Cancer Institute A national cancer institute
designated cancer center

Scott Boyd, MD PhD

Publication Details

  • An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1. The Journal of clinical investigation Bonsignori, M., Wiehe, K., Grimm, S. K., Lynch, R., Yang, G., Kozink, D. M., Perrin, F., Cooper, A. J., Hwang, K. K., Chen, X., Liu, M., McKee, K., Parks, R. J., Eudailey, J., Wang, M., Clowse, M., Criscione-Schreiber, L. G., Moody, M. A., Ackerman, M. E., Boyd, S. D., Gao, F., Kelsoe, G., Verkoczy, L., Tomaras, G. D., Liao, H. X., Kepler, T. B., Montefiori, D. C., Mascola, J. R., Haynes, B. F. 2014

    Abstract:

    Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1-infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1-infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient's plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells.

    View details for DOI 10.1172/JCI73441

    View details for PubMedID 24614107

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