What: 
The 2018 American College of Rheumatology/American Rheumatology Health Professionals Annual Meeting.

When: 
Oct. 19–24, 2018

Predicting Who Might Develop Arthritis from Cancer Immunotherapy

When: Sunday, Oct. 21, 9 a.m. CT

Where: McCormick Place, Poster Hall F2

Session: Miscellaneous Rheumatic and Inflammatory Diseases Poster I: Checkpoint Inhibitors, Retroperitoneal Fibrosis

Johns Hopkins researchers found that people with arthritis caused by treatment with a specific type of cancer immunotherapy were more likely than healthy controls to have versions of a gene that is associated with rheumatoid arthritis. The findings suggest that people who develop inflammatory arthritis due to cancer immunotherapy may be genetically predisposed to autoimmune reactions such as rheumatoid arthritis, and that we may be able to eventually identify those at risk and personalize their cancer treatment to avoid these long-term consequences.

A small percentage of people on cancer immunotherapy—a new method of treating cancer that uses the body’s own immune system—specifically people using immune checkpoint inhibitors, can develop inflammatory arthritis, which can cause pain, swelling and stiffness in the joints. But, physicians don’t know what genetic risk factors make someone susceptible to developing the condition.

The researchers analyzed a set of genes that makes proteins that help the immune system identify “self” versus foreign cells. They sequenced these genes and compared those from 26 people with cancer immunotherapy-induced arthritis to 726 healthy controls and 220 people with rheumatoid arthritis, a condition in which the immune system attacks the joints. They found that 61 percent of the participants with cancer immunotherapy-induced arthritis had a common variation of the DRB1 gene more often found in people with rheumatoid arthritis.

Separately, the researchers analyzed the antibodies found in the blood of people with cancer immunotherapy-induced arthritis. They found that people with cancer immunotherapy-induced arthritis were less likely to have rheumatoid factor and anti-cyclic citrullinated peptide—both autoimmune antibodies found in people with rheumatoid arthritis. This intrigued the researchers since those autoantibodies in rheumatoid arthritis are associated with the gene versions highlighted in the study.

Laura Cappelli, M.D., M.H.S., M.S., assistant professor of medicine at the Johns Hopkins University School of Medicine, and her team hope they can find ways to identify people at risk for developing inflammatory arthritis from cancer immunotherapy so they can use a personalized approach to better warn of potential side effects and prepare for the risks, or alternatively try a different cancer therapy less likely to cause an autoimmune reaction. Both inflammatory arthritis due to cancer immunotherapy and rheumatoid arthritis can be treated with anti-inflammatories, steroids and immune suppressants, but there is no cure.

African-American Gene Differences May Explain Worse Lupus-Caused Kidney Disease and Reduced Response to Treatment

Where: McCormick Place, W183a

When: Monday, Oct. 22, 5:30 p.m. CT

Session: 4M108 ACR Abstract: SLE–Etiology & Pathogenesis I (1893–1898)

In the U.S., 1.5 million people have some form of lupus, and more than 40 percent of African-Americans with lupus develop kidney disease due to lupus. Now, researchers at Johns Hopkins have uncovered new data that can help improve the delivery of precision medicine. As part of the National Institutes of Health Accelerating Medicines Partnership, Johns Hopkins Medicine researchers may have found genetic differences between African-American and white people that control immune reactions and could cause variations in how the disease manifests and responds to treatment.

The study presented by Andrea Fava, M.D., a research and clinical fellow at Johns Hopkins Medicine, looked at kidney biopsies from 13 African-American and seven white people with lupus-induced kidney disease. The researchers sequenced the RNA of each cell in the biopsy to see what genes were turned on and identified 16 different immune cell types.

They found that biopsies from African-Americans had many genes turned on related to immune responses against viruses, known as the interferon response, in many of their CD4+ lymphocytes (a type of white cell) that weren’t seen at such high levels in the white patients. This genetic signature may indicate that African-Americans with lupus-induced kidney disease have stronger interferon response within their immune system, which may make them more prone to lupus complications and resistant to treatment.

In biopsies of white patients more than in those of African-Americans, they detected genes turned on at high levels that may help dendritic cells, another type of immune cell, to calm down excess inflammation, which may explain more kidney damage in African-Americans with lupus. The researchers found several other genetic programs that were differentially regulated in the two groups. They say that, while these results are preliminary, they could help to explain why lupus kidney disease is worse in African-Americans.

Fava, working with Michelle Petri, M.D., M.P.H., says their results suggest that ethnicity can predict the type of autoimmune response in the kidneys of patients with lupus, and that this information can be used to develop better targeted treatments for those with certain genetic profiles who don’t respond as well to current therapies.

Personalizing Lupus Medication Doses to Minimize Damage to the Eye’s Retina

Where: McCormick Place, W185a

When: Tuesday, Oct. 23, 5:45–6 p.m. CT

Session: 5T111 ACR Abstract: SLE–Clinical IV: Clinical Outcomes (2892–2897)

Johns Hopkins researchers found that using a blood test to detect concentrations of the lupus drug hydroxychloroquine could help predict whether a person was at risk of developing damage to the eye’s retina—known as retinopathy—due to the drug and could inform treatment decisions and follow-up care. Using this blood test could lead to a more personalized dose of the lupus medication and a patient monitoring strategy to prevent harmful side effects.

The drug hydroxychloroquine, originally a malaria drug, is used to control autoimmune diseases such as lupus, which causes rash, arthritis and kidney disease that can lead to kidney failure. Using hydroxychloroquine for more than 16 years can increase the risk of developing retinopathy, which might lead to loss of vision if the drug were continued.

Michelle Petri, M.D., M.P.H., director of the Johns Hopkins Lupus Center and professor of medicine at the Johns Hopkins University School of Medicine, looked at data from 477 people with lupus, measured hydroxychloroquine in their blood and reviewed their monitoring tests for retinopathy. They found the longer one took the drug, the more at risk they were for developing retinopathy. They also found people who were white, male or older were the most at risk. The highest levels of hydroxychloroquine in the blood predicted a higher risk of retinopathy. Petri says that rheumatologists could increase monitoring for retinopathy in those patients with high levels of hydroxychloroquine in their blood, or could decrease the dose if lupus was under control.
 

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