Apr. 20, 2012

Autoantibody Profiling in People with Lupus

Two major autoantibody clusters in systemic lupus erythematosus
Ching KH, Burbelo PD, Tipton C, Wei C, Petri M, Sanz I, and Iadarola MJ. (2012). PLoS One 7: e32001. [epub ahead of print]

What is the topic?

Measurement of autoantibodies can help not only in the diagnosis of lupus, but in some cases can also be useful in the tracking of disease activity over time, especially to monitor responses to drug treatment. In addition, some autoantibodies can be more useful in characterizing specific aspects of lupus than others. For example, antibodies to double-stranded DNA (anti-ds-DNA) and anti-Smith antibodies are useful in the diagnosis of lupus.

The variable and sometimes conflicting clinical associations reported for specific autoantibodies in people with lupus may occur due to differences in methods of detecting these autoantibodies. Simplification and standardization of such procedures may facilitate diagnosis, classification, therapeutic intervention, and prognosis in people with lupus.

What did the researchers hope to learn?

The researchers hoped to learn about whether their new methods for detecting lupus-related autoantibodies may be useful in characterizing and tracking disease-related outcomes in people with lupus.

Who was studied?

The study included 33 healthy people, as well as 205 people with lupus, recruited to the study from the Department of Rheumatology at the University of Rochester Medical Center and the Division of Rheumatology at Johns Hopkins University Medical Center. The participants were either part of the “pilot cohort” for initial testing or the “validation cohort” for validation of the initial results.

How was the study conducted?

The researchers used refined and advanced methods to detect several components of blood that are known to be associated with autoimmune responses in people with lupus. In addition, they used these methods to detect a combination of six of these in a single technique. These results were then used to relate specific lupus markers (found in the blood) to specific manifestations of lupus (such as that affecting the brain, kidneys, or skin). In additional studies, specific lupus markers were studied individually and related to specific manifestations of lupus.

What did the researchers find?

Initial studies showed that the advanced methods used here detected at least one significant (of six) “core” lupus markers (markers commonly found in people with lupus, such as lupus anticoagulant and anti-Smith antibodies) in 88% of lupus patients in the pilot cohort. These markers were detected across a wide range, with blood samples from many lupus patients showing 10-200 fold higher levels of these markers than found in healthy people.

Additional studies in the pilot cohort also showed that autoantibodies to four different kinds of interferon were present at significantly higher levels in people with lupus than in healthy people. Of these, antibodies to interferon-omega were the most common and were detected in 29% of the lupus patients. Importantly, several of the lupus patients in the pilot cohort had anti-interferon antibodies that were 100 times higher than found in healthy people. Overall, 42% of lupus patients had antibodies to at least one type of interferon.

When results of the core lupus markers from the pilot cohort were further analyzed and categorized based on specific sets of criteria, the lupus patients could be separated into two distinct groups or “clusters” based on their autoantibody profiles. In about 41% of lupus patients, antibodies to ribonuclear proteins (RNPs) and anti-Smith antibodies were most common. In another 47%, antibodies to RNA binding proteins and lupus anticoagulant were most common. Only a small subset of lupus patients (12%) could not be categorized into one of these two groups based on their autoantibody profiles.

Similar results were replicated in the validation cohort. Further analyses of results from the validation cohort showed that lupus patients having antibodies RNPs and anti-Smith antibodies as the most common had serositis (inflammation of the lining around organs such as the heart and lungs) more frequently. There were no further differences between clusters in terms of clinical manifestations of lupus, including lupus disease activity. When individual antibody types were evaluated relative to clinical manifestations of lupus, antibodies to a specific type of RNP (RNP-70k) were more commonly found in lupus patients with musculoskeletal manifestations while anti-Smith antibodies were more commonly found in lupus patients with cutaneous manifestations.

When autoantibody clusters were examined according to ethnicity, autoantibodies to RNPs and anti-Smith antibodies were more common in African-American than in Caucasian lupus patients. In addition, antibodies to interferon-omega were more common in African-Americans and Asians than in Caucasian lupus patients.

What were the limitations of the study?

Relatively little clinical data was available for the lupus patients included in this study. In addition, the researchers did not test many lupus markers in an organ-specific manner. Therefore, the researchers were limited in their ability to correlate autoantibody profiles with specific manifestations of lupus. Furthermore, these markers were not tested in people with other autoimmune diseases for purposes of comparison. Lastly, one of the autoantibody clusters identified in this study is similar to that previously found in Sjögren's syndrome patients.

What do the results mean for you?

These studies utilized innovative approaches to study several lupus markers in a single assessment. The results indicate that most lupus patients may be categorized into at least one of two groups with distinct autoantibody profiles which may be uniquely susceptible to different manifestations of lupus.

To confirm these results, further studies utilizing more patients from diverse ethnic backgrounds and with extensively documented clinical manifestations of lupus over time will be required. Ideally, comparison of these results from lupus patients to those of Sjögren's syndrome patients or patients with other autoimmune diseases (likely in terms of genetics) could help to differentiate these patient populations in terms of the autoantibody clusters studied here.

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