Sep. 18, 2012

Biomarker-Driven Assessment of Lupus Progression

Autoantibody profiling to follow evolution of lupus syndromes
Olsen NJ, Li QZ, Quan J, Wang L, Mutwally A, and Karp DR. (2012). Arthritis Research & Therapy 14: R174. [Epub ahead of print]

What is the topic?

Lupus can go unrecognized or undiagnosed even while a person has already entered the early stages of the disease. This is because the initial symptoms of lupus are variable and involve relatively common complaints typical of causes other than lupus. Early diagnosis of lupus would be greatly facilitated by the identification of biomarkers in the blood that are typical of the early stages of lupus.

What did the researchers hope to learn?

The researchers hoped to learn about the clinical evolution of lupus-related autoimmunity and whether it could be related to levels of specific autoantibodies, especially during the early stages of lupus.

Who was studied?

The study included 22 people with “incomplete lupus” (see below) who were recruited to the study from the University of Texas Southwestern Medical Center clinics at Parkland Hospital and the Aston Ambulatory Care Center in Dallas, Texas.

How was the study conducted?

Patient examination, interview, and medical record review for people with “incomplete lupus” (i.e., showed less than four diagnostic criteria for lupus upon study entry) were used to determine the presence of criteria for systemic lupus erythematosus. The 22 patients all had at least two blood samples drawn within the past five years. This blood was analyzed for early biomarkers of lupus with appropriate laboratory techniques. These early biomarkers included more than 80 autoantigens that were used to profile immunoglobulin G (IgG) and immunoglobulin M (IgM) types of autoantibodies. Levels of these autoantigens were correlated with clinical progression of lupus. In addition, scoring systems were developed (based on demographic information and autoantibody profiles) to identify and compare risk of lupus progression between people whose lupus was progressing over time (“progressors”) and those in whom lupus was not progressing over time (“non-progressors”).

What did the researchers find?

Most of the patients included in the study were either African-American or Hispanic/Latino women. They were, on average, 48 years old, had at least two diagnostic criteria for lupus upon study entry, and most were positive for anti-nuclear antibodies. None of the patients included in the study were taking high doses of steroids or cyclophosphamide during the study period.

Three of the 22 patients (14%) included in the study acquired additional lupus (diagnostic) criteria over an average follow-up period of 3.8 years since the first study visit. These three patients were designated as “progressors” to indicate their progression towards a full-blown diagnosis of lupus. The progressors were all females, aged 27-33 years old at study entry. As compared to the non-progressors (average age = 51 years), the progressors (average age = 30 years) were, on average, significantly younger in age.

IgG, but not IgM, autoreactivity was significantly increased (from study visit 1 to study visit 2) in all three progressor vs. non-progressor patients. Fifteen individual IgG autoantibodies were significantly elevated in the progressor vs. non-progressor patients. None of the non-progressor patients had elevated levels of IgG autoantibodies. In addition, two of the three progressors showed increases in levels of specific autoantibodies (namely, SS-A-related antigens and either Ro/SS-A or Ro/SS-B) between the two study visits, and all three progressors showed increases in La/SS-B. None of the non-progressor patients showed an increase in La/SS-B.

Scoring systems indicating risk of lupus progression showed significantly increased risk in the progressors vs. non-progressors.

What were the limitations of the study?

This study should be interpreted with caution due to the small number of lupus patients who were studied, only three of which progressed to lupus. In addition, the data were obtained retrospectively (i.e., by review of their medical records after the fact). Finally, there was a relatively short period of time between the two study visits, which may have prevented the observation of more patients progressing to lupus.

What do the results mean for you?

The results suggest that the following are significant risk factors for lupus progression: female gender, age less than 40 years, high baseline positivity for anti-nuclear antibodies, as well as increased IgG autoreactivity. These results need to be validated in a much larger sample of lupus patients studied longitudinally (over time) before these findings can be fully accepted and applied in the clinical setting.