A person’s ability to manufacture pathogenic immunoglobulin in SLE and sustain its production depends on intrinsic abnormalities of B and T lymphocytes, and those in turn depend on inheriting an appropriate number of susceptibility genes, lacking protective genes, and encountering an environmental stimulus that sets the whole process into action. The aim of this work is to elucidate the role of HLA genes and autoantibodies in the clinical presentation of SLE and thus to evaluate the usefulness of such genetic and autoimmune markers in predicting disease course and outcome. Fifty three Egyptian patients with childhood onset systemic lupus erythematosus were examined for clinical manifestations, detection of ANA, anti-DNA, anti-Ro (SS-A), anti-La (SS-B), anti-Sm, anti-RNP and anti-cardiolipin antibodies and for determination of HLA-DR alleles. This study showed an association of certain MHC antigens and autoantibodies with the development of certain disease manifestations.