SUN-024 SERUM FREE LIGHT CHAIN AS SURROGATE MARKER FOR RENAL ACTIVITY IN LUPUS NEPHRITIS

Abstract

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can potentially cause inflammation and damage to any organ system. Lupus Nephritis (LN) is a major risk factor for morbidity and mortality in SLE and 10% of patients with LN will develop end-stage renal disease (ESRD). The etiology is believed to be multi-factorial with both environmental and genetic factor contributing to the development of SLE. B cell activation is central in the disease mechanism of SLE and characterized by the production of autoantibodies and during active disease, extensive polyclonal B cell hyperactivity is observed. Excess immunoglobulin (Ig) light chains are produced in proportion to Ig heavy chains during antibody synthesis in plasma cells thus free light chains (FLC) are released to circulation. In this study, we evaluated the utility of polyclonal serum FLC measurements as a clinical biomarker of LN disease activity. This is a cross sectional, prospective, convenient sampling study recruiting patients with LN attending glomerulonephritis clinic at University Malaya Medical Center (UMMC). The patients were divided into active LN, remission and healthy group. UMMC healthcare staffs were recruited for healthy cohort. Active diseases defined as pathological diagnosis on renal biopsy, increased from baseline serum creatinine or proteinuria (with concurrent increase in immunosuppression). Investigations include serum creatinine, urine protein creatinine ratio (PCR), serum complements (C3, C4), double-stranded DNA (dsDNA) antibody and serum FLC (kappa and lambda). SLEDAI 2K score was assessed at the same setting. A total of 65 subjects were analyzed in this study. Median age for our patient was 34, IQR (16.5) years old. Twenty patients were in active group, 23 patients were in remission and the rest consist of healthy group. Median SLEDAI 2K score was 8, IQR (4) and 4, IQR (6) in active and remission group respectively. The serum FLC kappa and lambda were raised in active group with the median of 34.2, IQR (43.7) mg/L, and 40.3, IQR (31.0) mg/L. In the remission group, their FLC kappa and lambda were 26.2, IQR (17.0) mg/L, and 32.7, IQR (18.5) mg/L respectively. Although numerically higher in active LN group, it was not statistically different as compare to remission group. Other clinical biomarkers, namely C3, C4, anti-dsDNA and ANA were abnormal in majority LN patients and did not differ between active and remission status. The Spearman’s correlation test showed that serum FLC kappa and lambda correlated well with SLEDAI 2K score with r = 0.586 (p < 0.001) and r = 0.689 (p < 0.001). Serum FLC (kappa and lambda) level were numerically higher in active LN as compare to remission group. Perhaps this could be a good supplementary tool to ascertain information regarding disease activity in LN patients. A more robust clinical trial is necessary if serum FLC were to be used as surrogate marker to avoid invasive renal biopsy procedure in determining active disease in LN.