March 17, 2014
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Autoreactive antibody neutralized HIV-1 infection in patient with lupus

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In an HIV patient with systemic lupus erythematosus and chronic HIV-1 infection, the development of a broadly HIV-1 neutralizing antibody was associated with a controlled viral load and plasma HIV-1 neutralization, according to recent findings published in The Journal of Clinical Investigation.

“Over the years, we have searched for and now have found one person with systemic lupus erythematosus who was also chronically infected with HIV to determine if this person could make broad neutralizing antibodies,” Barton F. Haynes, MD, director of the Duke Human Vaccine Institute, said in a press release. “We found that the patient did indeed make these important antibodies, and by determining how this immune response occurred, we have enhanced our understanding of the process involved.”

A 33-year-old patient was evaluated 14 years after HIV transmission and 6 years after systemic lupus erythematosus onset. The patient demonstrated controlled viral load (<5,000 copies/mL) while off antiretroviral therapy and in the absence of human leukocyte antigen phenotypes. After collecting and culturing memory B cells from the patient, the researchers identified a broadly HIV-1 neutralizing antibody (BnAb), CH98. CH98 acts on the CD4 binding site of HIV-1 envelope glycoprotein 120. CH98 reacted with double-stranded DNA (dsDNA), an antigen specifically related to lupus and bound to dsDNA. The patient’s blood also showed anti-dsDNA activity. CH98 demonstrated a mutation frequency of 25% in the heavy-chain variable domain and 15% in the light-chain variable domain. CH98 also had a long heavy-chain complementarity-determining region 3 (HCDR3) and a deletion in the light-chain complementarity-determining region 1 (CDR1).

According to the researchers, the anti-dsDNA reactivity by an HIV-1 CD4 binding site BnAb in this patient suggests that the poor immune tolerance mechanisms associated with autoimmune disease may promote the production of BnAbs.

Disclosure: The researchers report no relevant financial disclosures.