Systemic lupus erythematosus in a 15-year-old female with multiple splenic nodules: A case report.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease primarily affecting young females. SLE can invade any organ, and various forms of splenic invasion have been reported. Manifestations include splenomegaly and splenic infarction, rupture, and calcification. The study encountered a rare case of splenic involvement, with nodules of various sizes without calcifications or ruptures. CASE SUMMARY: A 15-year-old girl presented with arthralgia, weight loss, fever, increased levels of inflammatory markers, and positive antinuclear antibody test results. The patient was diagnosed with SLE. She was asymptomatic while taking steroids and hydroxychloroquine. Ten months after discharge, the patient developed a fever and abdominal pain. Lupus enteritis was suspected, and abdominopelvic computed tomography (AP-CT) was performed. There were no specific findings in the gastrointestinal tract, but multiple splenic nodules were observed. Infection or hemangioma was considered; however, no specific radiological findings were observed. A biopsy of the spleen was performed to determine the possibility of malignancy. The histological findings of the spleen included extensive periarteriolar necrosis with hematoxylin bodies and numerous karyorrhectic debris. Based on the biopsy results, the patient was diagnosed with an SLE flare-up and was maintained on high-dose steroids and immunosuppressants. CONCLUSION: As disease activity increased, multiple nodules in the spleen that were previously unseen were observed using AP-CT and histologically confirmed. Spleen invasion by SLE can appear in multiple nodular forms and patterns. Therefore, physicians should consider these findings when differentiating these nodules from infections and malignancies.

Cystatin C as a Predictor of Renal Function and Methotrexate-Associated Toxicities in Patients With Rheumatoid Arthritis.

OBJECTIVE: Methotrexate (MTX) is an anchor drug for most patients with rheumatoid arthritis (RA); however, its use may be limited depending on renal function. Therefore, this study aimed to examine the discrepancy in the estimated glomerular filtration rate (eGFR) using conventional serum creatinine (SCr)-, cystatin C-, and MTX-associated toxicities in patients with RA. METHODS: In total, 436 patients were enrolled, and eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on both cystatin C and SCr levels. The CKD and MTX dosing stages were classified according to eGFR. MTX-associated toxicities were also evaluated. RESULTS: The mean eGFR using CKD-EPI cystatin C (CKD-EPIcys) was 89.44 mL/min/1.73 m2, lower than the eGFR using CKD-EPI SCr (CKD-EPISCr) of 95.55 mL/min/1.73 m2. After converting eGFR to CKD-EPIcys by CKD-EPISCr, 29.8% of patients were reclassified to a higher stage according to the Kidney Disease: Improving Global Outcomes CKD stage. Also, according to the MTX guidelines, 6.4% of the group with an eGFR > 50 mL/min/1.73 m2 were reclassified to eGFR 10-50 mL/1.73 m2, requiring dose adjustment. The incidence of MTX-associated toxicities, such as anemia, leukopenia, and nephrotoxicity, was significantly higher in the CKD stage-changed group than in the nonstage-changed group. CONCLUSION: Our results showed that eGFR based on SCr was overestimated compared with eGFR based on cystatin C. In addition, we demonstrated that MTX-associated toxicities were significantly increased in the group with a changed stage when the eGFR was converted from CKD-EPISCr to CKD-EPIcys.

The Expression of Immunomodulation-Related Cytokines and Genes of Adipose- and Bone Marrow-Derived Human Mesenchymal Stromal Cells from Early to Late Passages.

BACKGROUND: Mesenchymal stromal cells (MSCs) are multipotent stem cells that can differentiate into several cell types. In addition, many studies have shown that MSCs modulate the immune response. However, little information is currently available regarding the maintenance of immunomodulatory characteristics of MSCs through passages. Therefore, we investigated and compared cytokine and gene expression levels from adipose (AD) and bone marrow (BM)-derived MSCs relevant to immune modulation from early to late passages. METHODS: MSC immunophenotype, growth characteristics, cytokine expressions, and gene expressions were analyzed. RESULTS: AD-MSCs and BM-MSCs had similar cell morphologies and surface marker expressions from passage 4 to passage 10. Cytokines secreted by AD-MSCs and BM-MSCs were similar from early to late passages. AD-MSCs and BM-MSCs showed similar immunomodulatory properties in terms of cytokine secretion levels. However, the gene expressions of tumor necrosis factor-stimulated gene (TSG)-6 and human leukocyte antigen (HLA)-G were decreased and gene expressions of galectin-1 and -3 were increased in both AD- and BM-MSCs with repeated passages. CONCLUSION: Our study showed that the immunophenotype and expression of immunomodulation-related cytokines of AD-MSCs and BM-MSCs immunomodulation through the passages were not significantly different, even though the gene expressions of both MSCs were different.

Treatment of Collagen-Induced Arthritis Using Immune Modulatory Properties of Human Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have immune modulatory properties. We investigated the potential therapeutic effects of human bone marrow (BM)-, adipose tissue (AD)-, and cord blood (CB)-derived MSCs in an experimental animal model of rheumatoid arthritis (RA) and explored the mechanism underlying immune modulation by MSCs. We evaluated the therapeutic effect of clinically available human BM-, AD-, and CB-derived MSCs in DBA/1 mice with collagen-induced arthritis (CIA). CIA mice were injected intraperitoneally with three types of MSCs. Treatment control animals were injected with 35 mg/kg methotrexate (MTX) twice weekly. Clinical activity in CIA mice, degree of inflammation, cytokine expression in the joint, serum cytokine levels, and regulatory T cells (Tregs) were evaluated. Mice treated with human BM-, AD-, and CB-MSCs showed significant improvement in clinical joint score, comparable to MTX-treated mice. Histologic examination showed greatly reduced joint inflammation and damage in MSC-treated mice compared with untreated mice. Microcomputed tomography also showed little joint damage in the MSC-treated group. MSCs significantly decreased serum interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, and interferon-γ and increased IL-10 and transforming growth factor-ß levels. Tregs were increased in mice treated with MSCs compared to untreated or MTX-treated mice. Human BM-, AD-, and CB-MSCs significantly suppressed joint inflammation in CIA mice. The cells decreased proinflammatory cytokines and upregulated anti-inflammatory cytokines and induced Tregs. Therefore, our study suggests that the use of human BM-, AD-, and CB-MSCs could be an effective therapeutic approach for RA.

Two cases of refractory thrombocytopenia in systemic lupus erythematosus that responded to intravenous low-dose cyclophosphamide.

Treatment of thrombocytopenia in systemic lupus erythematosus (SLE) is considered in cases of current bleeding, severe bruising, or a platelet count below 50,000/µL. Corticosteroid is the first choice of medication for inducing remission, and immunosuppressive agents can be added when thrombocytopenia is refractory to corticosteroid or recurs despite it. We presented two SLE patients with thrombocytopenia who successfully induced remission after intravenous administration of low-dose cyclophosphamide (CYC) (500 mg fixed dose, biweekly for 3 months), followed by azathioprine (AZA) or mycophenolate mofetil (MMF). Both patients developed severe thrombocytopenia in SLE that did not respond to pulsed methylprednisolone therapy, and started the intravenous low-dose CYC therapy. In case 1, the platelet count increased to 50,000/µL after the first CYC infusion, and remission was maintained with low dose prednisolone and AZA. The case 2 achieved remission after three cycles of CYC, and the remission continued with low dose prednisolone and MMF.