Originally published in SLE in Clinical Practice, September 1999, Vol. 2, Issue 3, a publication of the Lupus Foundation of America, Inc.

Why does lupus discriminate by ethnicity?

One of the disturbing mysteries of systemic lupus erythematosus (SLE) is that it differentially affects patients by ethnic group. Why do ethnic minorities such as Hispanics and African-Americans experience more active, aggressive lupus? Why are these groups younger when the symptoms appear? Why do the symptoms appear so suddenly?

In 1993 a request for an application to study lupus in minority populations was released by NIAMS, the National Institute of Arthritis and Musculoskeletal and Skin Disorders. Investigators from three institutions teamed up to study the relative contribution of genetic and socioeconomic factors on the course and outcome of lupus in Hispanics, African-Americans, and Caucasians in Texas and Alabama. This project became LUMINA (an acronym for LUpus in MInority populations: NAture vs. nurture), a comprehensive database of information about patients with lupus.

Enrolling participants

For the first cycle of funding, 229 patients with systemic lupus were recruited by investigators from the University of Alabama at Birmingham, the University of Texas Health Science Center at Houston, and the University of Texas Medical Branch at Galveston. To participate in LUMINA, individuals had to meet criteria for the classification of lupus (as defined by the American College of Rheumatology or ACR); have disease of five or less years in duration; and be of the same ethnicity as their four grandparents. Realizing the complexities associated with ethnicity, the Hispanic group was limited to patients of Mexican-American or Central-American ancestries.

At the time patients entered the LUMINA study, a thorough evaluation was conducted by a study physician. After this initial, or baseline, visit, patients were scheduled for a study visit every six months until the second year of follow-up, and then yearly thereafter.

A very important issue for patients with lupus is the outcome of their disease. Several instruments were used to examine disease outcome: the SLAM (Systemic Lupus Activity Measure) for disease activity; the SDI (SLICC/ACR Damage Index) for disease damage; the SF-36 (Short Form-36) for patient function. Mortality rates also were documented.

Categories of data being collected

Besides disease outcome, the LUMINA study has compiled data regarding various characteristics: socioeconomic-demographic (age, gender, marital status, income, occupation, health insurance, access to health care, health care utilization, housing, and personal habits); clinical attributes (disease onset type, disease duration, clinical manifestations, number of ACR criteria, co-morbidities, treatments); and behavioral and psychosocial constructs (social support, abnormal illness-related behaviors, helplessness, and acculturation-Hispanics only). Also being studied are immunologic profiles (autoantibodies) and immunogenetic profiles [MHC (HLA)-Class II (DR, DP and DQ) genotypes and MHC-Class III (C4) allotypes].

The baseline data have been published, and data up through two years of follow-up have been presented at national and international meetings. The three-year data have been analyzed for presentation at the 1999 national meetings.

Study findings to date

In short, and as expected, lupus patients of Hispanic and African-American ethnicity have more active disease at baseline, as well as at the time of diagnosis. Although patients from all three groups had a comparable number of ACR criteria, African-Americans and Hispanics had more serious organ system involvement than Caucasians. Caucasians, on the other hand, enjoyed a better socioeconomic status and were, by and large, older than patients in the two minority groups.

As for the role of immunogenetics in lupus, at disease onset some of the immunogenetic markers were associated with specific disease symptoms (such as renal disease) and/or overall disease activity. However, at baseline and subsequent visits these variables no longer were predictive of disease manifestations or disease activity. Instead, variables such as abnormal illness-related behaviors emerged as important predictors. Furthermore, some of the predictors were valid across ethnic groups, whereas others were valid for a given ethnic group only.

At entry into the study, disease damage was comparable for patients in the three ethnic groups. However, as time passed, the total damage became worse for the two minority groups than for the Caucasians, although the differences were not statistically significant.

Preliminary analyses of two- and three-year data have shown that the main predictor of overall disease damage as measured by the SDI is disease activity over time. African-Americans and Hispanics have accrued more renal damage (renal failure and/or proteinuria) than Caucasians. African-Americans have accrued skin damage (scarring alopecia) more rapidly than either Hispanics or Caucasians.

Disease activity also has emerged as an important predictor of death for this group of patients. Consistent with lower disease activity, Caucasians exhibited lower mortality rates than Hispanics or African-Americans.

An unexpected finding has been that patients with SLE are significantly impaired both physically and mentally, as demonstrated by the physical and mental capacity measures of the SF-36. Even more unexpected is the realization that these impairments are related not so much to the degree of disease activity and damage accrued, but to psychosocial constructs such as abnormal illness-related behaviors and/or insufficient social support.

Thus far the LUMINA study has shown that Hispanic lupus patients experience more active and serious disease than Caucasians, but probably not worse than African-Americans, the largest minority group in the U.S.

The LUMINA findings have prompted the investigators to reexamine the model initially formulated to explain outcome in SLE (Figures 1a and 1b).

What the future holds for LUMINA

At the present time, follow-up is being conducted of the members of the original cohort. At the same time, new members are being added to compensate for the losses experienced with the initial cohort members (due to deaths, refusals, or loss-of-contact).

The combined, comprehensive database of the original and additional members of the LUMINA cohort constitutes an invaluable repository of data for which many more questions can be formulated. Banking DNA from these subjects will allow the examination of other genetic markers that have been or may be discovered to influence disease outcome in lupus. These data, in conjunction with meticulously gathered clinical, sociodemographic and psychosocial information, as well as a serum repository, places the LUMINA project in an advantageous situation for studying lupus in the years to come. The results of the LUMINA study certainly will have relevance in developing therapeutic interventions for patients who may share comparable outcomes.

Graciela S. Alarcón, M.D., M.P.H., is currently the Jane Knight Lowe Professor of Medicine in Rheumatology at the University of Alabama in Birmingham. Dr. Alarcón received her Master's degree in Public Health from Johns Hopkins University in Baltimore, MD, and her medical degree from Universidad Peruana Cayetano Heredia, in Lima, Peru. She has been at the University of Alabama in the Division of Clinical Immunology and Rheumatology since 1980. In 1997 Dr. Alarcón received the Virginia Engalichteff Award for Impact on Quality of Life from the Arthritis Foundation. She presently serves on the editorial boards of Arthritis and Rheumatism, The Journal of Rheumatology, Lupus, and Balières Clinical Rheumatology, and is Editor-in-Chief of RA Index and Reviews.

Dr. Alarcón's co-authors for this article are Kemi Brooks, M.P.H., LUMINA Project Coordinator at the University of Alabama-Birmingham; John D. Reveille, M.D., the George S. Bruce Jr. Professor of Arthritis and other Rheumatic Diseases at the University of Texas Health Science Center-Houston; and Jeffrey R. Lisse, M.D., Professor of Medicine and Pathology at the University of Texas Medical Branch-Galveston.

 © 1999 Lupus Foundation of America, Inc.

Disclaimer: The opinions and statements expressed by the authors or contributors to this publication do not necessarily reflect the opinions or positions of the Lupus Foundation of America, Inc.

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