Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
The Application of Protein Microarrays for Autoantibody Profiling in Morphea Patients
Kim1, Noori, Li2, Quan-Zhein, Jacobe3, Heidi
This study utilized protein microarray technology for large-scale analysis of autoantibodies in morphea to: (a) detect multiple autoantibodies in microliter volumes of serum, (b) identify autoantibody profiles specific to morphea, (c) and provide an efficient means to uncover novel antigens by testing the reactivity of morphea sera to candidate antigens.
Sera was utilized from 24 patients enrolled in the UTSW Medical Center Morphea Registry. All subjects had active disease and had not initiated therapy other than topical steroids. We compared the protein microarray signatures of morphea sera with non-immunologic and lupus erythematosus controls, matched for age, sex, and race. 16 new autoantigens were added to the previously published glomerular proteome array used for the evaluation of SLE activity. The added antigen specificities were incorporated based on literature searches linking the antigens to autoimmune sclerosing skin conditions. Manufacture, hybridization, and scanning of autoantigen microarrays and subsequent data analysis were performed according to the protocol previously published. (Clinical and Experimental Immunology. 147(2006):6070.)
Diagrams with row and column clustering were created with the Cluster and Treeview software (http://rana.lbl.gov/EisenSoftware.htm) and found that among the morphea sera, there was a tendency to group according to morphea subtypes, notably linear versus plaque type, for IgG, IgM, and IgA autoantibody profiling. When comparing morphea against SLE, the non-linear types, including plaque, generalized, and mixed, grouped with the SLE while linear morphea exhibited a distinct profile. Of the 92 autoantigens tested, contrary to previous reports, no significant increases were found in all subtypes of morphea of anti-singled stranded, anti-histone, and anti-topoisomerase antibodies. There was a trend toward an autoantibody reactivity pattern for the PDGFR alpha and beta autoantigen in morphea although not statistically significant (p>0.06). There was decreased IgG reactivity to aggrecan antibodies in morphea versus both normal and SLE controls (p=0.0052).
This study implies morphea subtypes display different autoimmune reactivity profiles across Ig subtypes, suggesting a disease specific signature. The reactivity intensities were greater for the IgG subclass than for IgM and IgA, providing insight into the pathogenesis of morphea on a molecular basis. Previously published data that suggested increased frequency of autoantibodies to single-stranded DNA, histones, and topoisomerase II-alpha in morphea were not duplicated in this larger cohort, while novel antigens like PDGF receptor had notable reactivity intensities in morphea. Protein microarrays for autoantibody profiling in morphea may allow for further characterization of this difficult disorder on a molecular level beyond the cutaneous lesions.
To cite this abstract, please use the following information:
Kim, Noori, Li, Quan-Zhein, Jacobe, Heidi; The Application of Protein Microarrays for Autoantibody Profiling in Morphea Patients [abstract]. Arthritis Rheum 2009;60 Suppl 10 :698