Background/Purpose:

Systemic lupus erythematosus (SLE) affects various body organs making its clinical presentation highly variable. While previous studies have demonstrated associations between lab abnormalities and individual clinical manifestations of disease, our study aimed to be more specific and categorized patients into sub-groups based on their unique presentations. We then investigated associations between immunological/serological abnormalities and exclusive clinical phenotypes of SLE.

Methods:

Information regarding SLE related clinical symptoms and serological data were collected from 201 patients diagnosed with SLE. Laboratory abnormalities included: anti-nuclear antibody (Ab), anti-Ro Ab, anti-La Ab, anti-Smith Ab, anti-U1-ribonucleoprotein Ab, anti-rheumatoid factor Ab, anti-dsDNA Ab, low C3, low C4, anti-cardiolipin Ab, lupus anticoagulant and beta2-glycoprotein. Patients were classified into clinical subgroups based on manifestation(s) of disease: arthritis alone (A); mucocutaneous disease alone (B); nephritis alone (C); arthritis + mucocutaneous disease (D); arthritis + nephritis (E); nephritis + mucocutaneous disease (F); or all 3 (G). Omnibus chi-square tests evaluated associations between individual lab abnormalities and phenotype with subsequent post-hoc evaluation for significant omnibus tests. Positive and negative predictive values (PPV, NPV) were also investigated.

Results:

Analyses revealed that anti-Smith, anti-dsDNA antibodies and low levels of C3 and C4 were associated with phenotype G (p=0.001, Chi-square (χ²)=11.3; p=0.004, χ²=8.3; p<0.0001, χ²=21.4; p<0.0001, χ²=22.5 respectively) with a PPV of 59.4%, 85.3%, 91.2% and 85.3% respectively, and anti-Sm Ab had a NPV of 71.3%. Anti-dsDNA Ab, low C3 and C4 levels were additionally significantly associated with phenotype F (p=0.01, χ²= 6.25; 0.01, χ²=6.48; p=0.01, χ²=6.54 respectively). PPV of anti-dsDNA Ab, low C3 and C4 for F was 93.3%, 91.2%, and 80% respectively and 73.3% combined. Further, anti-ds-DNA Ab, low C3 and C4 were negatively associated with phenotype B (p<.001, χ²= 15.3; p<.001, χ²=12.48; p=.014, χ²=6.1, respectively). Low complement levels were also negatively associated with phenotype D (C3: p=.038, χ²=4.3; C4: p=.011, χ²= 6.54). While nephritis alone was not significantly associated with any markers, anti-dsDNA Ab, and low complement levels combined had an 80.8% NPV for renal disease.

Conclusion:

Our results suggest that an expanded epitope including anti-dsDNA and anti-Smith antibodies, along with low complement levels are associated with a broader phenotype in SLE which includes arthritis, nephritis and mucocutaneous involvement. Anti-dsDNA Ab and low complement levels were also associated with the mucocutaneous disease and nephritis combined but not nephritis or mucocutaneous disease alone. In fact, these serological markers were negatively associated with mucocutaneous involvement. These findings suggest that immunological profiles may reflect unique phenotypes of SLE. Future genetic models that target particularphenotypes of SLE and associated immunologic abnormalities may be useful in developing new drug therapies.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/associations-between-standard-serological-markers-and-different-clinical-phenotypes-in-systemic-lupus-erythematosus/