Evidence of a distinct group of Black African patients with systemic lupus erythematosus

Abstract

Background: The autoimmune disease systemic lupus erythematosus (SLE) occurs more frequently in patients of African descent with high morbidity and mortality. Current SLE diagnostic criteria including antinuclear antibody (ANA) reactivity are derived largely from non-African populations. This study characterises ANA reactivity patterns and relates them to SLE clinical presentation in Black African patients.

Methods: Sera from Black participants (61 patients with SLE and 100 controls) aged 1-81 years were analysed for reactivity against the antigens: uridine 1-ribonuclear protein, Smith uridine-1-5 ribonuclear protein antigen, soluble substance-A, recombinant Ro-52, soluble substance-B, Scl-70, cytoplasmic histidyl-tRNA synthetase antigen, proliferating cell nuclear antigen (PCNA), nucleosomes, ribonuclear P-protein, antimitochondrial antibody M2 (AMA-M2), histones, double-stranded DNA (dsDNA), centromere protein B and polymyositis-sclerosis overlap antigen.

Findings: A significantly higher proportion (97%) of the 61 patients with SLE had detectable autoantibody reactivity compared with 15% of the 100 controls (p<0.001). The highest frequencies of autoantibody reactivity in patients with SLE were against the dsDNA antigen (41%) and PCNA (54%). Anti-PCNA and anti-dsDNA reactivity were mutually exclusive (p<0.001) giving rise to two distinct groups of Black African patients with SLE. The first group (n=25) had reactivity profiles consistent with international standard SLE definitions, including anti-dsDNA reactivity, and was 13 times more likely to present with joint symptoms. The larger, second group (n=34), characterised by anti-PCNA and anti-AMA-M2 reactivity, was nine times more likely to present with only cutaneous symptoms.

Interpretation: Our study demonstrates a need to extend autoantibody panels to include anti-PCNA in the diagnostic process of Black African patients and further refine the predictive values of the reactivity to different antigens to differentiate SLE syndromes in African populations.

Keywords: elisa; public health; screening; serology.

Figure 1

Photographs of patients’ physical symptoms. (A) Non-scarring, non-atrophic patchy hair loss, alopaecia areata in a 14-year-old boy with SLE (dsDNA+). (B) Diffuse thinning and loss of hair in a 45-year-old woman (dsDNA+). (C) A 36-year-old woman with a rash involving the malar area and nose, sparing the naso-labial folds (SLE butterfly rash) (dsDNA−; PCNA−). (D) A 54-year-old woman with scaring alopaecia of the scalp, and scaring lesions on the ear lobes and parts of the face (PCNA+). (E) A 13-year-old girl with non-scarring photosensitive dermatitis of the neck and face (PCNA+). dsDNA, double-stranded DNA; PCNA, roliferating cell nuclear antigen; SLE, systemic lupus erythematosus.

Figure 2

Proportion of participants diagnosed with SLE (n=61) and study control patients (n=100) who are reactive against each antinuclear antigens. AMA-M2, antimitochondrial antigen M2; CENP-B, centromere protein B; dsDNA, double-stranded DNA; Jo-1, cytoplasmic histidyl-tRNA synthetase antigen; nRNP/Sm, uridine 1-ribonuclear protein; PCNA, proliferating cell nuclear antigen; PM-Scl, polymyositis–sclerosis overlap antigen; Rib. P-protein, ribosomal P protein; Ro-52, recombinant Ro-52; SLE, systemic lupus erythematosus; Sm, Smith uridine-1-5 ribonuclear protein antigen; SS-A, soluble substance-A; SS-B, soluble substance-B.

Figure 3

Figure showing the tetrachoric correlation coefficients for nine dichotomous autoantibodies with reactivity frequency >5% among the patients with SLE (n=61). AMA-M2, antimitochondrial antigen M2; dsDNA, double-stranded DNA; nRNP/Sm, uridine 1-ribonuclear protein; PCNA, proliferating cell nuclear antigen; Ro-52, recombinant Ro-52; SLE, systemic lupus erythematosus; Sm, Smith uridine-1-5 ribonuclear protein antigen; SS-A, soluble substance-A.

Figure 4

Two-way cluster analysis dendogram of patients with SLE (n=59, with two patients showing no ANA subtype reactivity excluded). Only the ANA subtypes with reactivity >5% reactivity frequency were included. The matrix of shaded squares represents the patient ×ANA reactivity matrix, while the dendrograms show the clustering. The dendrograms are scaled by Wishart’s objective function, expressed as the percentage of information remaining at each level of grouping. Each square represents the presence (black) and absence (white) of a reaction with a given biomarker. Two main clusters (designated 1 and 2) were identified. Matrix also indicates the presence of clinical symptoms with the colour key: blue=cutaneous symptoms; green=joint symptoms; purple=asthma and rhinitis-like symptoms; turquoise=gastrointestinal symptoms; yellow=other symptoms. AMA-M2, antimitochondrial antigen M2; ANA, antinulcear antibody; dsDNA, double-stranded DNA; nRNP/Sm, uridine 1-ribonuclear protein; PCNA, proliferating cell nuclear antigen; Ro-52, recombinant Ro-52; SLE, systemic lupus erythematosus; Sm, Smith uridine-1-5 ribonuclear protein antigen; SS-A, soluble substance-A.

Figure 5

Comparison of reactivity frequency between patients with SLE and published reference ranges. Mean proportion of patients (n=61) positive for reactivity against the 15 ANA subtypes along with their exact 95% CIs. Data for the patients were divided into the two clusters identified in figure 4. Cluster 1 (blue) includes patients reacting primarily to dsDNA. Cluster 2 (red) includes patients reacting primarily with PCNA. Proportion of the reference population (recognised criteria11 23–26) is in black. Reference values: dots represent only a single value found for reference ANA frequency; bars represent lowest and highest in the range of values found for the reference. AMA-M2, antimitochondrial antigen M2; ANA, antinulcear antibody; CENP-B, centromere protein B; dsDNA, double-stranded DNA; Jo-1, cytoplasmic histidyl-tRNA synthetase antigen; nRNP/Sm, uridine 1-ribonuclear protein; PCNA, proliferating cell nuclear antigen; PM-Scl, polymyositis–sclerosis overlap antigen; Rib. P-protein, ribosomal P protein; Ro-52, recombinant Ro-52; SLE, systemic lupus erythematosus; Sm, Smith uridine-1-5 ribonuclear protein antigen; SS-A, soluble substance-A; SS-B, soluble substance-B.