Serum levels and significance of soluble B-cell maturation antigen in childhood-onset systemic lupus erythematosus with renal involvement

OBJECTIVE The aim of this study was to investigate serum levels of soluble B-cell maturation antigen (sBCMA) in childhood-onset systemic lupus erythematous (cSLE) patients with renal involvement, and to elucidate their association with clinical characteristics. METHODS 116 cases of cSLE patients with renal involvement (84 females and 32 males; median age 11.6 (10.1, 12.9) years) hospitalized in Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital, Sun Yat-sen University and 31 healthy controls (HCs) were enrolled. Serum concentrations of sBCMA were determined using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory information of cSLE patients were retrospectively analyzed. RESULTS Serum sBCMA levels were significantly increased in primary cSLE when compared with treated cSLE patients and HCs, whereas there was no significant difference between treated cSLE patients and HCs. Patients with high disease activity displayed higher serum sBCMA levels compared with those with no or mild to moderate disease activity. Positive correlation was observed between serum sBCMA levels and systemic lupus erythematosus disease activity index-2K (SLEDAI-2K), antinuclear antibody titers, anti-double-stranded DNA titers, erythrocyte sedimentation rate, and immunoglobulin G levels, while sBCMA levels were negatively correlated with blood white blood cell count, hemoglobin, platelet count, complement C3 and C4 levels. Serum sBCMA levels decreased as disease ameliorated after treatments among 11 cases with follow-up examinations. CONCLUSIONS In cSLE patients with renal involvement, serum sBCMA levels correlated significantly with disease activity, immunological, and hematological parameters, but not with renal parameters. Our results suggest the potential and significance of serum sBCMA as a biomarker in cSLE patients.

[1]  M. Talebi,et al.  B-cell maturation antigen targeting strategies in multiple myeloma treatment, advantages and disadvantages , 2022, Journal of translational medicine.

[2]  Jing Shi,et al.  Study on the Relationship Between the Expression of B Cell Mature Antigen and the Classification, Stage, and Prognostic Factors of Multiple Myeloma , 2021, Frontiers in Immunology.

[3]  Hyun-Dong Chang,et al.  Keeping up with the stress of antibody production: BAFF and APRIL maintain memory plasma cells. , 2021, Current opinion in immunology.

[4]  N. Xu,et al.  Baseline and Changes in Serum B-Cell Maturation Antigen Levels Rapidly Indicate Changes in Clinical Status Among Patients with Relapsed/Refractory Multiple Myeloma Starting New Therapy , 2021, Targeted Oncology.

[5]  T. Spektor,et al.  Baseline serum B‐cell maturation antigen levels predict time to disease progression for patients with smoldering multiple myeloma , 2021, European journal of haematology.

[6]  Yoshiya Tanaka,et al.  Systemic Lupus Erythematosus: Targeted Literature Review of the Epidemiology, Current Treatment, and Disease Burden in the Asia Pacific Region , 2020, Arthritis care & research.

[7]  W. Alturaiki The roles of B cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) in allergic asthma. , 2020, Immunology letters.

[8]  T. Spektor,et al.  Normalization of serum B‐cell maturation antigen levels predicts overall survival among multiple myeloma patients starting treatment , 2020, British journal of haematology.

[9]  E. Frangou,et al.  Update on the cellular and molecular aspects of lupus nephritis. , 2020, Clinical immunology.

[10]  T. Spektor,et al.  Estimating a normal reference range for serum B‐cell maturation antigen levels for multiple myeloma patients , 2020, British journal of haematology.

[11]  J. Muñóz-Valle,et al.  Analysis of the receptor BCMA as a biomarker in systemic lupus erythematosus patients , 2020, Scientific Reports.

[12]  H. Anders,et al.  Lupus nephritis , 2009, Nature Reviews Disease Primers.

[13]  C. Cunningham-Rundles,et al.  Serum B cell maturation antigen (BCMA) levels differentiate primary antibody deficiencies. , 2020, The journal of allergy and clinical immunology. In practice.

[14]  T. Chan,et al.  B Cell Abnormalities in Systemic Lupus Erythematosus and Lupus Nephritis—Role in Pathogenesis and Effect of Immunosuppressive Treatments , 2019, International journal of molecular sciences.

[15]  B. Wood,et al.  γ-secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma. , 2019, Blood.

[16]  N. Xu,et al.  Serum B-cell maturation antigen (BCMA) reduces binding of anti-BCMA antibody to multiple myeloma cells. , 2019, Leukemia research.

[17]  F. Mackay,et al.  Analysis of serum B cell‐activating factor from the tumor necrosis factor family (BAFF) and its soluble receptors in systemic lupus erythematosus , 2019, Clinical & translational immunology.

[18]  E. Meinl,et al.  Shedding of BAFF/APRIL Receptors Controls B Cells. , 2018, Trends in immunology.

[19]  H. Brunner,et al.  Childhood-Onset Systemic Lupus Erythematosus: A Review and Update. , 2018, The Journal of pediatrics.

[20]  Giovanna Flores-Mendoza,et al.  Mechanisms of Tissue Injury in Lupus Nephritis. , 2018, Trends in molecular medicine.

[21]  Saurabh Patil,et al.  The Role of B-Cell Maturation Antigen in the Biology and Management of, and as a Potential Therapeutic Target in, Multiple Myeloma , 2018, Targeted Oncology.

[22]  R. Hohlfeld,et al.  Human Plasmacytoid Dendritic Cells Display and Shed B Cell Maturation Antigen upon TLR Engagement , 2017, The Journal of Immunology.

[23]  T. Spektor,et al.  Serum B-cell maturation antigen: a novel biomarker to predict outcomes for multiple myeloma patients , 2016, Haematologica.

[24]  G. Valesini,et al.  Assessment of disease activity in Systemic Lupus Erythematosus: Lights and shadows. , 2015, Autoimmunity reviews.

[25]  T. Olsson,et al.  γ-secretase directly sheds the survival receptor BCMA from plasma cells , 2015, Nature Communications.

[26]  W. Stohl Therapeutic targeting of the BAFF/APRIL axis in systemic lupus erythematosus , 2014, Expert opinion on therapeutic targets.

[27]  J. Liese,et al.  Reference values for B cell subpopulations from infancy to adulthood , 2010, Clinical and experimental immunology.

[28]  Yen-Ming Hsu,et al.  Selectivity of BAFF/BLyS and APRIL for binding to the TNF family receptors BAFFR/BR3 and BCMA. , 2005, Biochemistry.

[29]  Lee Hebert,et al.  The classification of glomerulonephritis in systemic lupus erythematosus revisited. , 2004, Journal of the American Society of Nephrology : JASN.

[30]  R. Bram,et al.  BCMA Is Essential for the Survival of Long-lived Bone Marrow Plasma Cells , 2004, The Journal of experimental medicine.

[31]  M. Hochberg,et al.  Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. , 1997, Arthritis and rheumatism.

[32]  J. Klippel,et al.  Prognostic factors in lupus nephritis. Contribution of renal histologic data. , 1983, The American journal of medicine.