Soluble Plasma Proteins of Tumor Necrosis Factor and Immunoglobulin Superfamilies Reveal New Insights into Immune Regulation in People with HIV and Opioid Use Disorde

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Abstract Opioid Use Disorder (OUD) is present in high frequency in people with HIV (PWH). This study investigated proteins of the TNF and Immunoglobulin superfamilies (SF) in relation to Flu vaccine responses in PWH with and without OUD. 210 participants (median age 46 years) were recruited into OUD groups: HIV+OP+ and HIV-OP+, and non-opioid users: HIV+OP- and HIV-OP-. Flu vaccine titers post-vaccination at 21-28 days (T2) and fold change (T2/T0) were higher in people with OUD compared to PWH without Opioid use, while being equivalent to controls (HIV-OP-). 48 soluble molecules of the Tumor necrosing factor (TNF) and Immunoglobulin (Ig) superfamilies (SF) were analyzed in plasma by multiplex Luminex technology. Both OP+ groups (HIV+OP+ and HIV- OP+) had higher co-stimulatory TNF SF molecules including 4-1BB, OX-40, CD40 that were positively correlated with Flu vaccine responses. The HIV+ OP- group displayed a different profile, with high Ig SF molecules including PD-L2, CTLA-4 and Perforin, of which PD-L2 was negatively associated with Flu vaccine titers. The higher Flu vaccine response in the groups with OUD (HIV+OP+ and HIV- OP+) could be attributed to high levels of specific plasma proteins of the TNF superfamily that are known to be important for T cell activation, proliferation, and T-B interactions needed for antibody responses and could have negated the immunosuppressive effects of HIV. These findings could lead to development of new diagnostic and therapeutic tools.

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