# Rheumatoid factor and cryoglobulinemia in chronic viral infection

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $290,250

## Abstract

Rheumatoid factor and cryoglobulinemia in chronic viral infection
Mixed cryoglobulinemia (MC) is strongly associated with chronic HCV infection. MC is an immune
complex-mediated medical condition and is found in 40-60% of chronic HCV patients, with 5-15%
patients develop clinical symptoms ranging from purpura, arthralgia, skin ulcers, peripheral
neuropathy, glomerulonephritis and myocarditis. HCV-related MC greatly affects patients’ quality
of life therefore a priority for HCV treatment. The pathogenic mechanism of MC is poorly
understood, although it is suggested that HCV infection can stimulate unregulated B cell
proliferation, and in some cases, the production of anti-antibody, i.e. rheumatoid factor (RF), of
the IgM isotype. The HCV-induced RF in turn forms immune complexes with anti-HCV antibodies
and HCV antigens that are sensitive to precipitation at temperature below 37oC which are known
as cryoglobulins. However, recent studies reported that successful HCV treatment can improve
symptoms of MC but cryoglobulins may still persist, indicating other non-viral antigens may be
involved in the formation of cryoglobulins. In Aim 1 of this proposed study, we will identify the
antigens present in cryoglobulins by a proteomic approach, both before and after successful HCV
treatment, in order to decipher the composition and diversity of cryoglobulins and the mechanism
of their formation. In Aim 2, we will study RF from MC patients in order to understand the diversity
of antibody gene usage and their target epitopes, and whether HCV clearance may restore RF to
normal level. Our goal is to develop novel experimental systems and reagents in this
exploratory/developmental project that will be useful for understanding the disease mechanism of
MC, and for defining the molecular properties of RF in different microbial infections and
autoimmune conditions in the long term.

## Key facts

- **NIH application ID:** 9896553
- **Project number:** 1R21AI144232-01A1
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Mansun Law
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $290,250
- **Award type:** 1
- **Project period:** 2019-12-18 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896553

## Citation

> US National Institutes of Health, RePORTER application 9896553, Rheumatoid factor and cryoglobulinemia in chronic viral infection (1R21AI144232-01A1). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9896553. Licensed CC0.

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