Feinstein ‘risk index’ could get the jump on lupus

Antibody of evidence: By studying blood samples from five different cohorts, Feinstein Institute researchers have developed a system for predicting lupus risk factors.

A complex research effort led by top Feinstein Institute scientists has opened the door to a wide range of early-intervention protocols for the dreaded disease lupus.

A Feinstein Institute for Medical Research team led by immunologist and Professor Betty Diamond has developed a system for identifying a person’s risk for lupus by examining antibodies and a specific protein complex found in the blood.

Ideally, scientists may use these unique markers to anticipate impending lupus flare-ups or prescribe preventative measures in at-risk groups.

Diamond, head of the Feinstein Institute’s Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases and one of the Northwell Health system’s top autism researchers, is the corresponding author – and one of 18 authors total – of a paper discussing the lupus-focused research, published this month by the open-access journal Molecular Medicine.

The potential breakthroughs stem from simple curiosity – in this case, researchers wondered why women of West African descent were more susceptible to lupus, a systemic autoimmune disease in which the body’s immune system mistakenly attacks the body’s healthy tissue.

West African descendants have “a 3- to 4-fold greater incidence of [systematic lupus erythematosus] than Caucasians,” according to the paper, and Diamond et al wanted to know why.

Betty Diamond: Sees lupus coming.

“A better understanding about the risk of lupus and why it differs between populations could help us better treat or even prevent people from getting the condition,” noted Diamond, who’s also a professor at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell and head of its PhD program.

Based on examinations of blood serum from five different groups of women – some infected, some healthy – the research team ultimately developed an index it says accurately identifies lupus risk levels in all demographics.

Their study groups: 40 West African women with a history of malaria infection, 51 African American lupus patients, 80 healthy African American women and 98 healthy sisters of lupus patients, all compared to a control group of 16 health Caucasian women.

The predictions are based on the relative levels of certain immunoglobin antibodies, plus the levels of “complement component 1q,” a protein complex that activates when the body’s “complement system” – an immune system reinforcer that enhances antibodies’ ability to clear out damaged cells – gears up, as it does when lupus comes calling.

According to the researchers’ findings, risk indexes were predictably highest in existing SLE patients – but second-highest in the unaffected sisters of lupus patients and third-highest in healthy African American women.

The lowest risks were shared by malaria-exposed West African women and the healthy Caucasian group.

The findings confirmed the researchers’ hypothesis, that high levels of Immunoglobin G, low levels of Immunoglobin M and low levels of C1q “predispose to lupus.” They also show that exposure to malaria – a mosquito-borne infectious disease with its own set of headaches – increases both Immunoglobin M and C1q levels, which “may delay onset of lupus in genetically predisposed individuals,” according to the Feinstein Institute.

Years of laboratory work will follow, but the risk index developed by Diamond and her co-authors – including Peter Gregersen, head of the Feinstein Institute’s Robert S. Boas Center for Genomics & Human Genetics and a frequent Diamond collaborator – may ultimately pave the way for smarter and more efficient early-intervention protocols and a wider range of treatments, according to Feinstein Institute President and CEO Kevin Tracey.

“Dr. Diamond is a recognized leader in lupus research,” Tracey said in a statement. “Now her discovery of blood markers to assess disease risk also gives new insights into early diagnosis and hope for potential therapeutic pathways.”

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