Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis

Abstract

The objective of this paper is to investigate the association between patterns of anti-dsDNA antibody isotypes and specific clinical manifestations (categorized in renal, musculoskeletal, cutaneous, hematological, pulmonary, neurological and cardiac). Sera of 202 systemic lupus erythematosus (SLE) patients, 33 patients suffering from other autoimmune diseases and 115 healthy blood donors were analysed for anti-dsDNA antibodies by IgG-, IgA- and IgM-specific ELISA, Farr-assay and CLIF. A subset of 24 SLE patients was investigated in a longitudinal study over a period of one to six years. Disease activity of 105 SLE patients was measured according to the ECLAM score. In the cohort of SLE patients 63% were positive for the IgG class, 40% for the IgA and 57% for the IgM class specific anti-dsDNA ELISA. Sensitivity (79%) and specificity (99%) for the diagnosis of SLE appeared to be highest for the ELISA measuring all isotypes of anti-dsDNA antibodies. The concentrations of anti-dsDNA isotypes showed a strong correlation with disease activity. Analysing the relationship between IgG, IgA and IgM anti-dsDNA antibody isotypes and clinical manifestation, we found a significant association of the IgM isotype with cutaneous involvement and of the IgG isotype with lupus nephritis. The IgG/IgM ratio of anti-dsDNA antibodies represented a significant parameter to distinguish patients with lupus nephritis from those without renal involvement. In the longitudinal study, a continuous ratio under 0.8 was associated with absence of renal involvement throughout the investigated period. In conclusion, the evaluation of anti-dsDNA isotypes provides a diagnostic tool to define subsets within SLE patients with different clinical manifestations. In particular, the IgG/IgM ratio of anti-dsDNA antibodies could be used as a prognostic marker for lupus nephritis during the course of the disease.

Protective autoantibodies: Role in homeostasis, clinical importance, and therapeutic potential

“…In a recent study, absence of lupus nephritis was suggested to be a consequence of a predominance of the IgM isotype of anti-dsDNA antibodies (25). SLE patients with a permanent ratio of IgG to IgM of Ͻ0.8 did not develop lupus nephritis, despite high levels of antidsDNA antibodies.…”

Outcomes in patients with systemic lupus erythematosus with and without a prolonged serologically active clinically quiescent period

“…Anti-double-stranded DNA (anti-dsDNA) antibodies are recognized as highly specific diagnostic markers for SLE, are found in 60 -80% of patients (1)(2)(3), and have been included in the American College of Rheumatology (ACR) classification criteria since 1982 (4,5). Anti-dsDNA antibodies have been observed to be strongly correlated with SLE for more than 50 years.…”

“…In 2006, Prasad et al found that the presence of anti-dsDNA antibodies as measured at 2 consecutive visits was not predictive of damage at 5 years (43), which is certainly consistent with our findings in SACQ patients. The relative pathogenicity of anti-dsDNA antibody isotypes is now appreciated, with anti-dsDNA IgG, specifically IgG2 and IgG3, found to be most pathogenic, perhaps owing to a propensity to activate complement or engage Fc receptors (1,2,30,44,45). We believe a particular strength of this study lies in the use of the Farr assay to detect anti-dsDNA antibodies, as it has been found to preferentially bind high-avidity antibodies and to be best correlated with global disease activity, as well as renal and vasculitic involvement (1,46).…”

“…The relative pathogenicity of anti-dsDNA antibody isotypes is now appreciated, with anti-dsDNA IgG, specifically IgG2 and IgG3, found to be most pathogenic, perhaps owing to a propensity to activate complement or engage Fc receptors (1,2,30,44,45). We believe a particular strength of this study lies in the use of the Farr assay to detect anti-dsDNA antibodies, as it has been found to preferentially bind high-avidity antibodies and to be best correlated with global disease activity, as well as renal and vasculitic involvement (1,46). Therefore, further characterization of anti-dsDNA antibodies by isotype and the search for alternate biomarkers such as anti-␣-actinin and antinucleosome antibodies may yield novel methods for identifying and/or predicting disease flare in SACQ patients, and perhaps in all lupus patients (47)(48)(49)(50)(51).…”

B-cell-targeted therapies in systemic lupus erythematosus and ANCA-associated vasculitis: current progress

“…The prevalence of these auto-antibodies varies and may be associated with individual manifestations of SLE. For instance, antibody to dsDNA antibodies which is present in 30%-70% of the serology of SLE patients correlates with the development and progression of glomerulonephritis [11] whereas antibody to Ro is associated with photosensitivity [12].…”