Diagnostic Tests for SLE Should Include New Variants Found in African Patients, Study Suggests

Black Africans often have distinct variants of systemic lupus erythematosus compared to white patients, but conventional diagnostic tests can’t detect these variants, say researchers from Scotland’s University of Edinburgh and collaborators from Zimbabwe.

Their findings point up the urgency of including specific tests to identify these disease variants, improving diagnosis and treatment.

“For the first time, we have highlighted the importance of two variants of systemic lupus that affect black Africans, including one which was previously not defined in detail. Thanks to our research, we also have the means to diagnose and distinguish them,” Francisca Mutapi, PhD, professor at the School of Biological Sciences and corresponding author of the study, said in a press release.

The study, “Evidence of a distinct group of Black African patients with systemic lupus erythematosus,” appeared in BMJ Global Health.

SLE, a chronic autoimmune disease, is marked by several symptoms including pain, fatigue, depression and impaired cognition. These symptoms can significantly affect patients’ quality of life and productivity.

The condition is more common among people of African descent — particularly southern Africa, where morbidity and mortality rates are relatively compared to other populations, mostly due to poor and late diagnosis.

Conventional SLE diagnostic tests, such as the antinuclear antibody (ANA) reactivity test – which analyzes production of auto-antibodies against proteins found in the cell’s nuclei — were developed based on non-African populations.

Researchers sought to compare results from the ANA reactivity test in a population of black African patients to their SLE clinical presentation.

The retrospective study enrolled 61 SLE patients and 100 healthy controls between the ages of 1 and 81 years. Scientists analyzed patients’ serum to determine autoantibody reactivity to several antigens, including the proliferating cell nuclear antigen (PCNA), the double-stranded DNA (dsDNA) and the anti-mitochondrial antibody M2 (AMA-M2).

As expected, 97 percent of SLE patients showed signs of autoantibody reactivity, compared to only 15 percent of controls.

Likewise, 41 percent of all SLE patients tested showed autoantibody reactivity against the dsDNA antigen, which is more frequent among people with classical disease symptoms, such as painful joints, and is normally included in the standard diagnostic tests for lupus.

The second, larger group of patients (54%) showed autoantibody reactivity against the PCNA antigen. Interestingly, reactivity against PCNA and dsDNA were mutually exclusive, suggesting they identified two distinct subgroups of patients with African SLE patients.

Researchers then found that patients with antibodies against both PCNA and AMA-M2 were nine times more likely to experience only skin-related symptoms than other SLE patients. But tests against PCNA and AMA-M2 reactivity are not included in the conventional diagnostic tests for lupus.

These findings strongly suggest that relying on conventional diagnostic tests may not be the best strategy for patients in Africa. The team believes adding anti-PCNA antibodies to standard ANA tests would not only help diagnose and speed up treatment for patients but could also be used as a biomarker to identify SLE disease variants that only affect the skin.

“Our study shows a need to (i) widen the panel of diagnostic antinuclear and anti-mitochondrial antigens used in African patients; (ii) further refine the predictive values of the ANA reactivity to different nuclear and mitochondrial antigens in order to differentiate SLE syndromes in African populations; and (iii) consider anti-PCNA reactivity, which has so far been largely excluded in Africa and elsewhere, as a diagnostic marker for patients with SLE,” researchers wrote.