Anemia in Systemic Lupus Erythematosus Associates the Disease Activity, and Serum Levels of Semaphorin-3A and ds-DNA Autoantibodies not Anti-Erythropoietin Autoantibodies

Introduction: Immune dysregulation systemic in lupus erythematosus (SLE), a heterogeneous autoimmune disease, encompasses the innate and adaptive immunity. The accumulation of immune complex induces the progressive organ damage in the kidney, brain, skin, hematopoietic system, joints, eye, endocrine glands, and other organs, with great morbidity. Aim: to substantiate the proposed role of anti-erythropoietin (EPO) autoantibodies in systemic lupus erythematous (SLE)-induced anemia. Subjects and Methods: This is a cross-sectional study sequentially enrolled disease duration- and socio-demographically-matching 50 SLE patients; 25 each of active and inactive disease, compared to 25 socio-demographically-matching healthy controls. Clinical evaluation, serum anti-EPO, anti-double‐stranded DNA (dsDNA), and antinuclear antibodies (ANA) autoantibodies, C-reactive protein (CRP), semaphorin-3A (SEMA-3A) and complement factors C3 and C4 were ELISA immunoassayed. Hemoglobin (Hb) level, white blood cell count (WBCs) and erythrocyte sedimentation rate (ESR) were estimated. Results: Levels of ANA (79% vs. 56%) and ds-DNA (76% vs. 84%) were non-significantly different among the two patients’ groups. Anti-EPO was more prevalent among patients with active disease (20% vs. 8%; P = 0.05). The major systemic impact of active SLE afflicted hematological system (98 vs. 68%; P = 0.023), and anemia was significantly more prevailing among active than inactive SLE patients (P < 0.001), although Hb did not correlate with anti-EPO. SLE disease activity index (SLEDAI), disease severity distribution, CRP, and ESR were higher, while levels of complements C3 and C4 and SEMA-3A were significantly lower in active than inactive SLE patients (P < 0.001). The multivariate logistic regression analyses postulated that SLEDAI, ds-DNA and SEMA3A were nonsignificant predictors for anemia. Bivariate analysis of SLE biomarker potential of each of SEMA3A and anti-EPO revealed significant association (P < 0.001 and = 0.05, respectively). Conclusion: Higher serum anti-EPO antibodies may partially explain the presumed resistance against EPO action and SLE-induced anemia, in a milieu of immune hyperactivation