rituximab — controls disease in most patients but causes serious adverse effects with long-term use: osteoporosis, diabetes, obesity, and infectious complications. Mesenchymal cell therapy is considered a promising add-on for patients with refractory forms and for facilitating dose reduction of standard medications.

The global prevalence of SLE is estimated at 30–150 cases per 100,000 with a peak incidence between 15 and 45 years of age. The disease is significantly more common in women of African, Latin American, and Asian descent than in Europeans; these groups also more frequently develop lupus nephritis and severe organ involvement. The genetic contribution involves dozens of risk loci: HLA-DR2/DR3, polymorphisms of IRF5, STAT4, BLK, ITGAM, BANK1. Among environmental factors, ultraviolet exposure (a flare trigger), smoking, Epstein-Barr virus infection, and selected drugs (procainamide, hydralazine — drug-induced lupus-like syndrome) are well established. The hormonal axis explains female predominance: oestrogens sustain the autoimmune background, evidenced by exacerbations during pregnancy and on combined oral contraceptives in predisposed patients.

Pathogenetically, SLE is a loss of immune tolerance to self nucleic acids. Defective clearance of apoptotic cells exposes chromatin and RNA-protein complexes that activate Toll-like receptors TLR7 and TLR9 in plasmacytoid dendritic cells. The response is excessive production of type I interferons — the "interferon signature" in blood that has become a key biomarker. Subsequent activation of autoreactive B lymphocytes drives production of antinuclear antibodies: anti-dsDNA, anti-Sm, anti-Ro, anti-La, anti-RNP. Immune complexes deposit in kidneys (lupus nephritis), skin, synovium, and the vascular wall. Complement activation reduces C3 and C4 — a laboratory marker of flare. In parallel, the T-cell balance is perturbed: Th17 expansion against regulatory Treg depletion sustains chronic inflammation.

Diagnosis follows the EULAR/ACR 2019 criteria: entry requires antinuclear antibodies (ANA) ≥1:80, then weighted clinical and immunological domains. Key manifestations: cutaneous (malar rash, discoid lupus, photosensitivity), articular (non-erosive small-joint arthritis), renal (lupus nephritis classes I–VI per ISN/RPS), neuropsychiatric (NPSLE — 19 syndromes spanning migraine and cognitive dysfunction to psychosis), cardiovascular (pericarditis, Libman-Sacks endocarditis, accelerated atherosclerosis), pulmonary (pleuritis, pneumonitis, pulmonary hypertension), haematological (cytopenias). Disease activity is quantified using SLEDAI-2K; cumulative organ damage by the SLICC/ACR Damage Index. Remission is defined as SLEDAI=0 with prednisolone ≤5 mg/day (DORIS 2021); low disease activity (LLDAS) is a compromise on the path to remission.

Standard care in 2024 follows EULAR 2023 recommendations. Hydroxychloroquine is the foundation for all patients, reducing flares and thrombotic risk. For active disease, glucocorticoids are added (rapid control with kinetic dose reduction toward ≤5 mg/day), then methotrexate or azathioprine for moderate activity, mycophenolate mofetil or cyclophosphamide for severe systemic disease and lupus nephritis. Biologic therapy: belimumab (anti-BAFF) for active SLE with serological activity; anifrolumab (anti-IFNAR1, FDA-approved 2021) — the first specific inhibitor of the interferon pathway; rituximab (anti-CD20) for refractory haematological and neuropsychiatric manifestations; voclosporin for lupus nephritis. Despite this expanding armamentarium, 20–30% of patients have partially controlled disease and 30–50% accumulate adverse effects of long-term therapy — from osteoporosis and avascular necrosis of the femoral head to diabetes and infectious complications. These groups are the principal candidates for additional cell therapy.

Mesenchymal cell therapy targets SLE pathogenesis directly. After intravenous administration, UC-MSCs and placenta-derived MSCs restore the Treg/Th17 balance, suppress autoreactive B-cell proliferation through indoleamine 2,3-dioxygenase (IDO) and TGF-β, lower pro-inflammatory IL-6 and IL-17, protect endothelium from immune injury, and indirectly attenuate the type I interferon signature. The Chinese multicentre trial of Wang and colleagues (Arthritis Research & Therapy, 2014) in 40 patients with active refractory SLE — 95% with active lupus nephritis — demonstrated significant reduction in renal BILAG and 24-hour proteinuria after two intravenous UC-MSC infusions; 38 of 40 patients achieved a complete or partial clinical response. Six-year follow-up of this cohort revealed no late-onset malignancies or treatment-related deaths. The Hanshi United programme for SLE builds on these data: a standard course of three intravenous procedures of UC-MSC or placenta-derived MSCs at 15–20 day intervals; standard immunosuppression is maintained without dose reduction during the course; at 3–6 months the treating rheumatologist gradually tapers glucocorticoids and immunosuppressants based on SLEDAI and serology. In neuropsychiatric SLE a combined regimen with intrathecal administration is considered. In class IV lupus nephritis the optimal moment for cell therapy is after completion of induction with cyclophosphamide or MMF and achievement of partial response.