VH4-34 encoded antibody in systemic lupus erythematosus: effect of isotype

OBJECTIVE: To determine the clinical significance of elevated serum levels of VH4-34 encoded IgM and IgG antibodies with respect to the clinical characteristics of systemic lupus erythematosus (SLE). METHODS: VH4-34 encoded IgM and IgG immunoglobulin was measured in 95 patients with SLE by ELISA using antiidiotype monoclonal antibody (Mab) 9G4. SLE disease activity, severity, and damage were assessed by visual analog scales, Systemic Lupus Activity Measure, Lupus Severity of Disease Index, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Presence of VH4-34 encoded antibodies on patients' B lymphocytes was analyzed by flow cytometry using Mab 9G4. RESULTS: Fifty-two of 95 patients with SLE had elevated levels of VH4-34 encoded antibodies of IgG isotype; 17 patients with VH4-34 IgG had elevated VH4-34 of the IgM isotype. Forty-three of the 95 patients had normal levels of VH4-34 encoded antibodies. When disease severity was correlated to VH4-34 isotype, patients with circulating VH4-34 IgG but without IgM had significantly more severe disease compared to patients who had VH4-34 of both isotypes. Eighty-six percent of patients with SLE nephritis and 100% of those with central nervous system (CNS) lupus had VH4-34 IgG without IgM. In vivo, VH4-34 encoded antibodies were found to bind autologous B lymphocytes. CONCLUSION: Presence of VH4-34 IgG in the absence of VH4-34 IgM was the finding most strongly associated with severe SLE, nephritis, and CNS lupus, suggesting that isotype switching of VH4-34 encoded antibodies or loss of VH4-34 IgM encoded antibodies may influence the progression of disease in SLE.