Catalytic antibodies in patients with systemic lupus erythematosus

Abstract

Objective: Antibodies with catalytic (hydrolytic) properties to DNA or RNA have been reported in systemic lupus erythematosus (SLE). However, it is well known that ethnicity plays an important role in the presentation of SLE and severity of the disease; hence, these data may not truly represent a general feature of all SLE patients. Therefore, we have analyzed the hydrolyzing activity of immunoglobulin G (IgG) of SLE patients from the Indian population with an aim to decode whether the catalytic antibody response represents part of an active disease process.

Methods: IgGs were isolated from the sera of 72 consecutive patients diagnosed with SLE. As a control, IgGs from healthy donors were used. The catalytic activity of IgG was measured by PFR-MCA and affinity-linked oligonucleotide nuclease assay.

Results: IgGs from patients with SLE from the Indian subcontinent displayed significantly higher hydrolysis rates of both the surrogate substrate, PFR-MCA, and the DNA than IgG from healthy individuals. Intergroup comparisons of the IgG-PFR-MCA interactions with clinical manifestations of the disease demonstrated a significantly increased level of hydrolysis among the patients with renal involvement who tested positive for anti-dsDNA antibodies. The PFR-MCA hydrolysis also appears to be associated with the active disease (p=0.0988, vs. inactive group).

Conclusion: The prevalence of catalytic antibodies represents a general feature of SLE patients, irrespective of their origin.

Figure 1

Rates of the PFR-MCA hydrolysis (μmol/min/mol, mean±SD) by IgG of z72 patients with SLE and 45 healthy controls (normal). The mean (±SD) hydrolysis in the normal group was 31.03 (±28.92) μmol/min/mol, whereas in patients with SLE, it was 56.62 (±44.41) μmol/min/mol. The statistical significance as determined by the Mann-Whitney U-test is indicated.

Figure 2

Relationship between the SLE patients’ IgG-mediated hydrolysis of PFR-MCA (μmol/min/mol, mean±SD) and clinical manifestations. The number of patients in each category is indicated. The mean and SD values of PFR-MCA for IgG from the normal individuals are also marked. Statistical significance as determined by the Mann-Whitney U-test is indicated.

Figure 3

Correlation between the SLE patients’ IgG-mediated PFR-MCA hydrolysis (μmol/min/mol) and SLEDAI scores of 72 patients with SLE, as determined by the Pearson correlation test.

Figure 4. a, b

Hydrolysis of DNA (mean±SD) by IgG in patients with SLE [30 active cases of SLE who were under the steroid therapy for <12 months, classified into anti-dsDNA-positive (n=24) or -negative (n=6), and healthy controls (normal, n=30)]. The statistical significance as determined by the Mann-Whitney U-test is indicated (a); Correlation between the DNA hydrolysis by IgGs of patients with SLE (30 active cases of SLE who were under the steroid therapy for <12 months) and the SLEDAI score of patients, as determined by the Pearson correlation test (b).

Figure 5

DNA hydrolysis by IgG purified from patients with SLE [active vs. inactive; lupus nephritis (LN) vs. non-LN] who were under the steroid therapy for <12 months (n=30). The values are depicted as box plots, where the boxes represent the 25th–75th percentiles, and the lines within the boxes represent the median. The statistical significance as determined by the Mann-Whitney U-test is indicated.