# IgA-containing immune complexes in plasmacytoid dendritic cell activation in SLE

> **NIH NIH R21** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2020 · $261,150

## Abstract

Project Summary
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the presence of
circulating autoantibodies to nucleic acids and to proteins with which they associate, termed anti-nuclear
antibodies (ANA). Immune complexes containing ANA and self-antigen from dying cells are pathological in SLE
due to immune complex deposition in organs, and they also promote a feed forward loop in SLE by enhancing
autoimmune responses in leukocytes that can endocytose these complexes. ANA immune complexes facilitate
nucleic acid entry to the endosome via receptors binding the Fc portion of antibodies, where the endosomal-
resident Toll-like receptors (TLRs) can promote cytokine production upon binding nucleic acids. Importantly,
most studies have focused on IgG isotype ANA immune complex uptake and function despite the fact that SLE
patients often have ANAs of multiple isotypes, including IgE and IgA. Plasmacytoid dendritic cells (pDCs) are
one leukocyte that internalizes ANA ICs implicated in SLE pathogenesis. pDCs use endosomal TLR7 and TLR9
to respond to nucleic acids, resulting in the secretion of type I IFNs. These cytokines have pleiotropic effects on
the immune response, all of which promote immune activation in SLE. pDCs express the IgG binding Fc receptor
FcγRII (CD32) through which they internalize IgG-containing ANA IC. Recently, pDC have been shown to
express FcεRI and internalize IgE-containing ANA IC leading to pDC IFNα production. However, IgE represents
only ~0.01% of total serum antibodies. In contrast, IgA makes up ~15% of serum antibodies and IgA ANA have
been identified in ~1/2 of SLE patients, yet the function of IgA in ANA IC has not been studied. Additionally, the
presence of the human-specific IgA Fc receptor FcαRI (CD89) has not been described on pDC. Here, we show
novel preliminary data that human pDC express the IgA FcR FcαRI (CD89), and that IgA in SLE serum is a
critical component of IC-mediated pDC IFNα secretion. We propose to 1) Determine the role of IgA
autoantibodies in anti-smRNP immune complex activation, and 2) Test the hypothesis that pDC from SLE
patients have increased responses to IgA-containing immune complexes. Experiments in this proposal will use
human samples from healthy control subjects and lupus patients available through the Benaroya Research
Institute Immune Mediated Disease Registry and Repository.

## Key facts

- **NIH application ID:** 10073210
- **Project number:** 1R21AI154841-01
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Jessica A Hamerman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $261,150
- **Award type:** 1
- **Project period:** 2020-05-22 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073210

## Citation

> US National Institutes of Health, RePORTER application 10073210, IgA-containing immune complexes in plasmacytoid dendritic cell activation in SLE (1R21AI154841-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10073210. Licensed CC0.

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