Background SLE is associated with a large spectrum of autoantibodies, but currently there is no serologic diagnosis. Each autoantibody individually fails to discriminate with sufficient specificity and/or sensitivity SLE patients from healthy controls or from subjects afflicted with other autoimmune diseases. Currently a diagnosis of SLE is based on multiple criteria and can take years of concerned monitoring.
Objectives We developed the previously described iCHIP™1 as an effective SLE rule-out diagnostic test by profiling with an antigen microarray multiple, distinct autoantibody reactivities in the sera of SLE patients compared to healthy controls and by using informatics analysis to rule out a diagnosis of SLE. An initial set of 200 antigens associated with SLE was selected from the literature bolstered with sets of proprietary markers developed by ImmunArray. Here we report verification and validation of our SLE-Key™ Rule-Out Serologic Test.
Methods We collected serum samples from 250 SLE patients from four independent sources [Albert Einstein College of Medicine, Medical University of South Carolina, Johns Hopkins University and Emory University] and compared them with sera of 250 healthy control samples independently sourced. We tested these samples using the ImmunArray iCHIP™ - a proprietary microarray that displays multiple antigens representing a range of SLE-associated biochemical pathways. Training was performed on a subset of 150 SLE patients and 150 healthy controls using 4 independent classification methods. Verification was performed on an additional set of 50 SLE patients and 50 healthy control samples.
Results All 4 classification methods differentiated SLE patients from healthy subjects with a sensitivity of greater than 90% and specificity of greater than 70% using a selected subset of auto-antigens. The informative antigens represented some known to be associated with SLE, as well as some not previously known to have an association with the disease. Validation of the different classification methods was performed on the remaining set of 50 SLE patients and 50 healthy controls.
Conclusions The SLE Key multiplex test can be used to assist physicians in ruling out serologically a diagnosis of SLE with a sensitivity of >90%. Work comparing this testing performance in direct comparison to standard serologic testing is ongoing.
Fattal, I, et al; Immunology 2010, 130, 337-343
Acknowledgements The authors wish to acknowledge the invaluable contributions of Ornit Cohen-Gindi, Miriam Lerner, Naama Shefer, Ilana Gilkaite, Angela Turner, Janice Jesse, and Nazanin Mishrani
Disclosure of Interest I. Cohen Shareholder of: Shareholder in ImmunArray, Grant/research support from: Grant Research Support, Consultant for: Consultant of ImmunArray, C. Putterman Consultant for: Consultant of ImmunArray, N. Jordan: None declared, K. Jakobi Employee of: Employee of ImmunArray, R. Sorek Employee of: Employee of ImmunArray, Y. Blumenstein: None declared, S. Batty Shareholder of: Shareholder in ImmunArray, Employee of: Employee of ImmunArray