# Injection Drug Use Alters Plasma Regulation of the B Cell Response

## TL;DR

This study shows that injection drug use changes proteins in the blood, which affects how B cells respond, potentially increasing infection risk.

## Contribution

The study reveals how injection drug use alters the plasma proteome and its regulation of B cell responses.

## Key findings

- The plasma proteome of people who inject drugs (PWID) shows significant changes in immune-related proteins.
- PWID plasma suppresses B cell proliferation and alters their transcriptional profiles toward germinal center B cell-like states.
- Altered plasma proteins in PWID include complement components, immunoglobulins, and inflammatory mediators.

## Abstract

The opioid epidemic continues to be a major public health issue that includes millions of people who inject drugs (PWID). PWID have increased incidence of serious infections, including HIV as well as metabolic and inflammatory sequelae. We sought to discern the extent of systemic alterations in humoral immunity associated with injection drug use, including alterations in the plasma proteome and its regulation of B cell responsiveness. Comprehensive plasma proteomics analysis of HIV negative/hepatitis C negative individuals with a history of recent injection heroin use was performed using mass spectrometry and ELISA. The effects of plasma from PWID and healthy controls on the in vitro proliferation and transcriptional profile of B cell responses to stimulation were determined by flow cytometry and RNA-Seq. The plasma proteome of PWID was distinct from healthy control individuals, with numerous immune-related analytes significantly altered in PWID, including complement (C3, C5, C9), immunoglobulin (IgD, IgM, kappa light chain), and other inflammatory mediators (CXCL4, LPS binding protein, C-reactive protein). The plasma of PWID suppressed the in vitro proliferation of B cells. Transcriptome analysis indicated that PWID plasma treatment increased B cell receptor and CD40 signaling and shifted B cell differentiation from plasma cell-like toward germinal center B cell-like transcriptional profiles. These results indicate that the systemic inflammatory milieu is substantially altered in PWID and may impact their B cell responses.