The subject matter relates to Semaphorin 3A (Sema3A) and its use in treatment and prognosis of Systemic Lupus Erythematosus (SLE). Provided are, inter-alia, methods of treating a subject afflicted with SLE, comprising administering to the subject a pharmaceutical composition comprising isolated Sema3A. Further provided are methods for prognosis of SLE, comprising measuring Sema3A serum concentration in a subject in need thereof.